So Yeong Ahn1, Jin Kim1,2, Min A Kim2, Jiwoon Choi2, Woo Ho Kim3,2. 1. Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea. 2. Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea. 3. Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea woohokim@snu.ac.kr.
Abstract
BACKGROUND: Increased expression of hepatocyte growth factor (HGF) and MET proto-oncogene (c-MET) is associated with poor prognosis in various cancer types. Recently, it was reported that the expression of HGF induces resistance to tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor, human epidermal receptor receptor 2, and b-raf proto-oncogene. Here, we investigated the effects of HGF overexpression in gastric cancer cells in the absence or presence of c-MET TKIs. MATERIALS AND METHODS: The effects of c-MET TKIs in gastric cancer cells with and without c-MET overexpression were determined in gastric cancer cell lines with various cell biology methods. RESULTS: Compared to the control, cells with induced expression of HGF 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 in Hs746T cells. However, HGF-transfected cells were less affected. CONCLUSION: c-MET TKIs had inhibitory effects only on cells overexpressing c-MET. Furthermore, overexpression of HGF resulted in resistance to c-MET TKIs through an autocrine manner in gastric cancer cells. Copyright
BACKGROUND: Increased expression of hepatocyte growth factor (HGF) and MET proto-oncogene (c-MET) is associated with poor prognosis in various cancer types. Recently, it was reported that the expression of HGF induces resistance to tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor, human epidermal receptor receptor 2, and b-raf proto-oncogene. Here, we investigated the effects of HGF overexpression in gastric cancer cells in the absence or presence of c-MET TKIs. MATERIALS AND METHODS: The effects of c-MET TKIs in gastric cancer cells with and without c-MET overexpression were determined in gastric cancer cell lines with various cell biology methods. RESULTS: Compared to the control, cells with induced expression of HGF 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 in Hs746T cells. However, HGF-transfected cells were less affected. CONCLUSION:c-MET TKIs had inhibitory effects only on cells overexpressing c-MET. Furthermore, overexpression of HGF resulted in resistance to c-MET TKIs through an autocrine manner in gastric cancer cells. Copyright
Authors: Srinivasa P Pothula; Zhihong Xu; David Goldstein; Romano C Pirola; Jeremy S Wilson; Minoti V Apte Journal: Int J Mol Sci Date: 2020-12-01 Impact factor: 5.923
Authors: Melanie M Frigault; Aleksandra Markovets; Barrett Nuttall; Kyoung-Mee Kim; Se Hoon Park; Esha A Gangolli; Peter G S Mortimer; Simon J Hollingsworth; Jung Yong Hong; Kyung Kim; Seung Tae Kim; J Carl Barrett; Jeeyun Lee Journal: JCO Precis Oncol Date: 2020-03-24