title: MTA3 regulates malignant progression of colorectal cancer through Wnt signaling pathway.
abstract: MTA3 overexpression has been implicated in carcinogenesis. The aim of the present study was to explore the clinical significance and biological roles of MTA3 in human colorectal cancer and colorectal cancer cells. A total of 80 cases of colorectal cancer tissues were examined by immunohistochemistry for MTA3 protein expression. We analyzed the relationship between MTA3 and clinical factors and the results showed that MTA3 was overexpressed in 51.25% (41/80) cancer cases. There was significant associations between MTA3 overexpression and advanced TNM stage (p = 0.0086) and Ki67 index (p = 0.001). We overexpressed MTA3 in LoVo cells and depleted its expression in HCT15 cells. The results showed that MTA3 promoted cancer cell proliferation, invasion, migration, and cell cycle progression, and inhibited 5-fluorouracil-induced apoptosis in LoVo cell line. MTA3 depletion in HCT15 cell line showed the opposite effects. In addition, we found that MTA3 positively regulated cell cycle proteins including cyclin D1 and cyclin E. It also upregulated Bcl2 and downregulated Bax expression. Furthermore, we found that MTA3 could activate Wnt signaling pathway by upregulating Wnt target proteins. Our results demonstrated that MTA3 overexpression contributes to colorectal cancer carcinogenesis, progression, and chemoresistance. MTA3 could serve as a potential therapeutic target in colorectal cancer.
authors.affiliation: Department of Gastroenterology and Endoscopy, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Taiwei
authors.initials: T
authors.lastname: Jiao
authors.affiliation: Department of Gastroenterology and Endoscopy, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gastroenterology and Endoscopy, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Tong
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology and Endoscopy, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology and Endoscopy, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology and Endoscopy, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology and Endoscopy, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology and Endoscopy, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019938:Cyclin D1 / Q000096:biosynthesis; D019927:Cyclin E / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009367:Neoplasm Staging; D015513:Oncogene Proteins / Q000096:biosynthesis; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; C486657:MTA3 protein, human; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D019938:Cyclin D1; D005472:Fluorouracil
keywords: MTA3; Wnt; colorectal cancer