Connexin32 activates necroptosis through Src-mediated inhibition of caspase 8 in hepatocellular carcinoma.

Necroptosis is an alternative form of programmed cell death that generally occurs under apoptosis-deficient conditions. Our previous work showed that connexin32 (Cx32) promotes the malignant progress of hepatocellular carcinoma (HCC) by enhancing the ability of resisting apoptosis in vivo and in vitro. Whether triggering necroptosis is a promising strategy to eliminate the apoptosis-resistant HCC cells with high Cx32 expression remains unknown.

Pattern of cell-to-cell transfer of microRNA by gap junction and its effect on the proliferation of glioma cells.

MicroRNA is expected to be a novel therapeutic tool for tumors. Gap junctions facilitate the transfer of microRNA, which exerts biological effects on tumor cells. However, the length of microRNA that can pass through certain gap junctions composed of specific connexin remains unknown.

Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication.

Analgesics and antineoplastic drugs are often used concurrently for cancer patients. Our previous study reported that gap junctions composed of connexin32 (Cx32) was implicated in the effect of analgesics on cisplatin cytotoxicity. However, the effect of analgesic on the most widely expressed connexin (Cx), connexin43 (Cx43), and whether such effect mediates the influence on chemotherapeutic efficiency remain unknown.

Cx32 suppresses extrinsic apoptosis in human cervical cancer cells via the NF‑κB signalling pathway.

Tumour necrosis factor α (TNFα) and TNF‑related apoptosis inducing ligand (TRAIL) usually trigger either survival or apoptosis signals in various cell types, and nuclear factor κB (NF‑κB) is a key factor that regulates their biological effects. Connexin 32 (Cx32) is a gap junction (GJ) protein that plays vital roles in tumourigenesis and tumour progression. Our previous study explored abnormal Cx32 expression in para‑nuclear areas, exacerbated prognostic parameters and suppressed streptonigrin/cisplatin-induced apoptosis in human cervical cancer (CaCx) cells.

Non-junctional Cx32 mediates anti-apoptotic and pro-tumor effects via epidermal growth factor receptor in human cervical cancer cells.

The role of connexin proteins (Cx), which form gap junctions (GJ), in progression and chemotherapeutic sensitivity of cervical cancer (CaCx), is unclear. Using cervix specimens (313 CaCx, 78 controls) and CaCx cell lines, we explored relationships among Cx expression, prognostic variables and mechanisms that may link them. In CaCx specimens, Cx32 was upregulated and cytoplasmically localized, and three other Cx downregulated, relative to controls.

The cytoplasmic translocation of Cx32 mediates cisplatin resistance in ovarian cancer cells.

Ovarian cancer is the most lethal gynecologic malignancy, and cisplatin is one of the first-line chemotherapeutic agents. However, acquired cisplatin resistance prevents the successful treatment of patients with ovarian cancer. Gap junction (GJ) and connexin (Cx) are closely related to tumor formation, but the relationship between cisplatin resistance and GJ or Cx are undetermined.

Different gap junction-propagated effects on cisplatin transfer result in opposite responses to cisplatin in normal cells versus tumor cells.

Previous work has shown that gap junction intercellular communication (GJIC) enhances cisplatin (Pt) toxicity in testicular tumor cells but decreases it in non-tumor testicular cells. In this study, these different GJIC-propagated effects were demonstrated in tumor versus non-tumor cells from other organ tissues (liver and lung). The downregulation of GJIC by several different manipulations (no cell contact, pharmacological inhibition, and siRNA suppression) decreased Pt toxicity in tumor cells but enhanced it in non-tumor cells.

Gap Junctions Enhance the Antiproliferative Effect of MicroRNA-124-3p in Glioblastoma Cells.

MicroRNA (miRNA) holds promise as a novel therapeutic tool for cancer treatment. However, the transfection efficiency of current delivery systems represents a bottleneck for clinical applications. Here, we demonstrate that gap junctions mediate an augmentative effect on the antiproliferation mediated by miR-124-3p in U87 and C6 glioblastoma cells.