Two-edged prognostic biomarker

09.07.10 Glasgow – Cancer cells can apparently switch their response to the tumour suppressor TGF-beta upon malignant transformation and make the cytokine act as a potent oncogene (J. Clin. Invest., doi: 10.1172/JCI136125). Together with colleagues, Adele Hannigan from the Beatson Institute for Cancer Research in Glasgow discovered that the effect is mediated by promotor methylation of the DAB2 gene in squamous cell carcinomas (SCC) and is a prognostic factor for metastasis. Hannigan carried out microarray analyses and found that low levels of DAB2 accompanied by high concentrations of TGF-beta correlated with poor prognosis. With a combination of gene silencing and immunohistochemical analyses, the researchers found that downregulation of DAB2 modulated the Smad/TGF-b pathway and blocked TGF-beta mediated inibition of cell proliferation and cell migration. Thus, DAB2 acts as a tumour suppressor in vivo and can be used as a prognostic biomarker for stratification of patients with squamous cell carcinoma.