Cx31.1 acts as a tumour suppressor in non‐small cell lung cancer (NSCLC) cell lines through inhibition of cell proliferation and metastasis

Abstract

Reduced connexin expression and loss of gap junction function is a characteristic of many cancers, including lung cancer. However, there are little reports about the relation between Cx31.1 and lung cancer. This study was conducted to investigate the effect of Cx31.1 on non-small cell lung cancer (NSCLC). We found that the Cx31.1 was down-regulated in NSCLC cell lines, and the expression levels were reversely related with their metastatic potential. We ectopically expressed Cx31.1 in H1299 NSCLC cell line to examine the influence of Cx31.1 overexpression. The results showed that overexpression of Cx31.1 in H1299 cells reduced cell proliferation, induced a delay in the G1 phase, inhibited anchorage-independent growth and suppressed cell migration and invasion. The cell cycle delay and cell migration and invasion suppressive effects of Cx31.1 were partially reversed by siRNA targeting mRNA of Cx31.1. Moreover, xenografts of Cx31.1 overexpressing H1299 cells showed reduced tumourigenicity. These results suggested that Cx31.1 has tumour-suppressive properties. Further investigation indicated that cyclin D3 may be responsible for Cx31.1-induced G1 phase delay. Importantly, Cx31.1 increased the expression of epithelial markers, such as cytokeratin 18, and decreased expression of mesenchymal markers, such as vimentin, indicating a Cx31.1-mediated partial shift from a mesenchymal towards an epithelial phenotype. We concluded that Cx31.1 inhibit the malignant properties of NSCLC cell lines, the mechanisms under this may include regulation of EMT.

Influence of gap junction intercellular communication composed of connexin 43 on the antineoplastic effect of adriamycin in breast cancer cells

“…Cancer cells (including liver cancer, lung carcinoma and breast carcinoma) are generally linked to loss of connexin and/or GJIC (15,(31)(32)(33). Numerous studies have revealed the significant role of GJs in tumors, since recovered expression of connexin that forms GJs or recovered function of GJs could reduce the cell malignant phenotype (11,34,35).…”

Connexins, gap junctions and tissue invasion

“…Moreover, a recent study found that Cx31.1 may act on migration and invasion of lung cancer cells. In such a study, the overexpression of Cx31.1 in the lung cancer cells (H1299 cells) eliminates their 3D migration and invasion by inducing mesenchymal–epithelial transition (MET) [61].…”

The Association BetweenVEGF+936C/T and −634G/C Polymorphisms and Breast Cancer Susceptibility, Tumor Growth, and Metastases: Evidence From 20,728 Subjects

“…However, mutations in these genes account for only a minority of breast cancer and the exact molecular mechanisms underlying genetic susceptibility to this disease are still under intensive investigation. It is suggested that low-penetrance susceptibility genes combined with environmental factors may contribute to the development of cancer (6)(7)(8)(9)(10).…”