title: MACC1 promotes carcinogenesis of colorectal cancer via β-catenin signaling pathway.
abstract: Here we confirmed that metastasis-associated in colon cancer 1 (MACC1) and β-catenin expression were higher in colorectal cancer (CRC) cells and tissues than those in normal colonic epithelial cell line and adjacent non-tumour colorectal mucosa (ANM) tissues, respectively. MACC1 expression was significantly related to histological differentiation (p<0.001), UICC stage (p=0.029), T classification (p=0.017), and N classification (p=0.023). Cox regression analysis demonstrated that high MACC1/abnormal β-catenin expression was the strongest independent prognostic indicator for reduced overall survival in CRC patients. Significant positive correlation between MACC1 expression and abnormal β-catenin expression was found in CRC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, colony formation, and tumorigenesis, both in vitro and in vivo, but induced apoptosis in CRC cells. Further MACC1 over-expression increased Met, β-catenin, and its downstream genes including c-Myc, cyclin D1, and MMP9 expression, and its upstream gene phos-GSK3β (Ser9) expression. In addition, MACC1 increased vimentin and suppressed E-cadherin in HCT116 cells. Silencing of MACC1 reversed all these changes. Our results firstly suggest that MACC1 plays an important role in carcinogenesis and progression of CRC through β-catenin signaling pathway and mesenchymal-epithelial transition.
authors.affiliation: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhen
authors.forename: Sujuan
authors.initials: S
authors.lastname: Dai
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Lili
authors.initials: L
authors.lastname: Kang
authors.forename: Huijuan
authors.initials: H
authors.lastname: Shi
authors.forename: Fenfen
authors.initials: F
authors.lastname: Zhang
authors.forename: Dongjie
authors.initials: D
authors.lastname: Yang
authors.forename: Shirong
authors.initials: S
authors.lastname: Cai
authors.forename: Yulong
authors.initials: Y
authors.lastname: He
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Anjia
authors.initials: A
authors.lastname: Han
mesh_terms: D000368:Aged; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C544162:MACC1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin