Abstract 2636: Connexin 43 suppresses tumor angiogenesis by downregulation of vascular endothelial growth factor

Abstract

Abstract Gap junction intercellular communication (GJIC), which is performed by connexins, is crucial in the regulation of cellular functions. Connexin 43 (Cx43) is a general isoform expressed in most epithelial tissues especially in astrocytes. There were some studies indicated that Cx43 played a tumor suppressor which has been found in human tumors compared with adjacent normal tissues. Otherwise, there were some evidences showed that Cx43 overexpression affected metastasis. However, Cx43 plays a controversial role in tumor progression. Hypoxia, a hallmark of many solid tumors, is associated with angiogenesis and tumor progression. It activates a signal cascade that culminates in the stabilization of hypoxia-inducible factor 1 (HIF-1) transcription factor and activation of genes that possess hypoxia response elements (HRE). Herein, the loss of Cx43 was shown to stabilize HIF-1α, which is overexpressed in a majority of cancers and its overexpression correlates with poor prognosis and treatment failure. Meanwhile, we examined HIF-1α expression and activities in cancer cells with various Cx43 statuses. Loss of Cx43 expression in cancer cells resulted in increased HIF-1-dependent transcriptional activity and protein expression. In this study, we also found that Cx43 down-regulated VEGF and inhibited endothelial cell proliferation. Further work is warranted to understand the molecular mechanism leading to Cx43 effects by antiangiogenic signal pathway. Citation Format: Man-Chin Chen, Che-Hsin Lee. Connexin 43 suppresses tumor angiogenesis by downregulation of vascular endothelial growth factor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2636. doi:10.1158/1538-7445.AM2014-2636