title: STIM1 accelerates cell senescence in a remodeled microenvironment but enhances the epithelial-to-mesenchymal transition in prostate cancer.
abstract: The importance of store-operated Ca(2+) entry (SOCE) and the role of its key molecular regulators, STIM1 and ORAI1, in the development of cancer are emerging. Here, we report an unexpected dual function of SOCE in prostate cancer progression by revealing a decrease in the expression of STIM1 in human hyperplasia and tumor tissues of high histological grade and by demonstrating that STIM1 and ORAI1 inhibit cell growth by arresting the G0/G1 phase and enhancing cell senescence in human prostate cancer cells. In addition, STIM1 and ORAI1 inhibited NF-κB signaling and remodeled the tumor microenvironment by reducing the formation of M2 phenotype macrophages, possibly creating an unfavorable tumor microenvironment and inhibiting cancer development. However, STIM1 also promoted cell migration and the epithelial-to-mesenchymal transition by activating TGF-β, Snail and Wnt/β-Catenin pathways. Thus, our study revealed novel regulatory effects and the mechanisms by which STIM1 affects cell senescence, tumor migration and the tumor microenvironment, revealing that STIM1 has multiple functions in prostate cancer cells.
authors.affiliation: 1] School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China [2] State Key Lab of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Yingxi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, First Central Hospital Clinic Institute, Tianjin Medical University, 24 Fukang Road, Tianjin 300192 China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Niu
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Ye
authors.affiliation: School of Physics, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Hu
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.affiliation: Beijing Health Vocational College, 94 Nanhengxijie Street, Beijing, 100053 China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Luo
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, First Central Hospital Clinic Institute, Tianjin Medical University, 24 Fukang Road, Tianjin 300192 China.
authors.forename: Junying
authors.initials: J
authors.lastname: Li
authors.affiliation: 1] School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China [2] Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Tianjin 300071, China [3] Collaborative Innovation Center for Biotherapy, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: 1] School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China [2] Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Tianjin 300071, China [3] Collaborative Innovation Center for Biotherapy, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016922:Cellular Senescence; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000071740:ORAI1 Protein; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D000071737:Stromal Interaction Molecule 1; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071250:Snail Family Transcription Factors; D000071737:Stromal Interaction Molecule 1; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D051176:beta Catenin