Wnt signalling, Colorectalcancer, Tumour microenvironment
The central theme of our research is to understand how cell-to-cell communication controls growth and patterning in development and disease. The course of tumour progression is dictated by the dialogue between the cancer cells and tumour stroma. We want to understand the nature of this communication in the case of colorectal cancer.
Colorectal cancer (CRC) is the third leading cause of cancer death. Most cases arise as a consequence of the hyperactivation of the Wnt signaling pathway. This hyperactivation leads to deregulation of the stem cell pool. During normal epithelial homeostasis, stem cell differentiation and renewal are controlled by signals, such as Wnts, that are emitted from the stem cell niche. In the colon Gli1-expressing mesenchymal cells form the Wnt-producing niche; Gli1 expression is a marker of Hedgehog pathway activity. Underscoring the two-way nature of the conversation between the epitheliumand mesenchyme, the Hedgehog source appears to be the intestinal epithelial cells. We are analyzing the roles of both Hedgehog and Wnt signaling during intestinal epithelium homeostasis, during injury-induced regeneration, and during CRC progression. The aim is to understand how they contribute to the malignant growth of CRC.Publications