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Content archived on 2024-05-29

Beta-catenin/TCF target gene programs driving intestinal Stem Cell maintenance, colorectal cancer initiation and progression


beta-catenin/TCF signalling in the intestinal epithelium controls colorectal cancer (CRC) initiation but also Stem Cell maintenance and specification. We have recently shown that paradoxically both processes are driven by the same genetic program. However, recent observations indicate that Wnt signalling might also direct a specific program in tumour cells, and that the core set of beta-catenin/TCF targets shared between CRC cells and intestinal Stem Cells is further modified throughout tumorigenesis. This project aims to the characterization of the beta-catenin/TCF target gene program that specifically drives the process of tumour formation in three steps; first, the identification and characterization of the different programs driven by beta-catenin/TCF in Stem Cells vs. CRC cells. Second, the study of modifications to such programs throughout tumorigenesis and the role of such modifications in tumour progression. Third, the characterization of the interaction between the program driven by beta-catenin/TCF and the TGF-beta pathway and its role in the acquisition of malignancy. New experimental set-ups including gene expression profiling of human tumours in combination with the study of new animal models will be instrumental in answering these questions. I expect that this work will represent a huge step forward in our understanding of the role of Wnt signalling in cancer and its relationship with the processes of Stem Cell maintenance.

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