HMGA1 Interacts with β-Catenin to Positively Regulate Wnt/β-Catenin Signaling in Colorectal Cancer Cells

• Published in: Pathology oncology research Vol. 20; no. 4; pp. 847 - 851
• Main Authors: Xing, Junjie, Cao, Guangwen, Fu, Chuangang
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.10.2014
• Subjects: Apoptosis; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; beta Catenin - metabolism; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cancer Research; Cell Proliferation; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Gene Expression Regulation, Neoplastic; HMGA1a Protein - metabolism; Humans; Immunoenzyme Techniques; Immunology; Oncology; Pathology; Signal Transduction; Transcription Factor 4; Transcription Factors - metabolism; Tumor Cells, Cultured; Wnt Proteins - metabolism; HMGA1; β-catenin; Wnt signaling pathway; Colorectal cancer
• ISSN: 1219-4956; 1532-2807
• DOI: 10.1007/s12253-014-9763-0

The high mobility group A1 (HMGA1) protein plays an important role in numerous biological processes, such as embryogenesis, cell proliferation, differentiation, apoptosis and carcinogenesis. Wnt/β-catenin signaling pathway plays a key role in development and cancer. Although previous reports have shown HMGA1 protein level can be induced by Wnt/β-catenin signaling pathway, however, the specific mechanism of HMGA1 on regulating Wnt/β-catenin signaling remains unclear. Here, we reported that HMGA1 interacted with β-catenin by using coimmunoprecipitation approach with exogenous and endogenous protein samples. HMGA1 positively regulated Wnt/β-catenin signaling, as determined by that HMGA1 increased the TOP-FLASH activity in a dose-dependent manner and β-catenin downstream target gene expression. Moreover, HMGA1 induced proliferation of colorectal cancer cells. Mechanistically, HMGA1 increased the β-catenin–TCF4 complex formation. Importantly, there was a correlation between HMGA1 and β-catenin expression in human colorectal cancer tissues. In summary, HMGA1 positively regulates Wnt/β-catenin signaling through interacting with β-catenin, which leads to increase the β-catenin–TCF4 complex formation. This suggests that targeting HMGA1 may be a useful therapeutic option in clinical application.