Paracrine interactions between epithelial cells promote colon cancer growth

Guillaume Jacquemin, Annabelle Wurmser, Mathilde Huyghe, Wenjie Sun, Meghan Perkins, Fairouz Qasrawi, Florent Dingli, Guillaume Arras, Damarys Loew, Silvia Fre

AbstractTumours are complex ecosystems composed of different types of cells that communicate and influence each other. While the critical role of stromal cells in affecting tumour growth is well established, the impact of mutant cancer cells on healthy surrounding tissues remains poorly defined. Here, we uncovered a paracrine mechanism by which intestinal cancer cells reactivate foetal and regenerative Yap-associated transcriptional programs in neighbouring wildtype epithelial cells, rendering them adapted to thrive in the tumour context. We identified the glycoprotein Thrombospondin-1 (THBS1) as the essential factor that mediates non-cell autonomous morphological and transcriptional responses. Importantly, Thbs1 is associated with bad prognosis in several human cancers. This study reveals the THBS1-YAP axis as the mechanistic link mediating paracrine interactions between epithelial cells in intestinal tumours.