title: HMGA2 induces transcription factor Slug expression to promote epithelial-to-mesenchymal transition and contributes to colon cancer progression.
abstract: Epithelial-to-mesenchymal transition (EMT) is considered to play an essential role in progression and metastasis. This study aims to investigate the expression and underlying molecular targets of high-mobility group AT-hook 2 (HMGA2) in the progression of colon cancer. The expression of HMGA2 is upregulated by both active extracellular signal-regulated kinase (ERK)1/2 and TGF-β signaling in colon cancer cells through a series of lentiviral infection and pharmacological assays. HMGA2 knockdown by specific shRNAs attenuates proliferation, motility and invasion of colon cancer cells in vitro and in vivo. Besides, exogenous HMGA2 expression caused EMT in colon cancer cells, which was confirmed by the downregulation of the epithelial markers and the upregulation of the mesenchymal markers. Moreover, HMGA2 positively regulates the Slug expression by directly binding to the regulatory region in Slug promoter. Importantly, the knockdown of Slug could reverse the HMGA2-induced EMT and decrease the migration and invasion ability of colon cancer cells. Taken together, our results reveal a critical role for HMGA2 in promoting EMT, migration, invasion, and proliferation of colon cancer cells, suggesting HMGA2 as a potential molecular target to prevent colon cancer progression.
authors.affiliation: Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Zhongxin
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Radiology, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, China.
authors.forename: Chuanhui
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Electronic address: tiangengyou1999@hotmail.com.
authors.forename: Tiangeng
authors.initials: T
authors.lastname: You
mesh_terms: D000818:Animals; D001665:Binding Sites; D002465:Cell Movement; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D025743:HMGA2 Protein; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; C508960:TGFB1 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Epithelial-to-mesenchymal transition (EMT); HMGA2; Metastasis; Proliferation; Slug