22/01/2019
Koliaraki et al. from the Kollias and Koliaraki labs demonstrate that innate sensing through mesenchymal TLR4/MyD88 signals promotes spontaneous intestinal tumorigenesis. Genetic deletion of TLR4 or MyD88 in IMCs led to altered molecular profiles and reduction of intestinal tumors in the APCmin model. Ex vivo analysis in IMCs indicated that these effects are mediated through downstream signals involving growth factors, inflammatory and ECM-regulating genes, also found in human cancer-associated fibroblasts (CAFs). Their results provide the first direct evidence that during tumorigenesis, IMCs and CAFs are activated by innate TLR4/MyD88-mediated signals and respond to promote carcinogenesis in the intestine. These immuno-modulatory and pro-tumorigenic roles of mesenchymal cells offer exciting new links between tissue homeostasis, inflammation and cancer and could prove essential for the discovery of novel mechanisms in cancer pathogenesis, and patient stratification and treatment. [Pubmed]