Downregulation of estrogen-related receptor alpha inhibits human cutaneous squamous cell carcinoma cell proliferation and migration by regulating EMT via fibronectin and STAT3 signaling pathways

European Journal of Pharmacology
Hai-Fei ChenQun-Yi Li

Abstract

Estrogen-related receptor alpha (ERRα), one of orphan nuclear receptors, has been recently revealed as an oncogenic regulator in a variety of cancers. However, the linking gain of ERRα expression and cancer progression in cutaneous squamous cell carcinoma (cSCC) is largely unknown. Here, we showed that the mRNA and protein expression levels of ERRα were markedly higher in A431 cells compared with human keratinocyte cell line HaCaT, and targeted inhibition of ERRα by shRNA or its inverse agonist XCT790 significantly suppressed A431 cells proliferation and migration, while overexpression of ERRα promoted cell proliferation and migration. In addition, the data revealed that ERRα downregulation markedly inhibited the epithelial mesenchymal transition (EMT) of A431 cells with increasing the expression of E-cadherin and decreasing fibronectin (FN) and vimentin. Results from further experiments using Western blot suggested that ERRα suppression inhibited signal transducer and activator of transcription (STAT3) protein expression. In contrast, overexpression of ERRα promoted EMT and the activation of STAT3 pathway. Moreover, treatment with specific STAT3 inhibitor reversed EMT markers in ERRα-overexpressing A431 cells. In tumor xenogra...Continue Reading

Citations

Jul 20, 2019·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Xiao-Jie ChenGang Zhou
Apr 18, 2020·Technology in Cancer Research & Treatment·Ning An, Bo Zheng

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