Calponin 3 promotes invasion and drug resistance of colon cancer cells

Abstract

BACKGROUND: Calponin 3 (CNN3) is an actin-binding protein expressed in smooth muscle and non-smooth muscle cells. It is required for cytoskeletal rearrangement and wound healing. AIM: To dissect the role of CNN3 in carcinogenesis with a focus on colon cancer. METHODS: A total of 20 cancer cell lines (8 breast, 11 colon, and HeLa cervical cancer cell as a positive control for mesenchymal phenotype) and 57 formalin-fixed, paraffin-embedded sections from archived sporadic colorectal carcinomas were included in this study. CNN3 expression analysis by western blot or immunohistochemistry was followed by functional analyses. The CNN3 gene was silenced by specific small interfering RNA (commonly known as siRNA), followed by confirmation of the silencing efficiency by western blotting. Then, the silenced cells and control siRNA-transfected cells were analyzed for changes in epithelial and mesenchymal markers, invasion, and response to 5-fluoruracil treatment. We also performed proteomics analysis using a phospho-kinase array-based panel of 45 proteins. RESULTS: . CONCLUSION: These results show the involvement of CNN3 in lymph node metastasis and resistance to chemotherapy in colon cancer and suggest that significant oncogenic pathways are involved in these CNN3-related actions.