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Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells
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-inhibi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734112/ https://www.ncbi.nlm.nih.gov/pubmed/26893681 http://dx.doi.org/10.3892/ol.2015.4029 |
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author | KIM, DONG CHUL PARK, KYEONG RYANG JEONG, YEON JI YOON, HYONOK AHN, MI-JEONG RHO, GYU-JIN LEE, JONGKOOK GONG, YOUNG-DAE HAN, SUN-YOUNG |
author_facet | KIM, DONG CHUL PARK, KYEONG RYANG JEONG, YEON JI YOON, HYONOK AHN, MI-JEONG RHO, GYU-JIN LEE, JONGKOOK GONG, YOUNG-DAE HAN, SUN-YOUNG |
author_sort | KIM, DONG CHUL |
collection | PubMed |
description | 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. Immunohistochemical analysis of human gastric carcinoma tissues revealed the co-expression of E-cadherin and c-Met. These results suggest that the epithelial transition in KRC-108-resistant cells is mediated by recruiting E-cadherin to c-Met protein. Thus, the present study identified a mechanism used by cancer cells to confer resistance to anticancer agents. |
format | Online Article Text |
id | pubmed-4734112 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-47341122016-02-18 Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells KIM, DONG CHUL PARK, KYEONG RYANG JEONG, YEON JI YOON, HYONOK AHN, MI-JEONG RHO, GYU-JIN LEE, JONGKOOK GONG, YOUNG-DAE HAN, SUN-YOUNG Oncol Lett Articles 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. Immunohistochemical analysis of human gastric carcinoma tissues revealed the co-expression of E-cadherin and c-Met. These results suggest that the epithelial transition in KRC-108-resistant cells is mediated by recruiting E-cadherin to c-Met protein. Thus, the present study identified a mechanism used by cancer cells to confer resistance to anticancer agents. D.A. Spandidos 2016-02 2015-12-11 /pmc/articles/PMC4734112/ /pubmed/26893681 http://dx.doi.org/10.3892/ol.2015.4029 Text en Copyright: © Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles KIM, DONG CHUL PARK, KYEONG RYANG JEONG, YEON JI YOON, HYONOK AHN, MI-JEONG RHO, GYU-JIN LEE, JONGKOOK GONG, YOUNG-DAE HAN, SUN-YOUNG Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells |
title | Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells |
title_full | Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells |
title_fullStr | Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells |
title_full_unstemmed | Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells |
title_short | Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells |
title_sort | resistance to the c-met inhibitor krc-108 induces the epithelial transition of gastric cancer cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734112/ https://www.ncbi.nlm.nih.gov/pubmed/26893681 http://dx.doi.org/10.3892/ol.2015.4029 |
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