Downregulated connexin32 promotes EMT through the Wnt/β-catenin pathway by targeting Snail expression in hepatocellular carcinoma

International Journal of Oncology
Yan YangQiong Wu

Abstract

Hepatocellular carcinoma (HCC) is one of the common malignances in the world and is associated with high mortality and poor prognosis, partly due to early invasion and metastasis. Cx32 has been indicated to be involved in the progression of many cancers including HCC, but its relationship with tumor invasion and metastasis is still controversial. In the present study, the downregulated Cx32 in HCC tissue was found negatively correlated with histological grade and lymph node metastasis. Cx32 regulated HCC migration and invasion in vitro and inhibited tumor metastasis in xenograft models in vivo. We subsequently identified that Cx32 mediated epithelial-mesenchymal transition (EMT) by regulating Snail expression, and the enhanced Snail was due to activation of Wnt/β-catenin signaling in response to Cx32 inhibition. Finally, decreased expression of Cx32 showed strong correlation with loss/reduction of E-cadherin, higher expression of Snail, and nuclear accumulation of β-catenin in HCC tissues. Taken together, our results suggest that Cx32 inhibits HCC invasion and metastasis through Snail-mediated EMT, Cx32 and this signaling pathway molecules may offer potential targets for HCC cancer therapy.

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Citations

Jun 30, 2019·Expert Review of Molecular Diagnostics·Shinichi UmedaYasuhiro Kodera
Apr 7, 2020·Current Pharmaceutical Design·Qiang LiuZhi-Xiang Yuan
Jul 2, 2020·OncoTargets and Therapy·Shidong ZhangShengkui Tan
Sep 13, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Asli AdakGulistan Mese
Dec 4, 2020·International Journal of Molecular Sciences·Magdalena NalewajskaAndrzej Pawlik

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Methods Mentioned

BETA
surgical resection
transfection
nuclear translocation

Software Mentioned

SPSS

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