title: Interaction with CCNH/CDK7 facilitates CtBP2 promoting esophageal squamous cell carcinoma (ESCC) metastasis via upregulating epithelial-mesenchymal transition (EMT) progression.
abstract: CtBP2, as a transcriptional corepressor of epithelial-specific genes, has been reported to promote tumor due to upregulating epithelial-mesenchymal transition (EMT) in cancer cells. CtBP2 was also demonstrated to contribute to the proliferation of esophageal squamous cell carcinoma (ESCC) cells through a negative transcriptional regulation of p16(INK4A). In this study, for the first time, we reported that CtBP2 expression, along with CCNH/CDK7, was higher in ESCC tissues with lymph node metastases than in those without lymph node metastases. Moreover, both CtBP2 and CCNH/CDK7 were positively correlated with E-cadherin, tumor grade, and tumor metastasis. However, the concrete mechanism of CtBP2's role in enhancing ESCC migration remains incompletely understood. We confirmed that CCNH/CDK7 could directly interact with CtBP2 in ESCC cells in vivo and in vitro. Furthermore, our data demonstrate for the first time that CtBP2 enhanced the migration of ESCC cells in a CCNH/CDK7-dependent manner. Our results indicated that CCNH/CDK7-CtBP2 axis may augment ESCC cell migration, and targeting the interaction of both may provide a novel therapeutic target of ESCC.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Soochow University, Suzhou, 215000, Jiangsu, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Junya
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Chengqi
authors.initials: C
authors.lastname: Guan
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Runzhou
authors.initials: R
authors.lastname: Ni
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Yuchan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Soochow University, Suzhou, 215000, Jiangsu, China. tianye_2014@126.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000368:Aged; D000429:Alcohol Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D056970:Co-Repressor Proteins; D056748:Cyclin H / Q000096:biosynthesis* / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis* / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: C534751:CCNH protein, human; D056970:Co-Repressor Proteins; D056748:Cyclin H; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009419:Nerve Tissue Proteins; D000429:Alcohol Oxidoreductases; C421248:CTBP2 protein, human; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C000722416:CDK7 protein, human
keywords: C-terminal binding protein 2 (CtBP2); Cyclin H (CCNH); Cyclin-dependent kinase 7 (CDK7); Epithelial-mesenchymal transition (EMT); Esophageal squamous cell carcinoma (ESCC); Metastasis
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