Oncotarget

Research Papers:

STIM1 plays an important role in TGF-β-induced suppression of breast cancer cell proliferation

Huanyi Cheng _, Shiqiang Wang and Renqing Feng

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Oncotarget. 2016; 7:16866-16878. https://doi.org/10.18632/oncotarget.7619

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Abstract

Huanyi Cheng1, Shiqiang Wang1, Renqing Feng1

1State Key Laboratory of Membrane Biology, Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing 100871, China

Correspondence to:

Renqing Feng, e-mail: rqfeng@pku.edu.cn

Keywords: TGF-β, SOCE, STIM1, cell proliferation, breast cancer

Received: September 30, 2015     Accepted: February 11, 2016     Published: February 23, 2016

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.


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