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

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000); Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2011: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• 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 / 癌

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
  • 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] Frs2alpha and Shp2 signal independently of Gab to mediate FGF signaling in lens development (2013)
  • Author(s): 後藤 典子
  • Journal Title: J. Cell Sci. Volume: 127 Pages: 571-582
  • Peer Reviewed
• [Journal Article] Effect of in vivo administration of reprogramming factors in the mouse liver (2013)
  • Author(s): 後藤 典子
  • Journal Title: Oncol. Lett. Volume: 6 Pages: 323-328
• [Journal Article] Protooncogene TCL1b functions as an Akt kinase co-activator which exhibits oncogenic potency in vivo (2013)
  • Author(s): 後藤 典子
  • Journal Title: Oncogenesis Volume: 2 Issue: 9 Pages: 1-27
  • DOI: 10.1038/oncsis.2013.30
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma. (2013)
  • Author(s): 後藤 典子
  • Journal Title: Development Volume: 140 Pages: 2711-2723
  • Peer Reviewed
• [Journal Article] The acquisition of malignant potential in colon cancer is regulated by the stabilization of Atonal homolog 1 protein. (2013)
  • Author(s): 後藤 典子
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 432 Pages: 175-181
• [Journal Article] The acquisition of malignant potential in colon cancer is regulated by the stabilization of Atonal homolog 1 protein. (2013)
  • Author(s): Kano Y
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 432 Issue: 1 Pages: 175-181
  • DOI: 10.1016/j.bbrc.2013.01.034
  • Peer Reviewed / Open Access
• [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
  • 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] Identification of genes up-regulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinoma. (2012)
  • Author(s): 後藤 典子
  • Journal Title: Cancer Res Volume: 72 Issue: 1 Pages: 100-111
  • DOI: 10.1158/0008-5472.can-11-1403
  • Peer Reviewed
• [Journal Article] Identifying regulational alterations in gene regulatory networks by state space representation of vector autoregressive models and variational annealing (2012)
  • Author(s): 後藤 典子
  • Journal Title: BMC Genomics Volume: Suppl. 1, Issue: S1
  • DOI: 10.1186/1471-2164-13-s1-s6
  • Peer Reviewed
• [Journal Article] ErbB/NF-kB signaling controls mammosphere formation in human breast cancer (2012)
  • Author(s): Hinohara, K.
  • Journal Title: Proc.Natl.Acad.Sci Volume: (in press) Issue: 17 Pages: 6584-6589
  • DOI: 10.1073/pnas.1113271109
  • Peer Reviewed
• [Journal Article] Recent understanding of the molecular mechanisms for the efficacy and resistance of EGF receptor-specific tyrosine kinase inhibitors in non-small cell lung cancer. (2012)
  • Author(s): 後藤 典子
  • Journal Title: Expert Opin. Ther. Targets Volume: 16 Issue: 8 Pages: 771-781
  • DOI: 10.1517/14728222.2012.697155
  • Peer Reviewed
• [Journal Article] Epidermal growth factor receptor tyrosine kinase defines critical prognostic genes of stage I lung adenocarcinoma (2012)
  • Author(s): 後藤 典子
  • Journal Title: PLoS ONE Volume: 7 Issue: 9 Pages: e43923-e43923
  • DOI: 10.1371/journal.pone.0043923
  • Peer Reviewed
• [Journal Article] Systemically injected exosomes targeted to EGFR deliver anti-tumor microRNA to breast cancer cells (2012)
  • Author(s): 後藤 典子
  • Journal Title: Molecular Therapy Volume: 21 Issue: 1 Pages: 185-191
  • DOI: 10.1038/mt.2012.180
  • Peer Reviewed
• [Journal Article] NF-ｋB pathways in breast cancer stem cells for tumorigenesis (2012)
  • Author(s): 後藤 典子
  • Journal Title: Breast cancer, Bentham eBooks, Bentham Science Volume: 巻なし
  • 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
• [Journal Article] Preferential expression of potential markers for cancer stem cells in large cell neuroendocrine carcinoma of the lung (2011)
  • Author(s): 後藤 典子
  • Journal Title: Journal of Clinical Bioinformatics Volume: 1 Issue: 1 Pages: 23-23
  • DOI: 10.1186/2043-9113-1-23
  • Peer Reviewed
• [Journal Article] N-cadherin expression is a potential survival mechanism of gefitinib-resistant lung cancer cells (2011)
  • Author(s): 後藤 典子
  • Journal Title: Am. J. Cancer. Res Volume: 1 Pages: 823-833
  • Peer Reviewed
• [Journal Article] Somatic mutations of the EGF receptor and their signal transducers affect the efficacy of EGF receptor-specific tyrosine kinase inhibitors (2011)
  • Author(s): 後藤 典子
  • Journal Title: Int. J. Clin. Exp. Pathol Volume: 4 Pages: 403-409
  • Peer Reviewed
• [Journal Article] A genetic study of the effects of reduced Frs2alpha gene dosage in exostoses development and cartilage abnormalities observed in Ext2 heterozygous mutant mice (2011)
  • Author(s): 後藤 典子
  • Journal Title: Journal of Osaka Medical Center & Research Institute for Maternal & Child Health Volume: 26 Pages: 101-108
  • Peer Reviewed
• [Journal Article] FRS2 (2011)
  • Author(s): 後藤 典子
  • Journal Title: Encyclopedia of Signaling Molecules. Springer, Heidelberg, Germany Volume: 巻なし
  • 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] 増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 (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
  • Invited
• [Presentation] Receptor tyrosine kinase signaling controls breast cancer stem cells (2013)
  • Author(s): 後藤 典子
  • Organizer: SNUCRI & KUCRI Symposium
  • Place of Presentation: ソウル 韓国
  • Invited
• [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] 増殖因子による乳がん幹細胞制御の分子機構 (2012)
  • Author(s): 後藤 典子
  • Organizer: 第２２回日本サイトメトリー学会 シンポジウム
  • Place of Presentation: 千里ライフサイエンスセンター（大阪府豊中市）
  • Invited
• [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 (2012)
  • Author(s): 後藤 典子
  • Organizer: 第７１回日本癌学会総会 シンポジウム
  • Place of Presentation: ホテルロイトン札幌
  • Invited
• [Presentation] 乳癌幹細胞スフェア培養が解き明かす腫瘍形成の分子機構 (2012)
  • Author(s): 後藤 典子
  • Organizer: 第71回日本癌学会総会 ランチョンセミナー
  • Place of Presentation: ホテルロイトン札幌
  • Invited
• [Presentation] 早期肺がん予後予測シグネチャーとgefitinib耐性の分子機構 (2012)
  • Author(s): 後藤 典子
  • Organizer: 第３５回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
  • Invited
• [Presentation] 増殖因子による乳がん幹細胞制御の分子機構 (2012)
  • Author(s): 後藤 典子
  • Organizer: 第２２回日本サイトメトリー学会 シンポジウム
  • Place of Presentation: 千里ライフサイエンスセンター
  • Invited
• [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
• [Presentation] 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
  • Place of Presentation: パシフィコ横浜
  • Invited
• [Presentation] Growth factor signaling regulates breast cancer stem cells
  • Author(s): 後藤 典子
  • Organizer: Seminar series in School of Medicine, Yale University
  • Place of Presentation: New Haven, CT, USA
  • Invited
• [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
  • Author(s): 後藤 典子
  • Organizer: がん・ゲノム・脳 支援活動 合同シンポジウム
  • Place of Presentation: 東京
  • Invited
• [Presentation] 増殖因子による乳がん幹細胞制御の分子機構
  • Author(s): 後藤 典子
  • Organizer: Breast Cancer Conference
  • Place of Presentation: 東京
  • Invited
• [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
  • 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: 特許
  • Filing Date: 2013-10-02
• [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: 特許
  • Industrial Property Number: 2013-207513
  • Filing Date: 2013-10-02