癌变
钙敏感受体
癌症研究
信号转导
胰腺癌
钙信号传导
受体
钙
细胞生物学
生物
化学
内分泌学
内科学
医学
钙代谢
癌症
作者
Bo Tang,Jimmy Y.C. Chow,Hui Dong,Shi Yu Yang,Dehong Lu,John M. Carethers,Hui Dong
出处
期刊:Cancer Letters
[Elsevier]
日期:2016-07-10
卷期号:377 (1): 44-54
被引量:16
标识
DOI:10.1016/j.canlet.2016.04.027
摘要
The calcium sensing receptor (CaSR) is functionally expressed in normal human pancreases, but its pathological role in pancreatic tumorigenesis is currently unknown. We sought to investigate the role of CaSR in pancreatic cancer (PC) and the underlying molecular mechanisms. We revealed that the expression of CaSR was consistently downregulated in the primary cancer tissues from PC patients, which was correlated with tumor size, differentiation and poor survival of the patients. CaSR activation markedly suppressed pancreatic tumorigenesis in vitro and in vivo likely through the Ca(2+) entry mode of Na(+)/Ca(2+) exchanger 1 (NCX1) to induce Ca(2+) entry into PC cells. Moreover, NCX1-mediated Ca(2+) entry resulted in Ca(2+)-dependent inhibition of β-catenin signaling in PC cells, eventually leading to the inhibition of pancreatic tumorigenesis. Collectively, we demonstrate for the first time that CaSR exerts a suppressive function in pancreatic tumorigenesis through a novel NCX1/Ca(2+)/β-catenin signaling pathway. Targeting this specific signaling pathway could be a potential therapeutic strategy for PC.
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