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Calcium Promotes Human Gastric Cancer via a Novel Coupling of Calcium-Sensing Receptor and TRPV4 Channel
- Source :
- Cancer Research. 77:6499-6512
- Publication Year :
- 2017
- Publisher :
- American Association for Cancer Research (AACR), 2017.
-
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.
- Subjects :
- Male
0301 basic medicine
TRPV4
Cancer Research
medicine.medical_specialty
Carcinogenesis
Transplantation, Heterologous
Mice, Nude
TRPV Cation Channels
chemistry.chemical_element
Biology
Calcium
Metastasis
Mice
03 medical and health sciences
0302 clinical medicine
Cell Movement
Stomach Neoplasms
Cell Line, Tumor
Internal medicine
medicine
Animals
Humans
Protein kinase B
beta Catenin
Cell Proliferation
Cell Cycle
Cancer
medicine.disease
Rats
030104 developmental biology
Endocrinology
Oncology
chemistry
Tumor progression
030220 oncology & carcinogenesis
Cancer cell
Disease Progression
Calcium-sensing receptor
Proto-Oncogene Proteins c-akt
Receptors, Calcium-Sensing
Neoplasm Transplantation
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 77
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....0a875597d46367b529cf46df8559f873