Cross-talk between pRb/E2F and Wnt/beta-catenin pathways: E2F1 induces axin2 leading to repression of Wnt signalling and to increased cell death.
The pRb/E2F and Wnt/beta-catenin pathways are two of the most frequently deregulated pathways in human cancers. In this study, we show that E2F1 up-regulates the expression of axin2. Further, we show that axin2 can repress Wnt signalling leading to reduced cell growth and increased cell death. This represents cross-talk between major pathways involved in the formation of tumours. We use our data to suggest a novel mechanism for tumour suppression.
Hughes
Thomas A
TA
Molecular Haematology and Cancer Biology Unit, Camelia Botnar Laboratories, Institute of Child Health, University College London, London, UK.
Brady
Hugh J M
HJ
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins; D051176:beta Catenin
D018797:Cell Cycle Proteins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493755:E2f1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin