CHN1 Promotes EMT via the Akt / GSK-3β / Snail Pathway in Cervical Carcinoma

Abstract

\n Background: Metastasis and invasion are key points to lead the mortality of cervical squamous cell carcinoma (CSCC). Epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationship between CHN1 and CSCC progression involved EMT has not been identified.Methods: The expression of CHN1 in CSCC tissues, adjacent tissues, and lymph node metastases of CSCC patients was detected by immunohistochemistry assay. Upregulation and knockdown of CHN1 was achieved by transfecting the plasmid into CSCC cells. The effect of CHN1 on proliferation was determined by CCK-8 and plate clone formation assay. Changes in migration and invasion capabilities were evaluated by scratch migration assay and trans-well invasion assay. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by measuring tumor weight and pathological analysis. The expression of EMT-related mRNA was measured by qRT-PCR assay in transfected CSCC cells. EMT-related proteins and Akt / GSK-3β / Snail signaling pathway-related proteins were also evaluated by using western blotting assay.Results: CHN1 was overexpression in CSCC tissues and was associated with lymph node metastasis and low survival of CSCC patients. The overexpression CHN1 promoted cell proliferation, migration and invasion bility in CSCC cells. On the contrary, silencing CHN1 inhibited these phenomena. In vivo experiments, the overexpression of CHN1 promoted tumors formed in xenograft tumor mouse model, with increased volume and weight of xenograft tumor. In addition, CHN1 induced the expression of EMT related transcription factors, accompanied by the decreased expression of epithelial markers and the increased expression of mesenchymal markers. The Akt / GSK-3β / Snail signaling pathway was activated by the overexpression of CHN1 in vitro, and the activation of the pathway was inhibited by signaling pathway inhibitor LY294002.Conclusion: These results suggest that CHN1 promoted development and progression in cervical carcinoma via of the Akt / GSK-3β / Snail pathway by inducing EMT.