Connexin 43 interacts with Bax to regulate apoptosis of pancreatic cancer through a gap junction-independent pathway

Sun,Yan; Zhao,Xiaoping; Yao,Yuting; Qi,Xinyi; Yuan,Yaozong; Hu,Yu

doi:10.3892/ijo.2012.1524

Connexin 43 interacts with Bax to regulate apoptosis of pancreatic cancer through a gap junction-independent pathway

Authors:
- Yan Sun
- Xiaoping Zhao
- Yuting Yao
- Xinyi Qi
- Yaozong Yuan
- Yu Hu
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Affiliations: Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Department of Biochemistry and Molecular Biology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, P.R. China, Department of Gastroenterology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, P.R. China
Published online on: June 20, 2012 https://doi.org/10.3892/ijo.2012.1524
Pages: 941-948

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Abstract

Connexins play important roles in many physiological and pathological processes. Although connexins are considered as tumor suppressors in several types of cancer, their roles in pancreatic cancer are unknown. In this study, we found that connexin 43 (Cx43) caused apparent apoptosis and growth inhibition in pancreatic cancer cells. The tumor-suppressive role of Cx43 was independent of the canonical gap junction pathway. In the context of apoptosis, Cx43 translocated to the mitochondria, where it interacted with Bax to initiate the mitochondrial apoptotic pathway. Following further examination of the Cx43 protein, we found that the 241-382aa region of Cx43 was required for interaction with Bax. Furthermore, this region was responsible for permeabilizing mitochondrial membrane potential. The results from the present study elucidate a novel mechanism of the Cx43-mediated regulation of apoptosis in pancreatic cancer.

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