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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2014 | Research

Store-operated Ca²⁺ entry regulates glioma cell migration and invasion via modulation of Pyk2 phosphorylation

Authors: Meng Zhu, Lei Chen, Pengfei Zhao, Hua Zhou, Chen Zhang, Shengping Yu, Yu Lin, Xuejun Yang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2014

Abstract

Background

The ubiquitous second messenger Ca²⁺ has been demonstrated to play an important role in cancer progression. Store-operated Ca²⁺ entry (SOCE) is the main Ca²⁺ entry pathway regulating intracellular Ca²⁺ concentration in a variety of cancer types. The present study aimed to explore the specific mechanisms of SOCE in the processes of glioma migration and invasion.

Methods

The expression of Orai1, a key component of SOCE, was examined in glioma samples and glioma cell lines by immunohistochemistry and western blot analysis. Both pharmacological intervention and RNA interference were employed to investigate the role of SOCE in glioma cell migration and invasion in vitro. The intracellular Ca²⁺ was certified through Fluo-4/AM based Ca²⁺ measurement. The effect of SOCE on cell viability, migration, and invasion was explored by methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, transwell invasion assay. Western blot analysis and immunofluorescence assay were used to observe the changes of downstream related protein and cell morpholog.

Results

Orai1 expression was elevated in glioma tissues and several glioma cell lines compared with non-neoplastic brain tissues. Either inhibition of SOCE by a pharmacological inhibitor or Orai1 downregulation suppressed glioma cell migration and invasion. However, re-expression of Orai1 could rescue glioma cell motility. Furthermore, phosphorylation of proline-rich tyrosine kinase 2 (Pyk2) participated in the mechanisms by which SOCE regulated focal adhesion turnover and epithelial-to-mesenchymal (−like) transition in glioma cells, both of which are considered to be critical for tumor progression.

Conclusions

The SOCE-Pyk2 pathway is essential for glioma migration and invasion. The study indicates the potential value of Orai1 as a molecular target for anti-invasion therapy.

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Title: Store-operated Ca2+ entry regulates glioma cell migration and invasion via modulation of Pyk2 phosphorylation
Authors: Meng Zhu
Lei Chen
Pengfei Zhao
Hua Zhou
Chen Zhang
Shengping Yu
Yu Lin
Xuejun Yang
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2014
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-014-0098-1

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Abstract

Background

Methods

Results

Conclusions

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