Effect of HGF on c-MET inhibition in gastric cancer
위암 세포에서 HGF 발현이 c-MET 억제에 미치는 영향에 관한 연구

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의과대학 협동과정 종양생물학전공
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서울대학교 대학원
Hepatocyte growth factorc-METtyrosine kinase inhibitorStomach neoplasms
학위논문 (석사)-- 서울대학교 대학원 : 종양생물학전공, 2017. 2. 김우호.
Aberrant expression and activation of hepatocyte growth factor (HGF) and its receptor c-MET have been implicated in tumorigenesis via promotion of tumor proliferation and metastasis. Increased expression of HGF and c-MET is associated with poor prognosis in various cancers. Recently, it has been reported that the expression of HGF induces resistance to tyrosine kinase inhibitors (TKIs) targeting EGFR, HER2, and BRAF. A key process mediating this resistance is activation of c-MET by HGF that results in trans-phosphorylation of other receptor tyrosine kinases (RTKs) or cross-talk between c-MET and other receptors. Here, we investigated the effects of HGF overexpression in the absence or presence of c-MET TKIs in gastric cancer cells. The effects of c-MET TKIs in gastric cancer cells with or without c-MET overexpression were also determined. Cells showing c-MET overexpression were responsive to c-MET TKIs while c-MET negative cells were not. Compared to the control, cells with induced HGF expression showed increase in anchorage-independent colony formation (P < 0.001). The c-MET TKIs inhibited HGF/c-MET downstream signaling, cell proliferation, migration, and invasion, and triggered cell cycle arrest. However, HGF induced cells were less affected. In the presence of c-MET TKIs, c-MET activation was dependent on HGF, and HGF expression reduced sensitivity to c-MET TKIs. In summary, c-MET TKIs had inhibitory effects only in cells overexpressing c-MET. Furthermore, overexpression of HGF resulted in resistance to c-MET TKIs, through an autocrine manner in gastric cancer cells.
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College of Medicine/School of Medicine (의과대학/대학원)Program in Cancer Biology (협동과정-종양생물학전공)Theses (Master's Degree_협동과정-종양생물학전공)
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