title: Elevated Orai1 and STIM1 expressions upregulate MACC1 expression to promote tumor cell proliferation, metabolism, migration, and invasion in human gastric cancer.
abstract: ORAI calcium release-activated calcium modulator 1 (Orai1)- and stromal interacting molecule 1 (STIM1)-mediated store-operated Ca(2+) 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.
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jianling
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Oncology, Zhoushan Hospital, Zhoushan 316000, China.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Shaoting
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Na
authors.initials: N
authors.lastname: Huang
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
authors.affiliation: Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: nfyyliaowj@163.com.
authors.forename: Wangjun
authors.initials: W
authors.lastname: Liao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018572:Disease-Free Survival; D004734:Energy Metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D000071740:ORAI1 Protein / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000071737:Stromal Interaction Molecule 1 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C544162:MACC1 protein, human; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D015534:Trans-Activators; D014157:Transcription Factors
keywords: Gastric cancer; Metastasis-associated in colon cancer-1; ORAI calcium release-activated calcium modulator 1; Store-operated Ca(2+) entry; Stromal interacting molecule 1