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

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.

DEP domain containing 1 predicts prognosis of hepatocellular carcinoma patients and regulates tumor proliferation and metastasis

“…mRNA levels showed that alteration of DEPDC1 expression significantly changed the expression of most of the selected genes in the SMCC‐7721 cells (Figure D), including NR4A2, SEPP1, EDN2, LYPD3, MMP9, WNT6, RAC2, WNT1, PTCH1 and CTNNB1. The oncogenic function of RAC2, NR4A2, MMP9 WNT1, PTCH1 and CTNNB1 has been reported in HCC . These results indicated that DEPDC1 may activate specific oncogenic signal pathways to promote HCC cell proliferation and metastasis.…”

“…The oncogenic function of RAC2, NR4A2, MMP9 WNT1, PTCH1 and CTNNB1 has been reported in HCC. [17][18][19][20][21][22] These results indicated that DEPDC1 may activate specific oncogenic signal pathways to promote HCC cell proliferation and metastasis.…”

The Role of Carcinogenesis-Related Biomarkers in the Wnt Pathway and Their Effects on Epithelial–Mesenchymal Transition (EMT) in Oral Squamous Cell Carcinoma

“…Yang Y et al [104] found that inhibition of Connexin 32 (Cx32) upregulates Snail expression via activation of Wnt/β-catenin signaling in Hepatocellular carcinoma (HCC). Moreover, with decreased expression of Cx32 and a reduction in E-cadherin, higher Snail expression and nuclear accumulation of β-catenin was observed in HCC tissues.…”

“…Excluding Cx32, one of the most efficient regulators of Snail is GSK-3β. Many signaling pathways mediated by growth factors regulate the function of Snail via GSK-3β, which is also involved in the regulation of the Wnt pathway [97,103,104].…”

2',3'‐Cyclic‐nucleotide 3'‐phosphodiesterase contributes to epithelial‐mesenchymal transition of lens epithelial cells through the notch signalling pathway

“…TGF‐β is considered the pivotal factor in inducing EMT during development, cancer and other pathological conditions. In some epithelial cell lines cultured in vitro, EMT can be induced by TGF‐β stimulation alone; furthermore, EMT is mediated by the Notch, Wnt/β‐catenin and integrin signalling pathways . Therefore, the regulation of EMT has been considered a therapeutic strategy to prevent the occurrence of ASC and PCO and to reduce the incidence of postoperative complications …”