title: STAT3 cooperates with Twist to mediate epithelial-mesenchymal transition in human hepatocellular carcinoma cells.
abstract: Epithelial-to-mesenchymal transition (EMT) is critical for the invasion and metastasis of hepatocellular carcinoma (HCC). However, to date, the association of signal transducer and activator of transcription 3 (STAT3) with EMT, and its mediated tumor invasion and metastasis in HCC, remain elusive. We investigated the relationship between STAT3 activation and EMT, and the underlying mechanisms involved in HCC progression. By stable transfection, we successfully overexpressed STAT3 in low metastatic SMMC7721 cells and silenced STAT3 expression in high metastatic MHCC97H cells. The EMT-associated molecular HCC cell changes were analyzed by real-time PCR, western blotting and immunocytochemical methods. The EMT-mediated HCC cell invasion and migration were evaluated by a Transwell cell invasion and cell migration assay, respectively. The interaction between STAT3 and Twist (a key EMT inducer) was evaluated by dual-luciferase reporter assay. In the present study, we found that STAT3 overexpression significantly reduced E-cadherin and β-cadherin, and it enhanced N-cadherin and vimentin expression in the SMMC7721 cells. STAT3 knockdown significantly increased E-cadherin and β-cadherin, and it decreased N-cadherin and vimentin expression in the MHCC97H cells. Meanwhile, a dual-luciferase reporter assay revealed that STAT3 may bind the Twist promoter, mediate its transcriptional activity, and then promote the EMT process in HCC cells. STAT3 activation-mediated EMT also evidently enhanced HCC cell invasion and migration. In summary, the present study demonstrated for the first time that STAT3 may cooperate with Twist to mediate EMT and induce HCC invasion and metastasis. Activated STAT3, Twist, and EMT markers may serve as potential molecular targets in the prevention and/or treatment of HCC invasion and metastasis.
authors: Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, P.R. China.
authors: Chuanhai
authors: C
authors: Zhang
authors: Department of Anesthesiology, Affiliated Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, P.R. China.
authors: Fenglin
authors: F
authors: Guo
authors: Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, P.R. China.
authors: Geliang
authors: G
authors: Xu
authors: Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, P.R. China.
authors: Jie
authors: J
authors: Ma
authors: Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, P.R. China.
authors: Feng
authors: F
authors: Shao
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D016297:Mutagenesis, Site-Directed; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D025941:Protein Interaction Mapping; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D051879:Twist-Related Protein 1 / Q000502:physiology*
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1