Epigenetic downregulation of human disabled homolog 2 switches TGF-beta from a tumor suppressor to a tumor promoter.

Journal article

The cytokine TGF-beta acts as a tumor suppressor in normal epithelial cells and during the early stages of tumorigenesis. During malignant progression, cancer cells can switch their response to TGF-beta and use this cytokine as a potent oncogenic factor; however, the mechanistic basis for this is poorly understood. Here we demonstrate that downregulation of disabled homolog 2 (DAB2) gene expression via promoter methylation frequently occurs in human squamous cell carcinomas (SCCs) and acts as...

Expand abstract

Authors: Hannigan, A; Smith, P; Kalna, G; Lo Nigro, C; Orange, C

• Publication status: Published
• Journal: Journal of clinical investigation
• Volume: 120
• Issue: 8
• Pages: 2842-2857
• Publication date: 2010-08-01
• DOI: 10.1172/jci36125
• EISSN: 1558-8238
• ISSN: 0021-9738
• Language: English
• Keywords: Smad2 Protein; Smad3 Protein; Head and Neck Neoplasms; Mice; Carcinoma, Squamous Cell; Transforming Growth Factor beta; Animals; Epigenesis, Genetic; DNA Methylation; Adaptor Proteins, Signal Transducing; Cell Line, Tumor; Tumor Suppressor Proteins; CpG Islands; Humans; Cell Movement; Down-Regulation; Promoter Regions, Genetic