STIM1 Overexpression Promotes Colorectal Cancer Progression, Cell Motility and COX-2 Expression

Abstract

Tumor metastasis is the major cause of death among cancer patients, with >90% of cancer-related death attributable to the spreading of metastatic cells to secondary organs. Store-operated Ca2+ entry (SOCE) is the predominant Ca2+ entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca2+ sensor for store-operated channels. Here we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients. STIM1 overexpression in CRC was significantly associated with tumor size, depth of invasion, lymph node metastasis status and serum levels of carcinoembryonic antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility, while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our data further suggested that STIM1 promoted CRC cell migration through increasing the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2 with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In short, our data provided clinicopathological significance for STIM1 and SOCE in CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated metastasis with COX-2 inhibitors.

DOI: 10.1038/onc.2014.366

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@inproceedings{Wang2015STIM1OP, title={STIM1 Overexpression Promotes Colorectal Cancer Progression, Cell Motility and COX-2 Expression}, author={Jaw-Yuan Wang and Jianwei Sun and Ming-Yii Huang and Yu-Shiuan Wang and Ming-Feng Hou and Yan Sun and Huifang He and Niveditha Krishna and Siou-Jin Chiu and Shengchen Lin and Shengyu Yang and Wei-chiao Chang}, booktitle={Oncogene}, year={2015} }