Abstract：
:Although dietary calcium intake has long been recommended for disease prevention, the influence of calcium in development of cancer in the upper gastrointestinal tract has not been explored. Here, we assess the roles of calcium and calcium-sensing receptor (CaSR) in gastric cancer development. CaSR expression was enhanced in gastric cancer specimens, which positively correlated with serum calcium concentrations, tumor progression, poor survival, and male gender in gastric cancer patients. CaSR and transient receptor potential cation channel subfamily V member 4 (TRPV4) were colocalized in gastric cancer cells, and CaSR activation evoked TRPV4-mediated Ca2+ entry. Both CaSR and TRPV4 were involved in Ca2+-induced proliferation, migration, and invasion of gastric cancer cells through a Ca2+/AKT/β-catenin relay, which occurred only in gastric cancer cells or normal cells overexpressing CaSR. Tumor growth and metastasis of gastric cancer depended on CaSR in nude mice. Overall, our findings indicate that calcium may enhance expression and function of CaSR to potentially promote gastric cancer, and that targeting the novel CaSR/TRPV4/Ca2+ pathway might serve as preventive or therapeutic strategies for gastric cancer. Cancer Res; 77(23); 6499-512. ©2017 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Xie R,Xu J,Xiao Y,Wu J,Wan H,Tang B,Liu J,Fan Y,Wang S,Wu Y,Dong TX,Zhu MX,Carethers JM,Dong H,Yang Sdoi
10.1158/0008-5472.CAN-17-0360subject
Has Abstractpub_date
2017-12-01 00:00:00pages
6499-6512issue
23eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-17-0360journal_volume
77pub_type
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