Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival
Menée à l'aide de lignées cellulaires, d'un modèle murin de cancer gastrique et de données du projet "The Cancer Genome Atlas", cette étude met en évidence un mécanisme par lequel les protéoglycanes transmembranaires SDC4 des vésicules extracellulaires favorisent la motilité et le processus invasif des cellules cancéreuses
Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.