title: Effects of estrogen-related receptor alpha (ERRα) on proliferation and metastasis of human lung cancer A549 cells.
abstract: Estrogen-related receptor alpha (ERRα) plays an important role in the development of hormone-dependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects of ERRα on the proliferation and metastasis of lung cancer A549 cells. The mRNA and protein levels of ERRα were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by qRT-PCR and Western blotting, respectively. ERRα plasmid transfection and XCT-790 (an inverse agonist of ERRα) were used to up-regulate or down-regulate ERRα expression in A549 cells, respectively. The viability of A549 cells was measured by cell counting kit-8 (CCK-8) and the motility of A549 cells by wound healing assay and Transwell migration/invasion assay. The epithelial markers E-cadherin (E-Cad) and zona occludin-1 (ZO-1), the mesenchymal markers fibronectin (FN) and vimentin (Vim) and the transcription factors (Snail, Zeb1 Twist and Slug) were further detected at mRNA and protein levels by qRT-PCR and Western blotting, respectively. The results showed that ERRα promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly inhibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithelial-to-mesenchymal transition (EMT) of A549 cells, down-regulated the epithelial makers E-Cad and ZO-1, and up-regulated the mesenchymal makers FN and Vim. Silencing of Slug, but not other transcription factors, significantly abolished the ERRα-induced EMT of A549 cells. It was suggested that ERRα promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRα might be an efficient approach for lung cancer treatment.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Huang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Bao-Zhang
authors.initials: BZ
authors.lastname: Guan
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China. yin-yun@126.com.
authors.forename: Liang-Hong
authors.initials: LH
authors.lastname: Yin
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Fan-Na
authors.initials: FN
authors.lastname: Liu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Qi-Yi
authors.initials: QY
authors.lastname: Zheng
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Fo-Lan
authors.initials: FL
authors.lastname: Li
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Ying-Xue
authors.initials: YX
authors.lastname: Zhong
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005786:Gene Expression Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor