STIM1 overexpression promotes colorectal cancer progression, cell motility and COX-2 expression

被引:115
作者
Wang, J-Y [1 ,2 ,3 ,4 ]
Sun, J. [5 ]
Huang, M-Y [1 ,6 ,7 ]
Wang, Y-S [8 ]
Hou, M-F [1 ,6 ,7 ,9 ]
Sun, Y. [10 ]
He, H. [5 ]
Krishna, N. [5 ]
Chiu, S-J [1 ,11 ]
Lin, S. [5 ]
Yang, S. [5 ]
Chang, W-C [1 ,11 ,12 ,13 ]
机构
[1] Kaohsiung Med Univ Hosp, Ctr Canc, Kaohsiung, Taiwan
[2] Kaohsiung Med Univ Hosp, Div Gastrointestinal & Gen Surg, Kaohsiung, Taiwan
[3] Kaohsiung Med Univ, Coll Med, Grad Inst Clin Med, Dept Surg, Kaohsiung, Taiwan
[4] Kaohsiung Med Univ, Ctr Biomarkers & Biotech Drugs, Kaohsiung, Taiwan
[5] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Comprehens Melanoma Res Ctr,Dept Tumor Biol, Tampa, FL 33612 USA
[6] Kaohsiung Med Univ Hosp, Dept Radiat Oncol, Kaohsiung, Taiwan
[7] Kaohsiung Med Univ, Fac Med, Dept Radiat Oncol, Kaohsiung, Taiwan
[8] Kaohsiung Med Univ, Fac Med, Dept Genom Med, Kaohsiung, Taiwan
[9] Kaohsiung Municipal Tatung Hosp, Kaohsiung, Taiwan
[10] Tianjin Med Univ, Canc Inst & Hosp, Dept Pathol, Tianjin, Peoples R China
[11] Taipei Med Univ, Sch Pharm, Master Program Clin Pharmacogen & Pharmacoprote, Taipei, Taiwan
[12] Taipei Med Univ, Sch Pharm, Dept Clin Pharm, Taipei 110, Taiwan
[13] Taipei Med Univ, Wanfang Hosp, Dept Pharm, Taipei 110, Taiwan
关键词
OPERATED CALCIUM INFLUX; GENE ACTIVATION; CA2+ INFLUX; GROWTH; PROLIFERATION; MIGRATION; CHANNELS; FASCIN; ORAI1; INVOLVEMENT;
D O I
10.1038/onc.2014.366
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4358 / 4367
页数:10
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