Cetuximab-Induced MET Activation Acts as a Novel Resistance Mechanism in Colon Cancer Cells
Year: 2014
Type: article
Abstract: Aberrant MET expression and hepatocyte growth factor (HGF) signaling are implicated in promoting resistance to targeted agents; however, the induced MET activation by epidermal growth factor receptor (EGFR) inhibitors mediating resistance to targeted therapy remains elusive. In this study, we identified that cetuximab-induced MET activation contributed to cetuximab resistance in Caco-2 colon cancer cells. MET inhibition or knockdown sensitized Caco-2 cells to cetuximab-mediated growth inhibition. Additionally, SRC activation promoted cetuximab resistance by interacting with MET. Pretreatment with SRC inhibitors abolished cetuximab-mediated MET activation and rendered Caco-2 cells sensitive to cetuximab. Notably, cetuximab induced MET/SRC/EGFR complex formation. MET inhibitor or SRC inhibitor suppressed phosphorylation of MET and SRC in the complex, and MET inhibitor singly led to disruption of complex formation. These results implicate alternative targeting of MET or SRC as rational strategies for reversing cetuximab resistance in colon cancer.
DOI: 10.3390/ijms15045838
Authors: Na Song, Shizhou Liu, Jingdong Zhang, Jing Liu, Ling Xu, Yunpeng Liu, Xiujuan Qu
Institution: First Hospital of China Medical University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Award: G8164829272
OpenAlex ID: W1981188685