Systems analysis of molecular mechanisms of growth factor regulation of stem cells

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390062
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kanazawa University (2013); The University of Tokyo (2011-2012)
• Principal Investigator: GOTOH Noriko 金沢大学, がん進展制御研究所, 教授 (10251448)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 細胞・組織 / シグナル伝達 / マイクロアレイ / 発生・分化 / システム生物学

Research Abstract

In order to examine the molecular mechanisms how growth factor signaling play roles for maintenance of tissue specific stem cells and cancer stem cells, we made mutant mice of FRS2alpha or FRS2beta, mediators for intracellular signaling through FGF or EGF, respectively. We found that FRS2alpha plays important roles for axon path finding of optic nerves, development of inner ears and sensory neurons. On the other hand, FRS2beta plays important roles for maintenance of breast cancer stem cells.

Research Products

• [Journal Article] Fgfr1-Frs2/3 Signalling Maintains Sensory Progenitors during Inner Ear Hair Cell Formation (2014)
  • Author(s): Ono, K., Kita, T., Sato, S., O'Neill, P., Mak, S.-S., Paschaki, M., Ito, M., Gotoh, N., Kawakami, K. & Ladher, R.K.
  • Journal Title: PLOS Genetics Volume: 10 Pages: e1004118
  • Peer Reviewed
• [Journal Article] Frs2alpha and Shp2 signal independently of Gab to mediate FGF signaling in lens development (2014)
  • Author(s): Li, H., Tao, C., Cai, Z., Hertzler-Schaefer, K., Collins, T.N., Wang, F., Feng, G.-S., Gotoh, N. & Zhang, X.
  • Journal Title: J. Cell Sci Volume: 127 Pages: 571-582
  • Peer Reviewed
• [Journal Article] Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma (2013)
  • Author(s): Cai, Z., Tao, C., Li, H., Ladher, R., Gotoh, N., Feng, G.-S., Wang, F. & Zhang, X.
  • Journal Title: Development Volume: 140 Pages: 2711-2723
  • Peer Reviewed
• [Journal Article] An adaptor protein complex of FRS2beta and CIN85/CD2AP provides a novel mechanism for ErbB2/HER2 protein downregulation (2013)
  • Author(s): Minegishi, Y., Shibagaki, Y., Mizutani, A., Fujita, F., Tezuka, T., Kinoshita, M., Kuroda, M., Hattor, S. & Gotoh, N.
  • Journal Title: Cancer Sci Volume: 104 Pages: 345-352
  • Peer Reviewed
• [Journal Article] Epidermal growth factor receptor tyrosine kinase defines critical prognostic genes of stage I lung adenocarcinoma (2012)
  • Author(s): Yamauchi, M., Yamaguchi, R., Nakata, A., Kohno, T., Nagasaki, M., Shimamura, T., Imoto S., Saito A., Ueno, K., Hatanaka, Y., Yoshida, R., Higuchi, T., Nomura, M., Beer, D.G., Yokota, J., Miyano, S. & Gotoh, N.
  • Journal Title: PLoS ONE Volume: 7 Pages: e43923
  • Peer Reviewed
• [Journal Article] ErbB/NF-kB signaling controls mammosphere formation in human breast cancer (2012)
  • Author(s): Hinorara, K., Kobayashi S., Kanauchi, H., Shimizu, S., Nishioka, K., Tsuji, E., Tada, K., Umezawa, K., Mori, M., Ogawa, T., Inoue, J., Tojo, A. & Gotoh, N.
  • Journal Title: Proc. Natl. Acad. Sci., USA Volume: 109 Pages: 6584-6589
  • Peer Reviewed
• [Journal Article] Possible signaling pathways in cancer stem cells in breast cancer (2011)
  • Author(s): Gotoh, N
  • Journal Title: In : Cancer Stem Cells Theories and Practice , Chapter 13, Nikolic, A. (Ed.), INTECH, NY, USA
  • Peer Reviewed
• [Presentation] 殖因子制御遺伝子による予後予測診断と癌幹細胞の分子標的Prognostic gene signature and novel molecular targets derived from growth factor signaling (2013)
  • Author(s): 後藤典子
  • Organizer: JCA-JSMO 合同シンポジウム,第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-03
• [Presentation] 増殖因子制御遺伝子による肺癌の予後予測診断と乳癌幹細胞の分子標的がん・ゲノム・脳 支援活動 (2013)
  • Author(s): 後藤典子
  • Organizer: 合同シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2013-08-06
• [Presentation] Receptor tyrosine kinase signaling controls breast cancer stem cells and their niche (2012)
  • Author(s): 後藤典子
  • Organizer: 第35回日本分子生物学会年会ワークショップ「がん研究の新局面~Aktシグナルと癌幹細胞」オーガナイザー「早期肺がん予後予測シグネチャーとgefitinib 耐性の分子機構」
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-12
• [Presentation] 「増殖因子受容体による癌幹細胞とニッチ制御の分子機構」"Growth factor receptor signaling controls breast cancer stem cells and their niche" (2012)
  • Author(s): 後藤典子
  • Organizer: 第71回日本癌学会総会 シンポジウム「がん幹細胞の分子標的」
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] "ErbB/EGF receptor signaling is a key pathway for self-renewing breast cancer stem cells" "Cancer and stem cells" (2011)
  • Author(s): 後藤典子
  • Organizer: 第34回日本分子生物学会年会シンポジウム オーガナイザー
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Book] がん幹細胞におけるシグナルと可塑性のシステム的解析 実験医学 (2013)
  • Author(s): 後藤典子
  • Total Pages: 2919
• [Book] 増殖因子による乳がん幹細胞制御の分子機構 (2013)
  • Author(s): 後藤典子
  • Total Pages: 33-39
  • Publisher: Cytometory Research
• [Book] 神経幹細胞における増殖因子によるERK キナーゼの制御機構 (2013)
  • Author(s): 後藤典子
  • Total Pages: 661
  • Publisher: Clinical Neuroscience
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/system-seimei/index.htm
• [Patent(Industrial Property Rights)] CXCL1 の発現量に基づく肺癌患者の予後判定方法およびキット (2013)
  • Inventor(s): 後藤典子
  • Industrial Property Rights Holder: コニカミノルタ株式会社
  • Industrial Property Rights Type: 特願
  • Industrial Property Number: 2013-207513
  • Filing Date: 2013-10-02