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Clinical and Translational Oncology

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24.10.2019 | Research Article

Calcium-sensing receptor bridges calcium and telomerase reverse transcriptase in gastric cancers via Akt

verfasst von: R. Xie, B. Tuo, S. Yang, X.-Q. Chen, J. Xu

Erschienen in: Clinical and Translational Oncology | Ausgabe 7/2020

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Abstract

Purpose

Human 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.

Methods

The 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.

Results

Both 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.

Conclusions

Our 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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Titel: Calcium-sensing receptor bridges calcium and telomerase reverse transcriptase in gastric cancers via Akt
verfasst von: R. Xie
B. Tuo
S. Yang
X.-Q. Chen
J. Xu
Publikationsdatum: 24.10.2019
Verlag: Springer International Publishing
Erschienen in: Clinical and Translational Oncology / Ausgabe 7/2020
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-019-02226-4

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Calcium-sensing receptor bridges calcium and telomerase reverse transcriptase in gastric cancers via Akt

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Purpose

Methods

Results

Conclusions

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