| Literature DB >> 30692637 |
Bo Tang1,2, Jilin Wu3,4, Michael X Zhu3,5, Xuemei Sun1, Jingjing Liu1, Rui Xie1,6, Tobias Xiao Dong2, Yufeng Xiao1, John M Carethers7, Shiming Yang8, Hui Dong9,10.
Abstract
Although VPAC1 and its ligand vasoactive intestinal peptide (VIP) are important in gastrointestinal physiology, their involvements in progression of gastrointestinal tumor have not been explored. Here, we found that higher expression of VIP/VPAC1 was observed in gastric cancer compared to the adjacent normal tissues. The increased expression of VIP/VPAC1 in gastric cancer correlated positively with invasion, tumor stage, lymph node, distant metastases, and poor survival. Moreover, high expression of VIP and VPAC1, advanced tumor stage and distant metastasis were independent prognostic factors. VPAC1 activation by VIP markedly induced TRPV4-mediated Ca2+ entry, and eventually promoted gastric cancer progression in a Ca2+ signaling-dependent manner. Inhibition of VPAC1 and its signaling pathway could block the progressive responses. VPAC1/TRPV4/Ca2+ signaling in turn enhanced the expression and secretion of VIP in gastric cancer cells, enforcing a positive feedback regulation mechanism. Taken together, our study demonstrate that VPAC1 is significantly overexpressed in gastric cancer and VPAC1/TRPV4/Ca2+ signaling axis could enforce a positive feedback regulation in gastric cancer progression. VIP/VPAC1 may serve as potential prognostic markers and therapeutic targets for gastric cancer.Entities:
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Year: 2019 PMID： 30692637 DOI： 10.1038/s41388-019-0709-6
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867