Positive feedback loop of hepatoma-derived growth factor and β-catenin promotes carcinogenesis of colorectal cancer
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Jiayan Lian1,*, Jianming Tang1,*, Huijuan Shi1,*, Hui Li1, Tiantian Zhen1, Wenlin Xie1, Fenfen Zhang1, Yang Yang1 and Anjia Han1
1 Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
* These authors have contributed equally to this work
Anjia Han, email:
Keywords: hepatoma-derived growth factor, β-catenin, colorectal cancer
Received: May 30, 2015 Accepted: July 17, 2015 Published: July 22, 2015
To clarify the role of hepatoma-derived growth factor (HDGF) and β-catenin in carcinogenesis of colorectal cancer (CRC), our results showed that high HDGF expression was found in CRC cells and tissues and significantly related to histological differentiation (p = 0.035) and lymph node metastasis (p = 0.000). Significant positive correlation between HDGF expression and β-catenin abnormal expression was found in CRC tissues. High HDGF and lymph node metastasis were the strong independent prognostic indicators for reduced overall survival in CRC patients. HDGF knockdown dramatically inhibited cellular proliferation, migration, invasion, and tumorigenesis, both in vitro and in vivo, but induced G1 phase arrest and apoptosis in CRC cells. HDGF knock-down dramatically suppressed β-catenin and its down-stream genes expression in CRC cells. Intriguingly, β-catenin knock-down dramatically suppressed HDGF expression in CRC cells. Human recombinant Wnt3a and DKK1 treatment increased and decreased HDGF, β-catenin, c-Myc, cyclin D1, MMP9, and phos-GSK-3β (Ser9) protein expression in nuclear and cytoplasmic fraction of CRC cells upon β-catenin knock-down, respectively. Three HDGF-binding elements in β-catenin promoter were found and specific for transcriptional activation of β-catenin in CRC cells. In conclusion, our results first suggest that HDGF and β-catenin interacts as a positive feedback loop, which plays an important role in carcinogenesis and progression of CRC.
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