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New paper on WNT signaling in colorectal carcinoma

The canonical WNT signaling pathway is crucial for intestinal stem cell renewal and aberrant WNT signaling is an early event in colorectal cancer (CRC) development. A new report in the Journal Oncogene now shows for the first time that WNT2 is one of the most significantly induced genes in CRC stroma as compared to normal stroma. We identified cancer-associated fibroblasts (CAFs) as the main source of WNT2, which activated canonical signaling in colon cancer cells in a paracrine fashion. Furthermore, WNT2 activated autocrine canonical WNT signaling in primary fibroblasts, was associated with a pro-migratory and pro-invasive phenotype. The identification of the pro-malignant function of stromal derived WNT2 in CRC classifies WNT2 and its receptor as promising stromal targets to confine cancer progression in combination with conventional or targeted therapies.