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. Cx32 expression correlated with advanced FIGO staging,
differentiation and increased tumor size.
In CaCx
cell lines, Cx32 expression suppressed streptonigrin/cisplatin-induced apoptosis in
the absence of functional GJ. In CaCx specimens and cell lines, expression of Cx32
upregulated epidermal growth factor receptor (EGFR) expression. Inhibition of
EGFR signaling
abrogated the anti-apoptotic effect of Cx32 expression.
In conclusion, upregulated Cx32 in CaCx
cells produces anti-apoptotic, pro-tumorigenic effects in vivo and vitro.
Abnormal Cx32 expression/localization in CaCx appears to be both a mechanism and biomarker of
chemotherapeutic resistance.
Funding
This work was supported in part by below: the Joint Fund of the National Nature Science Foundation of China (contract No.U1303221), the National Natural Science Foundation of China (contract No. 81373439, 81473234), the grant for the construction of techn