STAT3 Targets ERR-α to Promote Epithelial-Mesenchymal Transition, Migration, and Invasion in Triple-Negative Breast Cancer Cells.

Autor:	Ma JH; School of Ocean, Shandong University, Weihai, P.R. China., Qi J; School of Pharmaceutical Sciences, Shandong University, Jinan, P.R. China., Lin SQ; School of Ocean, Shandong University, Weihai, P.R. China., Zhang CY; School of Ocean, Shandong University, Weihai, P.R. China., Liu FY; School of Ocean, Shandong University, Weihai, P.R. China., Xie WD; School of Ocean, Shandong University, Weihai, P.R. China., Li X; School of Ocean, Shandong University, Weihai, P.R. China. xiali@sdu.edu.cn.; School of Pharmaceutical Sciences, Shandong University, Jinan, P.R. China.; The Key Laboratory of Chemistry for Natural Product of Guizhou Province and Chinese Academy of Science, Guiyang, P.R. China.
Jazyk:	angličtina
Zdroj:	Molecular cancer research : MCR [Mol Cancer Res] 2019 Nov; Vol. 17 (11), pp. 2184-2195. Date of Electronic Publication: 2019 Aug 19.
DOI:	10.1158/1541-7786.MCR-18-1194
Abstrakt:	STAT3 is constitutively activated in many malignant tumor types and plays an important role in multiple aspects of cancer aggressiveness. In this study, we found that estrogen-related receptor α (ERR-α) correlating with STAT3 was highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues, which was associated with both the pathologic stage and prognosis of patients with TNBC. In vitro studies showed that ERR-α promoted TNBC cell migration and invasion, which was regulated by STAT3. Phosphorylated STAT3 (p-STAT3, Tyr 705) could bind to the promotor of ERR-α, and activate its transcription, which was suggested by luciferase assay and chromatin immunoprecipitation assay. We also found that ERR-α was the key target gene regulated by STAT3 in promoting epithelial-mesenchymal transition (EMT), migration, and invasion. ERR-α upregulated the expression of ZEB1, N-cadherin, and vimentin while downregulated the expression of E-cadherin. Furthermore, in vivo studies showed that ERR-α could increase the metastasis ability of TNBC. Our finding demonstrated that ERR-α was a direct regulatory gene target of p-STAT3, which was enriched for processes involving invasion and metastasis in TNBC and provided insight into TNBC pathogenesis, as well as a potential therapeutic option against TNBC metastasis. IMPLICATIONS: Our research first showed that p-STAT3 (Tyr 705) could bind to the promotor region of ERR-α and promote EMT in TNBC by ZEB1 pathways, thus providing a potential clinical target for TNBC. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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