Abstract
Deregulation of the pRb/E2F or Wnt/β-catenin pathway occurs frequently in human cancers, which is often associated with inappropriate cell proliferation. Although the oncogenic roles of pRb/E2F1 and Wnt/β-catenin pathways have been well studied, the functional interaction between the two pathways has only recently been characterized. In particular, E2F1 has been recently reported to negatively regulate Wnt/β-catenin activity in human colorectal cancers, though the mechanism underlying this regulation is not fully understood. Here we provide evidence that β-catenin interacting protein 1 (CTNNBIP1), also known as ICAT (inhibitor of β-catenin and TCF4), functions as a crucial node to mediate the cross talk between E2F1 and β-catenin signaling. We show that ICAT is a direct transcriptional target of E2F1, and that activation of ICAT by E2F1 is required for E2F1 to inhibit β-catenin activity. This study provides a mechanistic insight into the antagonistic interaction between E2F1 and β-catenin signaling.
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Acknowledgements
We thank Dr Kristian Helin (European Institute of Oncology, Milan) for the ER-E2F1 plasmids and Dr Claudio Brancolini for providing the IMR90/E1A cells. This work was supported by the Agency for Science, Technology and Research of Singapore.
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Wu, Z., Zheng, S., Li, Z. et al. E2F1 suppresses Wnt/β-catenin activity through transactivation of β-catenin interacting protein ICAT. Oncogene 30, 3979–3984 (2011). https://doi.org/10.1038/onc.2011.129
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DOI: https://doi.org/10.1038/onc.2011.129
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