P4-13 cMET promotes metastasis and epithelial-mesenchymal transition in colorectal carcinoma via repressing RKIP

Abstract

Colorectal cancer (CRC) ranks among the most frequent malignancies globally and is associated with high metastasis incidence. Today, it is becoming more prevalent among Asian populations, especially in the Chinese. There is increasing evidence that c-mesenchymal-epithelial transition factor (cMET) plays an important role in malignant progression, and its overexpression is closely linked with poor survival and enhanced resistance to drug therapy, hence abnormal cMET is viewed as a signature event in CRC. As a metastasis suppressor, loss of raf kinase inhibitory protein (RKIP) has been reported in many of cancer types. Both of them may serve to regulate CRC initiation and progression. It is therefore necessary to address the interaction between cMET/ERK signal axis and RKIP. In this study, expression of cMET and RKIP in CRC tissues and cell lines were determined, and their crosstalk and potential biological effects were explored using. Immunofluorescence staining and Chromatin immunoprecipitation. Our results showed cMET was inversely correlated with RKIP. Both cMET upregulation and RKIP downregulation implied poor clinical outcomes. Moreover, the MAPK/ERK signal pathway was involved in the regulation of cMET and RKIP. Overexpression of cMET promoted epithelial mesenchymal transition (EMT), invasion, migration and chemoresistance of tumor cells, whereas the impact could be efficiently impeded by increased RKIP. Notably, shRNA-mediated cMET knockdown dramatically suppressed cell proliferation, although no influence of RKIP on cell growth was observed in CRC. Altogether, cMET overexpression may contribute to tumor progression by inhibiting anti-oncogene RKIP, which provides preclinical justification for targeting RKIP to treat cMET-induced metastasis in CRC.