Updated on 2024/04/26

写真a

 
NISHITA Michiru
 
Organization
School of Medicine (Life Sciences and Social Medicine) Department of Biochemistry Professor
Title
Professor
Contact information
メールアドレス

Degree

  • 博士(薬学) ( 2000.3   北海道大学 )

Research Interests

  • Wntシグナル

  • がん浸潤・転移

  • 細胞極性

  • cell biology

Research Areas

  • Life Science / Medical biochemistry

  • Life Science / Cell biology

  • Life Science / Developmental biology

Research History

  • 福島県立医科大学医学部・教授

    2019.7 - Now

  • 神戸大学大学院医学研究科・准教授

    2007.10 - 2019.6

  • 神戸大学大学院医学系研究科・助教

    2007.4 - 2007.9

  • 神戸大学大学院医学系研究科・助手

    2004.4 - 2007.3

  • オランダ癌研究所・博士研究員

    2001.10 - 2002.5

  • 日本学術振興会・特別研究員 (PD)(東北大学大学院生命科学研究科)

    2001.4 - 2004.3

  • 東北大学大学院理学研究科・博士研究員

    2000.4 - 2001.3

▼display all

Professional Memberships

  • 日本生化学会

  • 日本分子生物学会

  • 日本癌学会

  • 日本分子生物学会

Papers

  • miR-200c-141 induces a hybrid E/M state and promotes collective cell migration in MDA-MB-231 cells.

    Nagai T, Sato M, Nishita M

    Biochemical and biophysical research communications   709   149829   2024.5( ISSN:0006-291X

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    DOI : 10.1016/j.bbrc.2024.149829

    PubMed

  • Role of the Ror family receptors in Wnt5a signaling.

    Kamizaki K, Minami Y, Nishita M

    In vitro cellular & developmental biology. Animal   2024.4( ISSN:1071-2690

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    DOI : 10.1007/s11626-024-00885-4

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  • Rho family small GTPase Rif regulates Wnt5a-Ror1-Dvl2 signaling and promotes lung adenocarcinoma progression

    Michiru Nishita, Koki Kamizaki, Kyoka Hoshi, Kana Aruga, Ikumi Nishikaku, Hiroshi Shibuya, Kunio Matsumoto, Yasuhiro Minami

    Journal of Biological Chemistry   299 ( 10 )   105248 - 105248   2023.9( ISSN:0021-9258

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1016/j.jbc.2023.105248

    PubMed

  • c-Src-mediated phosphorylation and activation of kinesin KIF1C promotes elongation of invadopodia in cancer cells

    Takeshi Saji, Michiru Nishita, Kazuho Ikeda, Mitsuharu Endo, Yasushi Okada, Yasuhiro Minami

    Journal of Biological Chemistry   298 ( 7 )   102090 - 102090   2022.7( ISSN:0021-9258

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1016/j.jbc.2022.102090

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  • Autonomous and intercellular chemokine signaling elicited from mesenchymal stem cells regulates migration of undifferentiated gastric cancer cells.

    Daiki Okamoto, Natsuko Yamauchi, Gosuke Takiguchi, Michiru Nishita, Yoshihiro Kakeji, Yasuhiro Minami, Koki Kamizaki

    Genes to cells : devoted to molecular & cellular mechanisms   27 ( 5 )   368 - 375   2022.3( ISSN:1356-9597

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1111/gtc.12933

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  • Characterization of morphological alterations in micropapillary adenocarcinoma of the lung using an established cell line.

    Sonoda D, Kamizaki K, Matsuo Y, Aruga K, Mikubo M, Yamashita K, Nishita M, Minami Y, Satoh Y

    Oncology reports   47 ( 1 )   2022.1( ISSN:1021-335X

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    DOI : 10.3892/or.2021.8230

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  • 雄の外生殖器形成過程でWnt5aにみられる、各発生段階に応じた様々な機能(Stage-dependent function of Wnt5a during male external genitalia development)

    Alcantara Mellissa C., Suzuki Kentaro, Acebedo Alvin R., Sakamoto Yuki, Nishita Michiru, Minami Yasuhiro, Kikuchi Akira, Yamada Gen

    Congenital Anomalies   61 ( 6 )   212 - 219   2021.11( ISSN:0914-3505

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  • Stage-dependent function of Wnt5a during male external genitalia development.

    Alcantara MC, Suzuki K, Acebedo AR, Sakamoto Y, Nishita M, Minami Y, Kikuchi A, Yamada G

    Congenital anomalies   61 ( 6 )   212 - 219   2021.7( ISSN:0914-3505

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    DOI : 10.1111/cga.12438

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  • Oncogenic E6 and/or E7 proteins drive proliferation and invasion of human papilloma virus‑positive head and neck squamous cell cancer through upregulation of Ror2 expression.

    Mehmet Ozgur Avincsal, Koki Kamizaki, Naoe Jimbo, Hirotaka Shinomiya, Ken-Ichi Nibu, Michiru Nishita, Yasuhiro Minami

    Oncology reports   46 ( 1 )   2021.7( ISSN:1021-335X

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    DOI : 10.3892/or.2021.8099

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  • 間葉系幹細胞に由来するCXCL16はSTAT3が媒介するRor1発現によって胃癌細胞の進行を促進する(Mesenchymal stem cell-derived CXCL16 promotes progression of gastric cancer cells by STAT3-mediated expression of Ror1)

    Ikeda Taro, Nishita Michiru, Hoshi Kyoka, Honda Takashi, Kakeji Yoshihiro, Minami Yasuhiro

    Cancer Science   111 ( 4 )   1254 - 1265   2020.4( ISSN:1347-9032

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  • 癌浸潤の戦術 孤立性浸潤と集団性浸潤(Tactics of cancer invasion: solitary and collective invasion)

    Nagai Tomoaki, Ishikawa Tomohiro, Minami Yasuhiro, Nishita Michiru

    The Journal of Biochemistry   167 ( 4 )   347 - 355   2020.4( ISSN:0021-924X

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  • Mesenchymal stem cell-derived CXCL16 promotes progression of gastric cancer cells by STAT3-mediated expression of Ror1.

    Ikeda T, Nishita M, Hoshi K, Honda T, Kakeji Y, Minami Y

    Cancer science   111 ( 4 )   1254 - 1265   2020.2( ISSN:1347-9032

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1111/cas.14339

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  • Tactics of cancer invasion: solitary and collective invasion.

    Nagai T, Ishikawa T, Minami Y, Nishita M

    Journal of biochemistry   167 ( 4 )   347 - 355   2020.1( ISSN:0021-924X

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1093/jb/mvaa003

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  • 浸潤突起形におけるKIF1Cの機能

    佐事武, 西田満, 西田満, 遠藤光晴, 岡田康志, 岡田康志, 岡田康志, 南康博

    日本分子生物学会年会プログラム・要旨集(Web)   43rd   2020

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    J-GLOBAL

  • Impaired ligand-dependent MET activation caused by an extracellular SEMA domain missense mutation in lung cancer.

    Miao W, Sakai K, Sato H, Imamura R, Jangphattananont N, Takagi J, Nishita M, Minami Y, Matsumoto K

    Cancer science   110 ( 10 )   3340 - 3349   2019.10( ISSN:1347-9032

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    DOI : 10.1111/cas.14142

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  • 肺癌において細胞外SEMAドメインにあるミスセンス突然変異によって生じるリガンド依存性MET活性化の障害(Impaired ligand-dependent MET activation caused by an extracellular SEMA domain missense mutation in lung cancer)

    Miao Wenyu, Sakai Katsuya, Sato Hiroki, Imamura Ryu, Jangphattananont Nawaphat, Takagi Junichi, Nishita Michiru, Minami Yasuhiro, Matsumoto Kunio

    Cancer Science   110 ( 10 )   3340 - 3349   2019.10( ISSN:1347-9032

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  • Intraflagellar transport 20 promotes collective cancer cell invasion by regulating polarized organization of Golgi-associated microtubules.

    Aoki T, Nishita M, Sonoda J, Ikeda T, Kakeji Y, Minami Y

    Cancer science   110 ( 4 )   1306 - 1316   2019.4( ISSN:1347-9032

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1111/cas.13970

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  • Genetic interactions between Ror2 and Wnt9a, Ror1 and Wnt9a and Ror2 and Ror1: Phenotypic analysis of the limb skeleton and palate in compound mutants.

    Weissenböck M, Latham R, Nishita M, Wolff LI, Ho HH, Minami Y, Hartmann C

    Genes to cells : devoted to molecular & cellular mechanisms   24 ( 4 )   307 - 317   2019.4( ISSN:1356-9597

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    DOI : 10.1111/gtc.12676

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  • 【Wntシグナルと骨】非古典的Wntシグナルと細胞応答

    西田 満, 佐事 武, 南 康博

    Clinical Calcium   29 ( 3 )   291 - 297   2019.2( ISSN:0917-5857

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  • 【Wntシグナルと骨】非古典的Wntシグナルと細胞応答

    西田 満, 佐事 武, 南 康博

    Clinical Calcium   29 ( 3 )   291 - 297   2019.2( ISSN:0917-5857

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  • Synchronized mesenchymal cell polarization and differentiation shape the formation of the murine trachea and esophagus.

    Kishimoto K, Tamura M, Nishita M, Minami Y, Yamaoka A, Abe T, Shigeta M, Morimoto M

    Nature communications   9 ( 1 )   2816   2018.7

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    DOI : 10.1038/s41467-018-05189-2

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  • Critical role of the Ror-family of receptor tyrosine kinases in invasion and proliferation of malignant pleural mesothelioma cells.

    Saji T, Nishita M, Ogawa H, Doi T, Sakai Y, Maniwa Y, Minami Y

    Genes to cells : devoted to molecular & cellular mechanisms   23 ( 7 )   606 - 613   2018.7( ISSN:1356-9597

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    DOI : 10.1111/gtc.12599

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  • Expression of Ror2 Associated with Fibrosis of the Submandibular Gland.

    Takahashi D, Suzuki H, Kakei Y, Yamakoshi K, Minami Y, Komori T, Nishita M

    Cell structure and function   42 ( 2 )   159 - 167   2017.12( ISSN:0386-7196

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    DOI : 10.1247/csf.17019

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  • Protein kinase N3 promotes bone resorption by osteoclasts in response to Wnt5a-Ror2 signaling.

    Uehara S, Udagawa N, Mukai H, Ishihara A, Maeda K, Yamashita T, Murakami K, Nishita M, Nakamura T, Kato S, Minami Y, Takahashi N, Kobayashi Y

    Science signaling   10 ( 494 )   2017.8( ISSN:1945-0877

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    DOI : 10.1126/scisignal.aan0023

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  • Regulatory mechanisms and cellular functions of non-centrosomal microtubules.

    Nishita M, Satake T, Minami Y, Suzuki A

    Journal of biochemistry   162 ( 1 )   1 - 10   2017.7( ISSN:0021-924X

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    DOI : 10.1093/jb/mvx018

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  • Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness.

    Nishita M, Park SY, Nishio T, Kamizaki K, Wang Z, Tamada K, Takumi T, Hashimoto R, Otani H, Pazour GJ, Hsu VW, Minami Y

    Scientific reports   7 ( 1 )   1   2017.1

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    DOI : 10.1038/s41598-016-0028-x

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  • ROR1 is essential for proper innervation of auditory hair cells and hearing in humans and mice.

    Diaz-Horta O, Abad C, Sennaroglu L, Foster J 2nd, DeSmidt A, Bademci G, Tokgoz-Yilmaz S, Duman D, Cengiz FB, Grati M, Fitoz S, Liu XZ, Farooq A, Imtiaz F, Currall BB, Morton CC, Nishita M, Minami Y, Lu Z, Walz K, Tekin M

    Proceedings of the National Academy of Sciences of the United States of America   113 ( 21 )   5993 - 8   2016.5( ISSN:0027-8424

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    DOI : 10.1073/pnas.1522512113

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  • Essential role of Wnt5a-Ror1/Ror2 signaling in metanephric mesenchyme and ureteric bud formation.

    Qi X, Okinaka Y, Nishita M, Minami Y

    Genes to cells : devoted to molecular & cellular mechanisms   21 ( 4 )   325 - 34   2016.4( ISSN:1356-9597

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1111/gtc.12342

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  • Wnt5a-Ror2 signaling in mesenchymal stem cells promotes proliferation of gastric cancer cells by activating CXCL16-CXCR6 axis.

    Takiguchi G, Nishita M, Kurita K, Kakeji Y, Minami Y

    Cancer science   107 ( 3 )   290 - 7   2016.3( ISSN:1347-9032

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1111/cas.12871

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  • 【知る・見る・活かす!シグナリング研究2015 シグナル伝達の要素発見から時空間ダイナミクスへ】(第2章)シグナリングから見た生命現象 その破綻と疾患の理解 Wnt5a-Ror2シグナルによるがんの浸潤制御

    西田 満, 西尾 忠, 南 康博

    実験医学   33 ( 10 )   1612 - 1616   2015.6( ISSN:0288-5514

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  • Insight into the role of Wnt5a-induced signaling in normal and cancer cells.

    Endo M, Nishita M, Fujii M, Minami Y

    International review of cell and molecular biology   314   117 - 48   2015( ISSN:1937-6448

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    DOI : 10.1016/bs.ircmb.2014.10.003

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  • Insulin receptor substrate-4 binds to Slingshot-1 phosphatase and promotes cofilin dephosphorylation.

    Homma Y, Kanno S, Sasaki K, Nishita M, Yasui A, Asano T, Ohashi K, Mizuno K

    The Journal of biological chemistry   289 ( 38 )   26302 - 13   2014.9( ISSN:0021-9258

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    DOI : 10.1074/jbc.M114.565945

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  • Role of Wnt5a-Ror2 signaling in morphogenesis of the metanephric mesenchyme during ureteric budding.

    Nishita M, Qiao S, Miyamoto M, Okinaka Y, Yamada M, Hashimoto R, Iijima K, Otani H, Hartmann C, Nishinakamura R, Minami Y

    Molecular and cellular biology   34 ( 16 )   3096 - 105   2014.8( ISSN:0270-7306

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    DOI : 10.1128/MCB.00491-14

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  • 尿管芽形成におけるWnt5a-Ror2シグナルの役割

    西田 満, 喬 森, 宮本 真里, 沖中 由佳, 山田 真紀子, 飯島 一誠, 大谷 浩, Hartmann Christine, 西中村 隆一, 南 康博

    発達腎研究会誌   22 ( 1 )   11 - 14   2014.4( ISSN:0919-7532

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  • Critical role of Frizzled1 in age-related alterations of Wnt/β-catenin signal in myogenic cells during differentiation.

    Doi R, Endo M, Yamakoshi K, Yamanashi Y, Nishita M, Fukada S, Minami Y

    Genes to cells : devoted to molecular & cellular mechanisms   19 ( 4 )   287 - 96   2014.4( ISSN:1356-9597

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1111/gtc.12132

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  • Diabetic osteopenia by decreased β-catenin signaling is partly induced by epigenetic derepression of sFRP-4 gene.

    Mori K, Kitazawa R, Kondo T, Mori M, Hamada Y, Nishida M, Minami Y, Haraguchi R, Takahashi Y, Kitazawa S

    PloS one   9 ( 7 )   e102797   2014

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1371/journal.pone.0102797

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  • Activation of Wnt5a-Ror2 signaling associated with epithelial-to-mesenchymal transition of tubular epithelial cells during renal fibrosis.

    Li X, Yamagata K, Nishita M, Endo M, Arfian N, Rikitake Y, Emoto N, Hirata K, Tanaka Y, Minami Y

    Genes to cells : devoted to molecular & cellular mechanisms   18 ( 7 )   608 - 19   2013.7( ISSN:1356-9597

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1111/gtc.12064

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  • 【Wntシグナルと骨】非古典的Wntシグナルの情報伝達と細胞応答

    西田 満, 遠藤 光晴, 南 康博

    Clinical Calcium   23 ( 6 )   809 - 815   2013.5( ISSN:0917-5857

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

  • Ror family receptor tyrosine kinases regulate the maintenance of neural progenitor cells in the developing neocortex.

    Endo M, Doi R, Nishita M, Minami Y

    Journal of cell science   125 ( Pt 8 )   2017 - 29   2012.4( ISSN:0021-9533

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    DOI : 10.1242/jcs.097782

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  • Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis.

    Maeda K, Kobayashi Y, Udagawa N, Uehara S, Ishihara A, Mizoguchi T, Kikuchi Y, Takada I, Kato S, Kani S, Nishita M, Marumo K, Martin TJ, Minami Y, Takahashi N

    Nature medicine   18 ( 3 )   405 - 12   2012.2( ISSN:1078-8956

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    DOI : 10.1038/nm.2653

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  • Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase (MMP-13) expression.

    Yamagata K, Li X, Ikegaki S, Oneyama C, Okada M, Nishita M, Minami Y

    The Journal of biological chemistry   287 ( 2 )   1588 - 99   2012.1( ISSN:0021-9258

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    DOI : 10.1074/jbc.M111.315127

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  • Analysis of Wnt/planar cell polarity pathway in cultured cells.

    Endo M, Nishita M, Minami Y

    Methods in molecular biology (Clifton, N.J.)   839   201 - 14   2012( ISSN:1064-3745

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    DOI : 10.1007/978-1-61779-510-7_16

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  • Critical role of Wnt5a-Ror2 signaling in motility and invasiveness of carcinoma cells following Snail-mediated epithelial-mesenchymal transition.

    Ren D, Minami Y, Nishita M

    Genes to cells : devoted to molecular & cellular mechanisms   16 ( 3 )   304 - 15   2011.3( ISSN:1356-9597

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1111/j.1365-2443.2011.01487.x

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  • Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization.

    Nishita M, Itsukushima S, Nomachi A, Endo M, Wang Z, Inaba D, Qiao S, Takada S, Kikuchi A, Minami Y

    Molecular and cellular biology   30 ( 14 )   3610 - 9   2010.7( ISSN:0270-7306

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    DOI : 10.1128/MCB.00177-10

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  • Cell/tissue-tropic functions of Wnt5a signaling in normal and cancer cells.

    Nishita M, Enomoto M, Yamagata K, Minami Y

    Trends in cell biology   20 ( 6 )   346 - 54   2010.6( ISSN:0962-8924

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1016/j.tcb.2010.03.001

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  • Ror2 is required for midgut elongation during mouse development.

    Yamada M, Udagawa J, Matsumoto A, Hashimoto R, Hatta T, Nishita M, Minami Y, Otani H

    Developmental dynamics : an official publication of the American Association of Anatomists   239 ( 3 )   941 - 53   2010.3( ISSN:1058-8388

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1002/dvdy.22212

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  • Ror-family receptor tyrosine kinases in noncanonical Wnt signaling: their implications in developmental morphogenesis and human diseases.

    Minami Y, Oishi I, Endo M, Nishita M

    Developmental dynamics : an official publication of the American Association of Anatomists   239 ( 1 )   1 - 15   2010.1( ISSN:1058-8388

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1002/dvdy.21991

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  • Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling.

    Enomoto M, Hayakawa S, Itsukushima S, Ren DY, Matsuo M, Tamada K, Oneyama C, Okada M, Takumi T, Nishita M, Minami Y

    Oncogene   28 ( 36 )   3197 - 208   2009.9( ISSN:0950-9232

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1038/onc.2009.175

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  • Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development.

    He F, Xiong W, Yu X, Espinoza-Lewis R, Liu C, Gu S, Nishita M, Suzuki K, Yamada G, Minami Y, Chen Y

    Development (Cambridge, England)   135 ( 23 )   3871 - 9   2008.12( ISSN:0950-1991

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    DOI : 10.1242/dev.025767

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  • Receptor tyrosine kinase Ror2 mediates Wnt5a-induced polarized cell migration by activating c-Jun N-terminal kinase via actin-binding protein filamin A.

    Nomachi A, Nishita M, Inaba D, Enomoto M, Hamasaki M, Minami Y

    The Journal of biological chemistry   283 ( 41 )   27973 - 81   2008.10( ISSN:0021-9258

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    DOI : 10.1074/jbc.M802325200

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  • Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex.

    Yamamoto S, Nishimura O, Misaki K, Nishita M, Minami Y, Yonemura S, Tarui H, Sasaki H

    Developmental cell   15 ( 1 )   23 - 36   2008.7( ISSN:1534-5807

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1016/j.devcel.2008.05.007

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  • Ror2 modulates the canonical Wnt signaling in lung epithelial cells through cooperation with Fzd2.

    Li C, Chen H, Hu L, Xing Y, Sasaki T, Villosis MF, Li J, Nishita M, Minami Y, Minoo P

    BMC molecular biology   9   11   2008.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1186/1471-2199-9-11

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  • Wnt5a modulates glycogen synthase kinase 3 to induce phosphorylation of receptor tyrosine kinase Ror2.

    Yamamoto H, Yoo SK, Nishita M, Kikuchi A, Minami Y

    Genes to cells : devoted to molecular & cellular mechanisms   12 ( 11 )   1215 - 23   2007.11( ISSN:1356-9597

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1111/j.1365-2443.2007.01128.x

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  • Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration.

    Nishita M, Yoo SK, Nomachi A, Kani S, Sougawa N, Ohta Y, Takada S, Kikuchi A, Minami Y

    The Journal of cell biology   175 ( 4 )   555 - 62   2006.11( ISSN:0021-9525

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.1083/jcb.200607127

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  • [Role of cofilin phosphorylation in cell migration].

    Nishita M, Mizuno K

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   51 ( 6 Suppl )   516 - 21   2006.5( ISSN:0039-9450

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  • MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration.

    Kobayashi M, Nishita M, Mishima T, Ohashi K, Mizuno K

    The EMBO journal   25 ( 4 )   713 - 26   2006.2( ISSN:0261-4189

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    DOI : 10.1038/sj.emboj.7600973

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  • Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration.

    Nishita M, Tomizawa C, Yamamoto M, Horita Y, Ohashi K, Mizuno K

    The Journal of cell biology   171 ( 2 )   349 - 59   2005.10( ISSN:0021-9525

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    DOI : 10.1083/jcb.200504029

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  • The receptor tyrosine kinase Ror2 associates with and is activated by casein kinase Iepsilon.

    Kani S, Oishi I, Yamamoto H, Yoda A, Suzuki H, Nomachi A, Iozumi K, Nishita M, Kikuchi A, Takumi T, Minami Y

    The Journal of biological chemistry   279 ( 48 )   50102 - 9   2004.11( ISSN:0021-9258

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    DOI : 10.1074/jbc.M409039200

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  • Caspase-mediated cleavage and activation of LIM-kinase 1 and its role in apoptotic membrane blebbing.

    Tomiyoshi G, Horita Y, Nishita M, Ohashi K, Mizuno K

    Genes to cells : devoted to molecular & cellular mechanisms   9 ( 6 )   591 - 600   2004.6( ISSN:1356-9597

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    DOI : 10.1111/j.1356-9597.2004.00745.x

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  • A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia.

    Nagata-Ohashi K, Ohta Y, Goto K, Chiba S, Mori R, Nishita M, Ohashi K, Kousaka K, Iwamatsu A, Niwa R, Uemura T, Mizuno K

    The Journal of cell biology   165 ( 4 )   465 - 71   2004.5( ISSN:0021-9525

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    DOI : 10.1083/jcb.200401136

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  • Phosphoinositide 3-kinase-mediated activation of cofilin phosphatase Slingshot and its role for insulin-induced membrane protrusion.

    Nishita M, Wang Y, Tomizawa C, Suzuki A, Niwa R, Uemura T, Mizuno K

    The Journal of biological chemistry   279 ( 8 )   7193 - 8   2004.2( ISSN:0021-9258

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    DOI : 10.1074/jbc.M312591200

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  • Involvement of NLK and Sox11 in neural induction in Xenopus development.

    Hyodo-Miura J, Urushiyama S, Nagai S, Nishita M, Ueno N, Shibuya H

    Genes to cells : devoted to molecular & cellular mechanisms   7 ( 5 )   487 - 96   2002.5( ISSN:1356-9597

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    DOI : 10.1046/j.1365-2443.2002.00536.x

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  • Stromal cell-derived factor 1alpha activates LIM kinase 1 and induces cofilin phosphorylation for T-cell chemotaxis.

    Nishita M, Aizawa H, Mizuno K

    Molecular and cellular biology   22 ( 3 )   774 - 83   2002.2( ISSN:0270-7306

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    DOI : 10.1128/mcb.22.3.774-783.2002

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  • Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.

    Tago K, Nakamura T, Nishita M, Hyodo J, Nagai S, Murata Y, Adachi S, Ohwada S, Morishita Y, Shibuya H, Akiyama T

    Genes & development   14 ( 14 )   1741 - 9   2000.7( ISSN:0890-9369

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  • Interaction between Wnt and TGF-beta signalling pathways during formation of Spemann's organizer.

    Nishita M, Hashimoto MK, Ogata S, Laurent MN, Ueno N, Shibuya H, Cho KW

    Nature   403 ( 6771 )   781 - 5   2000.2( ISSN:0028-0836

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    DOI : 10.1038/35001602

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  • Smad8B, a Smad8 splice variant lacking the SSXS site that inhibits Smad8-mediated signalling.

    Nishita M, Ueno N, Shibuya H

    Genes to cells : devoted to molecular & cellular mechanisms   4 ( 10 )   583 - 91   1999.10( ISSN:1356-9597

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    DOI : 10.1046/j.1365-2443.1999.00285.x

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  • Involvement of the p38 mitogen-activated protein kinase pathway in transforming growth factor-beta-induced gene expression.

    Hanafusa H, Ninomiya-Tsuji J, Masuyama N, Nishita M, Fujisawa J, Shibuya H, Matsumoto K, Nishida E

    The Journal of biological chemistry   274 ( 38 )   27161 - 7   1999.9( ISSN:0021-9258

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    DOI : 10.1074/jbc.274.38.27161

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  • The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF.

    Ishitani T, Ninomiya-Tsuji J, Nagai S, Nishita M, Meneghini M, Barker N, Waterman M, Bowerman B, Clevers H, Shibuya H, Matsumoto K

    Nature   399 ( 6738 )   798 - 802   1999.6( ISSN:0028-0836

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    DOI : 10.1038/21674

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  • XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway.

    Yamaguchi K, Nagai S, Ninomiya-Tsuji J, Nishita M, Tamai K, Irie K, Ueno N, Nishida E, Shibuya H, Matsumoto K

    The EMBO journal   18 ( 1 )   179 - 87   1999.1( ISSN:0261-4189

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    DOI : 10.1093/emboj/18.1.179

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  • Nuclear translocation and increased expression of Bax and disturbance in cell cycle progression without prominent apoptosis induced by hyperthermia.

    Nishita M, Inoue S, Tsuda M, Tateda C, Miyashita T

    Experimental cell research   244 ( 1 )   357 - 66   1998.10( ISSN:0014-4827

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    DOI : 10.1006/excr.1998.4203

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  • BRAM1, a BMP receptor-associated molecule involved in BMP signalling.

    Kurozumi K, Nishita M, Yamaguchi K, Fujita T, Ueno N, Shibuya H

    Genes to cells : devoted to molecular & cellular mechanisms   3 ( 4 )   257 - 64   1998.4( ISSN:1356-9597

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  • Induction of lateral outgrowths on the chelae of the crayfish, Procambarus clarkii (Girard).

    Murayama, O., Nakatani, I., and Nishita, M.

    Crustacean Res.   23   69 - 73   1994

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI : 10.18353/crustacea.23.0_69

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Books

  • Lippincott's Illustrated Reviews

    2023.11 

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    Language:Japanese   Book type:Textbook, survey, introduction

  • Lippincott's Illustrated Reviews

    2019 

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    Language:Japanese   Book type:Textbook, survey, introduction

  • Lippincott's Illustrated Reviews

    2015 

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    Language:Japanese   Book type:Textbook, survey, introduction

  • Receptor Tyrosine Kinases: Family and Subfamilies

    Wheeler, D. L, Yarden, Y

    Humana Press (Springer)  2015 

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    Language:Japanese   Book type:Scholarly book

  • Lippincott's Illustrated Reviews

    2011 

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    Language:Japanese   Book type:Textbook, survey, introduction

  • Lippincott's Illustrated Reviews

    2008 

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    Language:Japanese   Book type:Textbook, survey, introduction

  • Lippincott's Illustrated Reviews

    2005 

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Presentations

  • Mesenchymal stromal cell-derived CXCL16 promotes proliferation and migration of gastric cancer cells by inducing STAT3-mediated expression of Ror1

    ASCB/EMBO meeting 2019  

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    Event date: 2019.12

  • Ror1 signaling through Dvl and Rif promotes invasion of lung adenocarcinoma cells

    ASCB/EMBO 2019 meeting  

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    Event date: 2019.12

  • 間葉系間質細胞由来のCXCL16は胃癌細胞においてSTAT3経路を介してRor1の発現を誘導し増殖と遊走を促進する

    第78回日本癌学会総会  

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    Event date: 2019.9

  • Wnt5a-Ror1シグナルはRifを介した糸状突起形成によって肺腺がん細胞の浸潤を促進する

    第78回日本癌学会学術総会  

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    Event date: 2019.9

  • Wnt5a-Ror signaling in cancer cell proliferation and invasion

    第19回日本蛋白質科学会年会・第71回日本細胞生物学会大会 合同年次大会  

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    Event date: 2019.6

  • Ror1 promotes invasion of lung adenocarcinoma cells through small GTPase Rif-mediated filopodia formation.

    ASCB/EMBO 2018 meeting  

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    Event date: 2018.12

  • IFT20は大腸がん細胞の集団的浸潤における先導細胞の極性を制御する

    第41回日本分子生物学会年会  

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    Event date: 2018.11

  • Ror1はSmgGDS-Rif経路を介して肺腺がん細胞の糸状突起形成と浸潤を促進する

    第77回日本癌学会学術総会  

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    Event date: 2018.9

  • Rif低分子量Gタンパク質による核膜タンパク質の動態制御と老化との関連

    AMED「老化メカニズムの解明・制御プロジェクト」第1回リトリート  

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    Event date: 2018.2

  • Novel role of Ror2 signaling in regulating Golgi structure and polarity for tumor cell invasion

    International Joint Symposium in Kobe 2017 University of Washington University of Oslo and Kobe University  

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    Event date: 2017.3

  • がん細胞浸潤におけるRor2受容体型チロシンキナーゼの新たな機能

    第39回日本分子生物学会年会  

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    Event date: 2016.12

  • IFT20はゴルジ体における微小管形成を促進することでRor2シグナル依存的ながん細胞浸潤を制御する

    第39回日本分子生物学会年会  

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    Event date: 2016.12

  • Ror2受容体型チロシンキナーゼのがんー胎児タンパク質としての機能

    第75回日本癌学会総会学術総会  

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    Event date: 2016.10

  • Wnt5a-Ror2シグナルは繊毛タンパク質IFT20の発現誘導を介してがん細胞の浸潤を制御する

    第38回日本分子生物学会年会  

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    Event date: 2015.12

  • Novel role for Wnt5a-Ror2 signaling in regulating polarity and structure of the Golgi apparatus in osteosarcoma cells.

    University of Washington-Kobe University Joint Symposium on Cell Signaling  

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    Event date: 2015.9

  • Wnt5a-Ror2 signaling induces expression of the ciliary protein IFT20 to regulate the integrity of the Golgi apparatus and reorientation of the centrosome during tumor cell invasion

    新学術領域研究「上皮管腔組織形成」 第2回国際シンポジウム  

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    Event date: 2015.8

  • Role of Wnt5a-Ror signaling in morphogenesis of the metanephric mesenchyme during ureteric budding

    新学術領域研究「上皮管腔組織形成」 第2回国際シンポジウム  

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    Event date: 2015.8

  • 繊毛タンパク質IFT20による骨肉腫細胞の浸潤制御

    第7回シグナルネットワーク研究会  

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    Event date: 2015.6

  • Role of Wnt5a-Ror2 signaling in tumor invasion

    University of Washington and Kobe University International Joint Symposium  

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    Event date: 2014.12

  • Role of Wnt5a-Ror2 signaling in patterning the metanephric mesenchyme during ureteric budding

    Keystone Symposia "Developmental Pathways and Cancer: Wnt, Notch and Hedgehog(J7)"  

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    Event date: 2014.2

  • 尿管芽形成におけるWnt5a-Ror2シグナルの役割と腎尿路奇形

    第22回発達腎研究会  

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    Event date: 2013.9

  • 炎症性サイトカインによりアストロサイトで発現誘導されるRor1受容体の機能解析

    2013年度包括脳ネットワーク夏のワークショップ  

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    Event date: 2013.8

  • Roles of Wnt/PCP signaling in pathological conditions of epithelial tubular tissues

    First International Meeting for Epithelial Tubulology  

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    Event date: 2013.6

  • マウス腎臓発生におけるWnt5a・Ror2シグナルの役割

    第35回日本分子生物学会年会  

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    Event date: 2012.12

  • The Role of Ror-Family Receptor Tyrosine Kinases in Maintaining Neocortical Neural Progenitor Cells

    1st International Symposium Neocortical Organization  

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    Event date: 2012.3

  • Ror-family receptor tyrosine kinases regulate maintenance of neural progenitor cells in the developing neocortex

    第63回日本細胞生物学会大会  

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    Event date: 2011.6

  • Wnt5a-Ror2シグナルによる細胞極性•移動制御とがんの浸潤

    第62回日本細胞生物学会大会  

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    Event date: 2010.5

  • Ror2受容体型チロシンキナーゼによる細胞極性・移動制御におけるタンパク質リン酸化の役割

    第82回日本生化学会大会  

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    Event date: 2009.10

  • Ror2受容体型チロシンキナーゼを介したWnt5aシグナル伝達制御

    第1回シグナルネットワーク研究会  

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    Event date: 2009.5

  • 受容体型チロシンキナーゼRor2はアクチン結合蛋白質filamin Aを介してWnt5aによるc-Jun N-terminalキナーゼの活性化と細胞極性・移動を制御する

    第31回日本分子生物学会第81回日本生化学会大会合同大会  

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    Event date: 2008.12

  • Wnt5a/Ror2シグナルによるDishevelledの動態制御

    第31回日本分子生物学会年会 第81回日本生化学会大会 合同大会  

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    Event date: 2008.12

  • Wnt5a/Ror2シグナルによる細胞運動制御

    第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会  

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    Event date: 2008.12

  • Wnt5a/Ror2経路はMMP-13を介して骨肉腫細胞のinvadopodia形成と浸潤を制御する

    第31回日本分子生物学会年会 第81回日本生化学会大会 合同大会  

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    Event date: 2008.12

  • Regulation of Dishevelled in Wnt5a/Ror2 signaling

    第2回日韓共同研究プログラム合同ミーティング  

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    Event date: 2008.11

  • Ror2 regulates cytoskeletal rearrangements to mediate Wnt5a-induced polarized cell migration

    第30回日本分子生物学会  

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    Event date: 2007.12

  • Ror2 receptor tyrosine kinase and its implication in human diseases

    日韓共同研究プログラム第1回二国間会議  

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    Event date: 2007.10

  • Role of Ror2 receptor tyrosine kinase in the regulation of Wnt5a-induced cell polarization and migration

    日韓共同研究プログラム第1回二国間会議  

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    Event date: 2007.10

  • Roles of receptor tyrosine kinase Ror2 in Wnt5a-induced non-canonical Wnt signaling

    WNT2007INLAJOLLA  

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    Event date: 2007.6

  • Wnt5aによる細胞移動におけるRor2の機能解析

    日本分子生物学会2006フォーラム  

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    Event date: 2006.12

  • Roles for Ror2 receptor tyrosine kinase in the regulation of Wnt5a signaling and cell migration

    2006 international symposium of kobe university 21st century COE program on signsl transduction in memory of Prof. Yasutomi Nkaishizu  

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    Event date: 2006.8

  • Regulation of Wnt5a-induced cell migration by Ror2 receptor tyrosine kinase

    20th IUBMB Congress  

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    Event date: 2006.6

  • Roles for Ror2 receptor tyrosine kinase in the regulation of Wnt5a signaling and cell migration

    2006 international symposium of kobe university 21st century COE program on signsl transduction in memory of Prof. Yasutomi Nishizuka  

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    Event date: 2006.2

  • 受容体型チロシンキナーゼRor2によるWnt/PCP経路の制御とその細胞運動における役割

    第28回日本分子生物学会  

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    Event date: 2005.12

  • Ror2-mediated cytoskeletal reorganization by differential regulation of Dishevelled proteins

    第58回日本細胞生物学会大会  

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    Event date: 2005.6

  • 受容体型チロシンキナーゼRor2の細胞外・細胞内ドメイン依存的機能によるWntシグナルおよび細胞骨格系の制御

    第52回日本生化学会近畿支部例会  

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    Event date: 2005.5

  • PI3-kinase-Mediated Activation of Cofilin Phosphatase Slingshot-1L Controls Insulin-induced Membrane Protrusion

    the 43rd American Society for Cell Biology Annual Meeting  

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    Event date: 2003.12

  • Phosphorylation and activation of LIM-kinase 1 by p38 MAP-kinase in vascular endothelial growth factor-induced actin reorganization

    The Gordon Research Conference on Mechanisms of Cell Signalling  

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    Event date: 2003.6

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Research Projects

  • Wntシグナルに基づく新たな直腸癌化学放射線免疫複合療法の試み

    Grant number:21K08798  2021.4 - 2024.3

    基盤研究(C)

    古出 隆大, 西田 満, 松田 武, 掛地 吉弘, 山下 公大

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    今年度は、ヒト直腸癌術前化学放射線療法(NACRT)におけるWntシグナル活性と腫瘍浸潤リンパ球(TIL)の免疫組織解析を行った。当初は、深層学習アルゴリズムを用いて解析予定であったが、アルゴリズムの学習・構築に想定以上の症例数と時間を要したため、通常通り手作業でβ-カテニン等の発現解析を行った。また、各症例の予後との関連性も比較検討した。
    NACRT直腸癌生検組織における免疫組織学的解析において、β-カテニン発現強度とNACRT奏効度は有意に相関しており、β-カテニン強発現群において、NACRT奏効度は低かった。また、腫瘍学的成績においても、全生存率はβ-カテニン高発現群はその他と比較して有意に予後不良であった。一方、無再発生存率は、各群間で有意差はなかったが、β-カテニン発現最弱群は、他の3群よりも良好な傾向があった。また、腫瘍浸潤リンパ球について解析したところ、NACRT後直腸癌において、CD8+浸潤の程度と組織学的奏効度は高い相関性を示した。また、CD8+の高浸潤群は、低浸潤群と比較して、有意に無再発生存率が良好であった。一方、レジデントメモリーCD8+T細胞の細胞密度は、無再発生存率に寄与しなかった。

  • 集団的癌細胞浸潤におけるRif低分子量Gタンパク質の機能解明

    2021.4 - 2022.3

  • ゴルジ体微小管の構築制御に基づく癌細胞の集団的浸潤機構の解明

    2020.4 - 2023.3

  • ゴルジ体微小管の構築制御に基づく癌細胞の集団的浸潤機構の解明

    Grant number:20K07575  2020.4 - 2023.3

    基盤研究(C)

    西田 満

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    大腸癌細胞株DLD細胞を用いて集団的浸潤過程での、リーダー細胞とフォロワー細胞におけるゴルジ体由来および 中心体由来微小管の動態について検討することとした。まず、安定化微小管のマーカーであるアセチル化チューブリンの免疫蛍光染色を行った結果、癌細胞集団の中でも、特にリーダー細胞において浸潤方向へ極性化したアセチル化チューブリンの強い染色が観察され、微小管が安定化し蓄積していることが確認された。そこで、リーダー細胞での微小管安定化におけるIFT20の役割について検討するため、IFT20をsiRNAを用いてノックダウンしたDLD1細胞を用いて同様の解析を行った。その結果、IFT20をノックダウンしたリーダー細胞においては、アセチル化チューブリンで染色される微小管が浸潤方向とは関係ない方向に伸びたり、曲がったりしていることが観察された。同様の結果は、別の大腸癌細胞株HCT116細胞においても認められた。したがって、リーダー細胞においてIFT20は極性化した安定化微小管のネットワーク形成に必須な役割を担っていることが示された。一方、これらの実験において観察されたアセチル化チューブリンのほとんどは、中心体に接していなかったことから、ゴルジ体由来微小管である可能性が考えられた。実際、アセチル化チューブリンとゴルジ体の二重染色を行った結果、ほとんどの、アセチル化チューブリンはゴルジ体と接していることが観察された。さらに、IFT20 をノックダウンすることによりゴルジ体周囲のアセチル化チューブリンの蛍光強度が優位に低下した。したがって、IFT20はリーダー細胞においてゴルジ体由来微小管の安定化と極性化に寄与することが示された。

  • 集団的がん細胞浸潤を司るリーダー細胞の特性解明

    2020.4 - 2021.3

  • がん細胞浸潤におけるゴルジ体内タンパク質輸送の分子機構

    2018.4 - 2020.3

    西田 満

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    Authorship:Principal investigator 

  • Functional analysis of Ror1-Rif signaling in malignant progression of non-small cell lung cancer cells

    Grant number:17K08634  2017.4 - 2020.3

    Grant-in-Aid for Scientific Research (C)

    Nishita Michiru

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    Authorship:Principal investigator  Grant type:Competitive

    We studied the role of Ror1 in invasive properties of non-small cell lung cancer (NSCLC) cells. We have shown that, in PC-9 NSCLC cells, Ror1 induces formation of polarized filopodia through the Rho-family small GTPase, Rif, in 3D-Matrigel. These filopodia were spacially associated with degradation of Matrigel. Suppressed expression of Ror1 or Rif inhibited both filopodia formation and Matrigel degradation. We have also shown that PC-9 cells express high levels of Wnt5a, leading to constitutively activated Wnt5a-Ror1-Dvl signaling, which is required for their invasiveness. Furthermore, SmgGDS was identified as a Rif-binding partner that promotes Rif-induced filopodia formation and invasion in PC-9 cells. Taken together, these results suggest that Wnt5a-Ror1 signaling mediated by SmgGDS and Rif regulates filopodia formation to promote invasion of NSCLC cells.

  • Analysis of molecular mechanisms of Wnt5a-Ror signaling in repair after tissue damage, inflammation, and cancer progression

    Grant number:16H05152  2016.4 - 2019.3

    Grant-in-Aid for Scientific Research (B)

    Minami Yasuhiro

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    Grant type:Competitive

    It has been well established that Ror1 and Ror2 receptor tyrosine kinases play important roles in developmental morphogenesis and tissue-/organo-genesis by acting as receptors for Wnt5a. In this study, we have shown that Ror1 and Ror2 play important roles in regulating repair and inflammatory responses after damage of brain neocortex and skeletal muscle by using experimental animal models. Furthermore, we show that Ror2 as well as Ror1 are expressed at high levels in various types of cancer cells, including osteosarcoma cells, breast cancer cells, malignant pleural mesotheliomas, and colo-rectal cancer cells, thereby promoting invasion of these cancer cells by activating similar and/or different signaling pathways.

  • Wnt5a/Ror2シグナルと一次繊毛の機能連関による腎上皮細胞の極性制御

    2015.4 - 2017.3

  • Rifによるエメリンの分解制御とその核膜動態における役割

    2013.4 - 2016.3

  • 後腎間葉の細胞移動による尿管芽誘導機構

    2013.4 - 2015.3

  • 上皮間葉転換を伴う炎症や癌の進展におけるWnt5a-Rorシグナルの分子病態解析

    2012.4 - 2015.3

  • A-STEP「肺および腎線維化の病態解明と阻害薬開発のための新規マウスモデルの開発」

    2011

  • Ror1-mediated signaling and its role in development and cancer

    Grant number:22790291  2010

    Grant-in-Aid for Young Scientists (B)

    NISHITA Michiru

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    Authorship:Principal investigator  Grant type:Competitive

    Mouse embryonic fibroblasts isolated from Ror1 ; Ror2 double knockout mice and human Burkitt's lymphoma cells were used to study their responses to Wnt5a. We found that inhibition of Wnt/.-catenin signaling by Wnt5a is mediated not only by Ror2 but also by Ror1. We also found that Ror1 is overexpressed in human triple-negative breast cancer cells and thereby activates signaling molecules, such as c-Src, Akt, Erk and Stat3, and cell proliferation.

  • Functional analyses of receptor tyrosine kinases, Ror1 and Ror2, in Wnt signalin

    Grant number:21390080  2009 - 2011

    Grant-in-Aid for Scientific Research (B)

    MINAMI Yasuhiro, NISHITA Michiru, ENDO Mitsuharu

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    Grant type:Competitive

    In mammals, including humans, binding of an secreted protein, Wnt5a, to its cognate receptors, the receptor tyrosine kinases, Ror1 and Ror2, elicits intracellular signalings that play important roles in the morphogenesis of tissues and organs during the developmental processes. In this study, we have shown that Wnt5a-Ror1/Wnt5a-Ror2 signalings play important roles in the morphogenesis of tissues and organs by regulating cell polarity and migration, and have elucidated the relationship between abnormalities in these signalings and developmental anomalies and cancer invasion.

  • Analysis of regulatory mechanisms for cell migration and cell polarity by Wnt5a and Ror2 receptor tyrosine kinase

    Grant number:19390076  2007 - 2008

    Grant-in-Aid for Scientific Research (B)

    MINAMI Yasuhiro

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    Grant type:Competitive

  • Roles of Wnt5a-Ror2 in actin dynamics and cell migration

    Grant number:19790233  2007

    Grant-in-Aid for Young Scientists (B)

    NISHITA Michiru

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    Authorship:Principal investigator  Grant type:Competitive

  • Molecular mechanism of DNA damage-induced responses and its failure by carcinogenesis

    Grant number:17014062  2005 - 2009

    Grant-in-Aid for Scientific Research on Priority Areas

    MINAMI Yasuhiro, YODA AKINORI, NISHITA MICHIRU, ENDO MITSUHARU, YAMAGATA KAORU

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    Grant type:Competitive

    It has been shown that following DNA damage anti-oncogenic protein kinases, including ATM, Chk1 and Chk2 kinases, are phosphorylated and activated, thereby executing checkpoint machinery, leading to cell-cycle arrest. Subsequently, oncogenic Wip1 phosphatase are induced by p53, and dephosphorylates and inactivates phosphorylated -protein kinases, thereby re-starts arrested cell-cycle. In addition, we have shown that in osteosarcoma cell lines constitutively active Wnt5a/Ror2 signaling induces matrix metalloproteinase-13, thereby confers invasive properties on osteosarcoma cells.

  • Ror2受容体型チロシンキナーゼによる細胞運動の制御機構

    Grant number:17790211  2005

    若手研究(B)

    西田 満

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    Authorship:Principal investigator  Grant type:Competitive

    Wnt5aシグナル伝達系におけるRor2の役割を調べるため、Ror2を発現していないL細胞とRor2を発現しているNIH3T3細胞を用い、それらのWnt5aに対する応答性を比較した。Wntシグナルの活性化は細胞内シグナル伝達因子Dvlのリン酸化を誘導するため、Wnt5aに対する応答性はDvlのリン酸化を検出することによって評価した。解析の結果、NIH3T3細胞ではWnt5a刺激によってDvlがリン酸化されるのに対し、L細胞ではRor2の強制発現依存的にDvlがリン酸化された。したがって、Ror2の発現がWnt5aによるDvlのリン酸化に重要な役割を果たしていることが示唆された。次にRor2遺伝子欠損マウス胚(Ror2-/-)および野生型マウス胚(Ror2+/+)より単離した胚性線維芽細胞(MEF)を用いてWnt5a刺激によるDvlのリン酸化動態の解析を行った。その結果、Ror2+/+MEFにおいてはWnt5a刺激依存的にDvlのリン酸化が認められたのに対し、Ror2-/-MEFにおいてはそのリン酸化は認められなかった。したがってRor2はWnt5aによるDvlのリン酸化に必要であることが明らかになった。Dvlのリン酸化はWnt5aのほか、異なるタイプのWntであるWnt3aなどによっても引き起こされることが知られている。そこでWnt3aを用いて同様の解析を行った結果、Ror2+/+MEFとRor2-/-MEFにおいてWnt3a刺激によるDvlのリン酸化が同様に検出された。したがって、Ror2はWnt3aによるDvlのリン酸化には必要ではないことが明らかとなった。本研究からRor2はWnt5a特異的なDvlリン酸化制御を担っていることが明らかになった。

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