title: STIM1 plays an important role in TGF-β-induced suppression of breast cancer cell proliferation.
abstract: Store-operated calcium entry (SOCE) signaling is involved in cancer progression. Stromal interaction molecule 1 (STIM1) triggers store-operated calcium channels to induce SOCE. Transforming growth factor-β (TGF-β) influences a wide range of cellular behaviors, including cell proliferation. However, little is known about the relationship between calcium signaling and TGF-β signaling in cancer cell proliferation. Here, we found that TGF-β induced cell cycle arrest at the G0/G1 phase and suppressed cell proliferation in MDA-MB-231 and MCF-7 breast cancer cells. These effects were impaired by extracellular Ca2+ chelator EGTA or SOCE specific inhibitor SKF96365 in MDA-MB-231 cells. Treating MDA-MB-231 cells with TGF-β for 24 and 48 h markedly decreased STIM1 expression and thapsigargin-induced SOCE. A transcriptional inhibitor of STIM1, Wilm's tumor suppressor 1 (WT1), was upregulated in TGF-β-treated MDA-MB-231 cells, and knockdown of WT1 expression partially restored the TGF-β-induced downregulation of STIM1. Stably overexpressing STIM1 in MDA-MB-231 cells restored the TGF-β-induced effects. The p21 mRNA level increased in SKF96365- or TGF-β-treated MDA-MB-231 cells, whereas that for cyclin E1 decreased. Our findings demonstrate for the first time that STIM1 and SOCE are involved in the TGF-β-induced suppression of cell proliferation. Furthermore, our studies also provide a new approach to inhibit breast cancer cell proliferation with small molecules targeting STIM1 and SOCE.
authors.affiliation: State Key Laboratory of Membrane Biology, Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Huanyi
authors.initials: H
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Membrane Biology, Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Membrane Biology, Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Renqing
authors.initials: R
authors.lastname: Feng
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D020013:Calcium Signaling / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D009363:Neoplasm Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D016212:Transforming Growth Factor beta
keywords: SOCE; STIM1; TGF-β; breast cancer; cell proliferation