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

  • Authors:
    • Dong Chul Kim
    • Kyeong Ryang Park
    • Yeon Ji Jeong
    • Hyonok Yoon
    • Mi‑Jeong Ahn
    • Gyu‑Jin Rho
    • Jongkook Lee
    • Young‑Dae Gong
    • Sun‑Young Han
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, School of Medicine, Gyeongsang National University, Jinju, Gyeongsang 52828, Republic of Korea, College of Pharmacy, Gyeongsang National University, Jinju, Gyeongsang 52828, Republic of Korea, Department of Theriogenology and Biotechnology, School of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsang 52828, Republic of Korea, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea, Innovative Drug Library Research Center, Dongguk University, Seoul 100‑715, Republic of Korea
    Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 991-997
    |
    Published online on: December 11, 2015
       https://doi.org/10.3892/ol.2015.4029
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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. 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.
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Copy and paste a formatted citation
Spandidos Publications style
Kim DC, Park KR, Jeong YJ, Yoon H, Ahn MJ, Rho GJ, Lee J, Gong YD and Han SY: Resistance to the c‑Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells. Oncol Lett 11: 991-997, 2016.
APA
Kim, D.C., Park, K.R., Jeong, Y.J., Yoon, H., Ahn, M., Rho, G. ... Han, S. (2016). Resistance to the c‑Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells. Oncology Letters, 11, 991-997. https://doi.org/10.3892/ol.2015.4029
MLA
Kim, D. C., Park, K. R., Jeong, Y. J., Yoon, H., Ahn, M., Rho, G., Lee, J., Gong, Y., Han, S."Resistance to the c‑Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells". Oncology Letters 11.2 (2016): 991-997.
Chicago
Kim, D. C., Park, K. R., Jeong, Y. J., Yoon, H., Ahn, M., Rho, G., Lee, J., Gong, Y., Han, S."Resistance to the c‑Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells". Oncology Letters 11, no. 2 (2016): 991-997. https://doi.org/10.3892/ol.2015.4029
Copy and paste a formatted citation
x
Spandidos Publications style
Kim DC, Park KR, Jeong YJ, Yoon H, Ahn MJ, Rho GJ, Lee J, Gong YD and Han SY: Resistance to the c‑Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells. Oncol Lett 11: 991-997, 2016.
APA
Kim, D.C., Park, K.R., Jeong, Y.J., Yoon, H., Ahn, M., Rho, G. ... Han, S. (2016). Resistance to the c‑Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells. Oncology Letters, 11, 991-997. https://doi.org/10.3892/ol.2015.4029
MLA
Kim, D. C., Park, K. R., Jeong, Y. J., Yoon, H., Ahn, M., Rho, G., Lee, J., Gong, Y., Han, S."Resistance to the c‑Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells". Oncology Letters 11.2 (2016): 991-997.
Chicago
Kim, D. C., Park, K. R., Jeong, Y. J., Yoon, H., Ahn, M., Rho, G., Lee, J., Gong, Y., Han, S."Resistance to the c‑Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells". Oncology Letters 11, no. 2 (2016): 991-997. https://doi.org/10.3892/ol.2015.4029
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