title: Knockdown of BAG3 induces epithelial-mesenchymal transition in thyroid cancer cells through ZEB1 activation.
abstract: The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial-mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppressor of E-cadherin, transcription factor ZEB1 is one of the key inducers of EMT, whose expression promotes tumorigenesis and metastasis of carcinomas. Bcl-2-associated athanogene 3 (BAG3) affects multifaceted cellular functions, including proliferation, apoptosis, cell adhesion and invasion, viral infection, and autophagy. Recently, we have reported a novel role of BAG3 implicated in EMT, while the mechanisms are poorly elucidated. The current study demonstrated that knockdown of BAG3 induced EMT, and increased cell migratory and invasiveness in thyroid cancer cells via transcriptional activation of ZEB1. We also found that BAG3 knockdown led to nuclear accumulation of β-catenin, which was responsible for the transcriptional activation of ZEB1. These results indicate BAG3 as a regulator of ZEB1 expression in EMT and as a regulator of metastasis in thyroid cancer cells, providing potential targets to prevent and/or treat thyroid cancer cell invasion and metastasis.
authors.affiliation: 1] Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China [2] Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors.forename: X
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
authors.forename: D-H
authors.initials: DH
authors.lastname: Kong
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Zong
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
authors.forename: B-Q
authors.initials: BQ
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, the 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Z-X
authors.initials: ZX
authors.lastname: Du
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors.forename: L
authors.initials: L
authors.lastname: Cao
authors.affiliation: 1] Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China [2] Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors.forename: H-Q
authors.initials: HQ
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D034622:RNA Interference; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051176:beta Catenin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; C495270:CTNNB1 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051176:beta Catenin