MACC1 promotes carcinogenesis of colorectal cancer via β-catenin signaling pathway
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Tiantian Zhen1,*, Sujuan Dai1,*, Hui Li1,*, Yang Yang1,*, Lili Kang1, Huijuan Shi1, Fenfen Zhang1, Dongjie Yang2, Shirong Cai2, Yulong He2, Yingjie Liang1 and Anjia Han1
1 Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
2 Department of Gastrointestinal Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
* These authors contributed equally to this work
Anjia Han, email:
Keywords: MACC1, β-catenin, colorectal cancer, carcinogenesis
Received: February 7, 2014 Accepted: May 18, 2014 Published: May 20, 2014
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.
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