Breast cancer metastasis suppressor 1 (BRMS1) attenuates TGF-β1-induced breast cancer cell aggressiveness through downregulating HIF-1α expression

BMC Cancer

Research Article

Do Yeun Cho¹  Chang Gyo Park²  Kyung Hwa Cho²  Seong-Lan Yu²  Hoi Young Lee² 

[1] Department of Hematology & Oncology, Myunggok Medical Institute, College of Medicine, Konyang University, Daejeon, Republic of Korea;Department of Pharmacology, Myunggok Medical Institute, College of Medicine, Konyang University, Daejeon, Republic of Korea;

关键词: BRMS1;    HIF-1α;    Snail;    TGF-β1;    TWIST1;   

DOI  :  10.1186/s12885-015-1864-y

 received in 2015-05-06, accepted in 2015-10-27,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundCancer metastasis is a multi-step event including epithelial-to-mesenchymal transition (EMT). Breast cancer metastasis suppressor 1 (BRMS1) is a novel metastasis suppressor protein without anti-proliferating activity. However, a detailed underlying mechanism by which BRMS1 attenuates cancer cell EMT and invasion remained to be answered. In the present study, we report an additional mechanism by which BRMS1 attenuates Transforming growth factor-beta1 (TGF-β1)-induced breast cancer cell EMT and invasion.MethodsExperimental analysis involving chromosome immunoprecipitation (ChIP) and luciferase reporter assays were used to validate hypoxia inducible factor-1alpha (HIF-1α) as a transcriptional regulator of TWIST1 and Snail. Quantitative RT-PCR was used to analyze transcript expression. Immunoblotting and immunofluorescence were used to analyze protein expression. Matrigel-coated in vitro invasion insert was used to analyze cancer cell invasion.ResultsBRMS1 strongly inhibited TGF-β1-induced breast cancer cell EMT and invasion. Unexpectedly, we observed that BRMS1 downregulates not only TWIST1 but also Snail expression, thereby inhibiting breast cancer cell invasion. In addition, we provide evidence that HIF-1α is required for Snail and TWIST1 expression. Further, BRMS1 reduced TGF-β1-induced HIF-1α transcript expression through inactivation of nuclear factor kappaB (NF-κB).ConclusionCollectively, the present study demonstrates a mechanical cascade of BRMS1 suppressing cancer cell invasion through downregulating HIF-1α transcript and consequently reducing Snail and TWIST1 expression.

【 授权许可】

CC BY   
© Cho et al. 2015