https://scholars.lib.ntu.edu.tw/handle/123456789/465983
標題: | EGF-induced Grb7 recruits and promotes ras activity essential for the tumorigenicity of Sk-Br3 breast cancer cells | 作者: | Chu P.-Y. TSAI-KUN LI Ding S.-T. I-RUE LAI Shen T.-L. |
公開日期: | 2010 | 出版社: | American Society for Biochemistry and Molecular Biology Inc. | 卷: | 285 | 期: | 38 | 起(迄)頁: | 29279-29285 | 來源出版物: | Journal of Biological Chemistry | 摘要: | Co-amplification and co-overexpression of ErbB2 and Grb7 are frequently found in various cancers, including breast cancer. Biochemical and functional correlations of the two molecules have identified Grb7 to be a pivotal mediator downstream of ErbB2-mediated oncogenesis. However, it remains largely unknown how Grb7 is involve in the ErbB2-mediated tumorigenesis. In this study, we show that Grb7-mediated cell proliferation and growth are essential for the tumorigenesis that occurs in ErbB2-Grb7-overexpressing breast cancer cells. Intrinsically, EGF-induced de novo Grb7 tyrosine phosphorylation/activation recruits and activates Ras-GTPases and subsequently promotes the phosphorylation of ERK1/2, thereby stimulating tumor growth. Furthermore, we also found the anti-tumor effect could be synergized by co-treatment with Herceptin plus Grb7 knockdown in Sk-Br3 breast cancer cells. Our findings illustrate an underlying mechanism by which Grb7 promotes tumorigenesis through the formation of a novel EGFR-Grb7-Ras signaling complex, thereby highlighting the potential strategy of targeting Grb7 as an anti-breast cancer therapy. ? 2010 by The American Society for Biochemistry and Molecular Biology, Inc. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-77956556826&doi=10.1074%2fjbc.C110.114124&partnerID=40&md5=7b3942f0eb9f3da6b5c7d801fd341b94 https://scholars.lib.ntu.edu.tw/handle/123456789/465983 |
ISSN: | 0021-9258 | DOI: | 10.1074/jbc.C110.114124 | SDG/關鍵字: | Amino acids; Cell proliferation; Phosphatases; Phosphorylation; Antitumor effect; Breast Cancer; Breast cancer cells; Functional correlation; GTPases; Herceptin; Oncogenesis; Over-expression; Signaling complex; Tumor growth; Tumorigenesis; Tumorigenicity; Underlying mechanism; Tumors; epidermal growth factor; epidermal growth factor receptor 2; growth factor receptor bound protein 7; guanosine triphosphatase; mitogen activated protein kinase 1; Ras protein; trastuzumab; tyrosine; epidermal growth factor; epidermal growth factor receptor; growth factor receptor bound protein 7; monoclonal antibody; Ras protein; trastuzumab; animal cell; antineoplastic activity; article; breast cancer; breast carcinogenesis; cancer cell culture; cell growth; cell proliferation; controlled study; drug protein binding; drug targeting; enzyme activation; human; human cell; molecular mechanics; mouse; nonhuman; priority journal; protein function; protein phosphorylation; signal transduction; 3T3 cell line; animal; Breast Neoplasms; drug effects; female; genetics; immunoprecipitation; metabolism; phosphorylation; SCID mouse; tumor cell line; Western blotting; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Blotting, Western; Breast Neoplasms; Cell Line, Tumor; Epidermal Growth Factor; Female; GRB7 Adaptor Protein; Humans; Immunoprecipitation; Mice; Mice, SCID; NIH 3T3 Cells; Phosphorylation; ras Proteins; Receptor, Epidermal Growth Factor; Signal Transduction |
顯示於: | 解剖學暨細胞生物學科所 |
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