title: Positive feedback loop of hepatoma-derived growth factor and β-catenin promotes carcinogenesis of colorectal cancer.
abstract: 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.
authors: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Jiayan
authors: J
authors: Lian
authors: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Jianming
authors: J
authors: Tang
authors: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Huijuan
authors: H
authors: Shi
authors: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Hui
authors: H
authors: Li
authors: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Tiantian
authors: T
authors: Zhen
authors: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Wenlin
authors: W
authors: Xie
authors: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Fenfen
authors: F
authors: Zhang
authors: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Yang
authors: Y
authors: Yang
authors: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Anjia
authors: A
authors: Han
mesh_terms: D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018450:Disease Progression; D025461:Feedback, Physiological; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D034622:RNA Interference; D000067492:RNAi Therapeutics; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051176:beta Catenin; C051610:hepatoma-derived growth factor
keywords: colorectal cancer; hepatoma-derived growth factor; β-catenin