Store-operated Ca(2+) entry regulates glioma cell migration and invasion via modulation of Pyk2 phosphorylation.

Abstract

BACKGROUND:

The ubiquitous second messenger Ca(2+) has been demonstrated to play an important role in cancer progression. Store-operated Ca(2+) entry (SOCE) is the main Ca(2+) entry pathway regulating intracellular Ca(2+) 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 Ca(2+) was certified through Fluo-4/AM based Ca(2+) 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.

• Authors: Meng Zhu, Lei Chen, Pengfei Zhao, Hua Zhou, Chen Zhang, Shengping Yu, Yu Lin, Xuejun Yang
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 33 Pg. 98 (Nov 30 2014) ISSN: 1756-9966 [Electronic] England
• PMID: 25433371 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channels
• ORAI1 Protein
• ORAI1 protein, human
• Focal Adhesion Kinase 2
• PTK2B protein, human
• Calcium

Topics

• Brain Neoplasms (enzymology, genetics, pathology)
• Calcium (metabolism)
• Calcium Channels (genetics, metabolism)
• Calcium Signaling
• Cell Adhesion
• Cell Line, Tumor
• Cell Movement
• Epithelial-Mesenchymal Transition
• Focal Adhesion Kinase 2 (genetics, metabolism)
• Glioma (enzymology, genetics, pathology)
• Humans
• Neoplasm Invasiveness
• ORAI1 Protein
• Phosphorylation
• RNA Interference
• Time Factors
• Transfection