title: Role of C9orf140 in the promotion of colorectal cancer progression and mechanisms of its upregulation via activation of STAT5, β-catenin and EZH2.
abstract: C9orf140 is a newly identified and characterized gene which is associated with cell proliferation and tumorigenicity. Expression of C9orf140 is upregulated in human gastric cancer and colorectal cancer (CRC); however, little is known about its role in CRC progression. We have investigated the clinical significance, biological effects and mechanisms of C9orf140 signaling. We found that the expression of C9orf140 is dramatically increased in a subset of CRC and correlates significantly with vascular invasion and lymph node metastasis. Our finding showed that knockdown of C9orf140 significantly reduced cell proliferation and invasion in vitro and dramatically increased overall survival and decreased lung metastasis in vivo. Conversely, overexpression of C9orf140 significantly increased lung metastasis and shortened overall survival when compared with control tumors. C9orf140-induced CRC cell invasion may depend on promoting the epithelial-mesenchymal transition progression. STAT5 may directly interact with the enhancer of zeste homolog 2 (EZH2) and β-catenin to enhance C9orf140 gene transactivation. Furthermore, C9orf140 may participate in cell invasion which is induced by STAT5, EZH2 or β-catenin activation. We describe the role of C9orf140 in CRC progression and find that C9orf140 overexpression may be regulated by STAT5, EZH2 and β-catenin interaction.
authors.affiliation: Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Weng
authors.affiliation: Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Ren
authors.affiliation: Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Laboratory of Molecular Oncology, Beijing Institute for Cancer Research, School of Oncology, Peking University, Hai-Dian District, Beijing, China.
authors.forename: You-Yong
authors.initials: YY
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease.
authors.forename: Hao-Yan
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease.
authors.forename: Xiong
authors.initials: X
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China and.
authors.forename: Wen-Xin
authors.initials: WX
authors.lastname: Qin
authors.affiliation: Department of Pathology & Medicine, The Warren Alpert Medical School of Brown University & Rhode Island Hospital, 55 Claverick St, Room 337, Providence, RI 02903, USA.
authors.forename: Weibiao
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease, fangjingyuan_new@163.com jiehong97@gmail.com wcao@hotmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease, fangjingyuan_new@163.com.
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011485:Protein Binding; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C000607889:SAPCD2 protein, human; D050799:STAT5 Transcription Factor; D051176:beta Catenin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2