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Cancer Res. 2017 Dec 1;77(23):6499-6512. doi: 10.1158/0008-5472.CAN-17-0360. Epub 2017 Sep 26.

Calcium Promotes Human Gastric Cancer via a Novel Coupling of Calcium-Sensing Receptor and TRPV4 Channel.

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Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Department of Gastroenterology, Affiliated Hospital to Zunyi Medical College, Zunyi, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Department of Medicine, University of California, San Diego, California.
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, Texas.
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.


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.

[Indexed for MEDLINE]

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