title: Estrogen-related receptor α participates transforming growth factor-β (TGF-β) induced epithelial-mesenchymal transition of osteosarcoma cells.
abstract: Osteosarcoma patients often exhibit pulmonary metastasis, which results in high patient mortality. Understanding the mechanisms of advanced metastasis in osteosarcoma cell is important for the targeted treatment and drug development. Our present study revealed that transforming growth factor-β (TGF-β) treatment can significantly promote the in vitro migration and invasion of human osteosarcoma MG-63 and HOS cells. The loss of epithelial characteristics E-cadherin (E-Cad) and up regulation of mesenchymal markers Vimentin (Vim) suggested TGF-β induced epithelial-mesenchymal transition (EMT) of osteosarcoma cells. TGF-β treatment obviously increased the expression of Snail, a key EMT-related transcription factor, in both MG-63 and HOS cells. Silencing of Snail markedly attenuated TGF-β induced down regulation of E-cad and up regulation of Vim. TGF-β treatment also significantly increased the expression and nuclear translocation of estrogen-related receptors α (ERRα), while had no obvious effect on the expression of ERα, ERβ, or ERRγ. Knock down of ERRα or its inhibitor XCT-790 significantly attenuated TFG-β induced EMT and transcription of Snail in osteosarcoma cells. Collectively, our present study revealed that TGF-β treatment can trigger the EMT of osteosarcoma cells via ERRα/Snail pathways. Our data suggested that ERRα/Snail pathways might be potential therapeutic targets of metastasis of osteosarcoma cells.
authors.affiliation: a Orthopaedics Department , Sun Yat-sen Memorial Hospital, Sun Yat-sen Unviersity , Yuexiu District , Guangzhou , China.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen Unviersity , Yuexiu District , Guangzhou , China.
authors.forename: Kunshui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: c Pediatric Hematology & Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , Guangzhou , China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: d SICU Department , Sun Yat-sen Memorial Hospital, Sun Yat-sen Unviersity , Yuexiu District, Guangzhou , China.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism*; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D011960:Receptors, Estrogen; D000071250:Snail Family Transcription Factors; D016212:Transforming Growth Factor beta; D000097983:ERRalpha Estrogen-Related Receptor
keywords: EMT; ERRα; Snail; TGF-β; osteosarcoma