Connexin 43 interacts with Bax to regulate apoptosis of pancreatic cancer             through a gap junction-independent pathway.
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.
Department of Geriatrics, Zhongshan Hospital, Fudan University,                     Shanghai 200032, P.R. China.
Yan
Y
Sun
Xiaoping
X
Zhao
Yuting
Y
Yao
Xinyi
X
Qi
Yaozong
Y
Yuan
Yu
Y
Hu
D017209:Apoptosis; D002450:Cell Communication; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018031:Connexin 43 / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D018031:Connexin 43; C500216:GJA1 protein, human; D051028:bcl-2-Associated X Protein