Calcium-sensing receptor bridges calcium and telomerase reverse transcriptase in gastric cancers via Akt
Calcium-sensing receptor bridges calcium and telomerase reverse transcriptase in gastric cancers via Akt
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钙敏感受体通过 Akt 桥接胃癌中的钙和端粒酶逆转录酶
DOI：
10.1007/s12094-019-02226-4
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发表时间：
2019-10
影响因子：
3.4
通讯作者：
Xu J.
中科院分区：
文献类型：
--
作者：
Xie R.;Tuo B.;Yang S.;Chen X. -Q.;Xu J.
目的人端粒酶逆转录酶(HTERT)和钙敏感受体(CaSR)在胃癌中起癌基因作用，但它们在胃癌发生发展中的关系尚不清楚。方法采用免疫组织化学方法对41例胃癌患者的临床资料进行hTERT和CaSR的检测。其中，5例患者的标本也进行了Western blotting分析。结果人胃癌细胞系MKN45和SGC-7901中hTERT和CaSR表达均呈正相关，胃癌细胞MKN45和SGC-7901中也存在这种现象。钙以CaSR依赖的方式在转录水平诱导hTERT的表达，随后端粒酶活性增加，因为CaSR shRNA或CaSR拮抗剂NPS2143取消了钙介导的hTERT和端粒酶活性的调节。进一步研究表明，CaSR介导的胞内钙升高和Akt激活参与了细胞外钙对hTERT的调节。结论CaSR与hTERT在胃癌的发生发展过程中存在功能关联，CaSR-hTERT偶联有望成为抗胃癌治疗的新靶点。
PurposeHuman telomerase reverse transcriptase (hTERT) and calcium-sensing receptor (CaSR) act as an oncogene in gastric cancers, however, their relationship in the progression of gastric cancers is yet to be elucidated. Herein, we aimed to access the potential interaction between hTERT and CaSR in the development of gastric cancers.MethodsThe clinical data of 41 patients with gastric cancers were analyzed regarding the expressions of hTERT and CaSR by immunohistochemistry. Among them, five patients’ specimens were also analyzed by Western blotting. The regulation of calcium on the expression level of hTERT and the possible underlying mechanism via CaSR were explored in gastric cancer cell lines MKN45 and SGC-7901.ResultsBoth hTERT and CaSR were increased and positively correlated in human gastric cancers, which also occurs in gastric cancer cells MKN45 and SGC-7901. Calcium induced hTERT expression at the transcriptional level in a CaSR-dependent manner followed by an increase in telomerase activity, as either a CaSR shRNA or the CaSR antagonist NPS2143 abolished the calcium-mediated regulation of hTERT and telomerase activity. Further studies showed that CaSR-mediated cytosolic calcium rise followed by Akt activation was involved in the regulation of hTERT by extracellular calcium. Finally, neither CaSR overexpression nor shRNA-mediated CaSR downregulation had an effect on the expression level of hTERT.ConclusionsOur findings established a functional linkage between CaSR and hTERT in the development of gastric cancers and CaSR–hTERT coupling might serve as a novel target for therapeutic strategy against human gastric cancers.
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DOI：
10.4103/1947-2714.170600
发表时间：
2015-11
期刊：
North American journal of medical sciences
影响因子：
--
作者：
Mirrakhimov AE
通讯作者：
Mirrakhimov AE
影响因子：
3.7
作者：
Lewis KA;Tollefsbol TO
通讯作者：
Tollefsbol TO
影响因子：
5.3
作者：
Koziel JE;Fox MJ;Steding CE;Sprouse AA;Herbert BS
通讯作者：
Herbert BS
影响因子：
4.6
作者：
Chou, Chao-Kai;Lee, Dung-Fang;Sun, Hui-Lung;Li, Long-Yuan;Lin, Chun-Yi;Huang, Wei-Chien;Hsu, Jung-Mao;Kuo, Hsu-Ping;Yamaguchi, Hirohito;Wang, Ying-Nai;Liu, Mo;Wu, Hsin-Yi;Liao, Pao-Chi;Yen, Chia-Jui;Hung, Mien-Chie
通讯作者：
Hung, Mien-Chie
影响因子：
3.5
作者：
Ramlee MK;Wang J;Toh WX;Li S
通讯作者：
Li S