The prognostic significance of CMTM3 in colorectal cancer and association with the phenomenon of EMT

Abstract

CKLF-like MARVEL transmembrane domain containing 3 (CMTM3), which is located at the critical tumor suppressor locus 16q22.1, has been proposed as a putative tumor suppressor gene in multiple types of malignancies. However, its role in colorectal cancer (CRC) has not been clearly defined. In this study, the potential relationships between CMTM3 and epithelial-mesenchymal transition (EMT)-related proteins were firstly analyzed in the clinical tissues. Our data demonstrated that CMTM3 presented a relatively negative staining in 130 CRC tissues, compared to their corresponding normal-appearing tissues (NATs) (P < 0.05). The reduction of CMTM3 protein was associated with the advanced depth of invasion, distant metastasis and tumor stage (P < 0.05). CRC patients with low CMTM3 levels had a poorer 5-year overall survival (OS) rate (P = 0.035), and the decreased level of CMTM3 could be served as an independent and significant prognostic factor of CRC patients (P = 0.013). Meanwhile, a significant positive relationship between CMTM-3 and E-cadherin was found (r = 0.253, P = 0.004), whereas CMTM3 negatively correlated with Vimentin (r = −0.506 P = 0.000). To better understand the tumor suppressing effect of CMTM3 in CRC progression through an EMT-dependent mechanism, we found that up-regulation of CMTM3 significantly suppressed the abilities of cell proliferation, migration and invasion in CRC cells in vitro (P < 0.05). The results of western blot analysis also disclosed that CMTM3 influenced the expressions of EMT-related proteins (E-cadherin, N-cadherin and Vimentin) (P < 0.05). These results suggested that CMTM3 might be involved in the EMT process of CRC, and could be considered as a potentially important molecular treatment strategy for early stage CRC patients.