Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells

Oncology Letters
Dong Chul KimSun-Young Han

Abstract

Investigation of the mechanisms of resistance to targeted therapies is essential as resistance acquired during treatment may lead to relapse or refractoriness to the therapy. Our previous study identified the small molecule KRC-108 as a result of efforts to find an anticancer agent with c-Met-inhibitory activity. In the present study, the changes accompanying resistance to KRC-108 were investigated in the gastric cancer cell line MKN-45 and its KRC-108-resistant clones by western blot and immunofluorescence analyses. Increased expression of the c-Met protein was observed in KRC-108-resistant cells compared with that of the parental cells, and the phosphorylation of c-Met also increased in cell lines resistant to KRC-108. Resistance to the c-Met inhibitor was associated with cell morphological changes: MKN-45 parental cells, which had a round and poorly differentiated morphology, were altered to exhibit an epithelial cell-like phenotype in KRC-108-resistant clones. Consistent with the transition to an epithelial morphology, the expression of E-cadherin was increased in resistant cells. Using immunoprecipitation, an interaction between E-cadherin and the c-Met protein was observed in the KRC-108-resistant cells. Immunohistochemic...Continue Reading

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Citations

Apr 5, 2017·Nature Reviews. Clinical Oncology·Conor A BradleyUNKNOWN MErCuRIC consortium
Oct 8, 2016·Oncotarget·Qin-Nan ChenMing Sun
Jul 18, 2018·Molecular Medicine Reports·Jun Beom ParkJi Young Sul
Mar 29, 2020·Signal Transduction and Targeted Therapy·Yuan-Hong XieJing-Yuan Fang
Apr 17, 2020·Signal Transduction and Targeted Therapy·Yuan-Hong XieJing-Yuan Fang

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Methods Mentioned

BETA
dissection
pharmacotherapy
immunoprecipitation

Software Mentioned

GraphPad
SPSS
GraphPad Prism

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