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A calcium-sensing receptor polymorphism at E942K promotes the proliferation of gastric cancer cells via Ca²⁺ and ERK1/2 pathways

ZHANG Ya-Bo¹, DU Chao², LU Cheng³, DONG Hui³, WU Xiao-Ling^1,*

¹Department of Digestive System, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China；²Department of Gastroenterology and Hepatology, Chengdu Military General Hospital, Chengdu 610038, China；³Department of Gastroenterology, Xinqiao Hospital, Second Affiliated Hospital of Army Medical University, Chongqing 400037, China

Abstract

The study was designed to investigate the effects and mechanism of a calcium-sensing receptor (CaSR) polymorphism at E942K on the proliferation of gastric cancer cells. 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 E942K mutant plasmid and wild-type (WT) plasmid into SGC-7901 and HEK-293 cells. The effect of E942K mutation on cell proliferation ability was detected by CCK8 and cell clone formation experiments. The effect of E942K mutation 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 β-catenin in downstream signaling pathways after E942K mutation. The results showed that the mutation rate of E942K in gastric cancer group was significantly higher than that in normal control group (P < 0.05). CCK8 and cell clone formation experiments showed that E942K mutation significantly improved the proliferation ability of SGC-7901 gastric cancer cells and HEK-293 cells. E942K mutation enhanced calcium signaling in SGC-7901 and HEK-293 cells. E942K mutation enhanced ERK1/2 phosphorylation without affecting β-catenin phosphorylation. The results suggest that E942K mutation in CaSR may ultimately promote the proliferation of gastric cancer cells by enhancing intracellular calcium signaling and ERK1/2 phosphorylation. These results have potential clinical implications for the diagnosis and targeted therapy of gastric cancer.

Key words: gastric cancer; polymorphism; calcium-sensing receptor; calcium signaling; proliferation; ERK1/2

Received: 2019-10-30　　Accepted: 2019-05-15

Corresponding author: 吴小翎　　E-mail: wuxiaoling@cqmu.edu.cn

DOI: 10.13294/j.aps.2020.0038

Citing This Article：

ZHANG Ya-Bo, DU Chao, LU Cheng, DONG Hui, WU Xiao-Ling. A calcium-sensing receptor polymorphism at E942K promotes the proliferation of gastric cancer cells via Ca²⁺ and ERK1/2 pathways. Acta Physiol Sin 2020; 72 (3): 274-284 (in Chinese with English abstract).