A Calcium-sensing Receptor Polymorphism At E942K Promotes The Proliferation Of Gastric Cancer Cells Via Ca²⁺and ERK1/2 Pathways

Objective: The study was designed to investigate the effects and mechanism of a calcium-sensing receptor(CaSR)polymorphism at E942 K on the proliferation of gastric cancer cells.Methods: Single nucleotide polymorphisms(SNPs)were detected between gastric cancers group and normal controls group by DNA sequence analysis.The cell model was constructed by transfection of E942 K mutant plasmid and wild-type(WT)plasmid into SGC-7901 and HEK-293 cells.The effect of E942 K mutation on cell proliferation ability was detected by CCK8 and cell clone formation experiments.The effect of E942 K mutations on calcium signaling was detected by calcium imaging.Western blot experiments were used to detect changes in phosphorylation levels of key proteins ERK1/2 and ?-catenin in downstream signaling pathways after E942 K mutations.Results: The results showed that the mutation rate of E942 K in gastric cancer group was significantly higher than that in normal control group(P < 0.05).CCK8 and cell clone formation experiments showed that E942 K mutation significantly improved the proliferation ability of HEK-293 cells and SGC-7901 gastric cancer cells.E942 K mutations enhanced calcium signaling in HEK-293 and SGC-7901 cells.E942 K mutations enhanced ERK1/2 phosphorylation without affecting ?-catenin phosphorylation.Conclusion: E942 K mutations in CaSR may ultimately promote the proliferation of gastric cancer cells by enhancing intracellular calcium signaling and ERK1/2 phosphorylation.