Elevated Orai1 and STIM1 expressions upregulate MACC1 expression to promote tumor cell proliferation, metabolism, migration, and invasion in human gastric cancer

详细信息    查看全文

• 作者：Jianling Xia^a ; Hongqiang Wang^a ; ^b ; Hongxiang Huang^a ; Li Sun^a ; Shaoting Dong^a ; Na Huang^a ; Min Shi^a ; Jianping Bin^c ; Yulin Liao^c ; Wangjun Liao^a ; ^{nfyyliaowj@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ORAI calcium release-activated calcium modulator 1 ; Stromal interacting molecule 1 ; Store-operated Ca2+ entry ; Metastasis-associated in colon cancer-1 ; Gastric cancer
• 刊名：Cancer Letters
• 出版年：2016
• 出版时间：10 October 2016
• 年：2016
• 卷：381
• 期：1
• 页码：31-40
• 全文大小：4489 K

文摘

ORAI calcium release-activated calcium modulator 1 (Orai1)- and stromal interacting molecule 1 (STIM1)-mediated store-operated Ca²⁺ entry (SOCE) have been increasingly implicated in tumor progression; however, its role in gastric cancer (GC) is not well elucidated. We aimed to determine whether SOCE influences GC prognosis and elucidate the underlying mechanisms. Orai1 and STIM1 expressions were higher in GC tissues compared to adjacent non-tumor tissues according to RT-PCR and western blotting. Higher Orai1 and/or STIM1 expression was associated with more advanced disease, more frequent recurrence, and higher mortality rates in our study of 327 GC patients. The disease-free survival rates of Stage I–III patients and the overall survival rates of Stage IV patients were significantly worse when the tumors had high Orai1 and/or STIM1 expressions. Orai1 and/or STIM1 knockdown caused significantly reduced tumor growth and metastasis in athymic mice. Orai1 and/or STIM1 knockdown lowered the proliferation, metabolism, migration, and invasion of two GC cell lines. Also, Orai1 and/or STIM1 knockdown changed the markers of the cell cycle and epithelial-mesenchymal transition (EMT). These effects were reversed by metastasis-associated in colon cancer-1 (MACC1) overexpression. In summary, the composite molecules of SOCE suggest a poor prognosis for GC by promoting tumor cell proliferation, metabolism, migration, and invasion by targeting MACC1.