Integrin alpha-2 popped up in a screen of aggressive and chemoresistant PDAC cancers. In this study of Alessandro and Cecilia we validated the results we obtained in the RNA screen with various methods. Again we find a correlation between cell mechanics, aggressiveness, and chemoresistance. More to come …
Prognostic Significance of Integrin Subunit Alpha 2 (ITGA2) and Role of Mechanical Cues in Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma (PDAC).
Gregori, A.; Bergonzini, C.; Capula, M.; Mantini, G.; Khojasteh-Leylakoohi, F.; Comandatore, A.; Khalili-Tanha, G.; Khooei, A.; Morelli, L.; Avan, A.; Danen, E.H.; Schmidt, T.; Giovannetti, E.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and chemoresistant cancer, with a poor overall survival. The stiff stroma surrounding PDAC is known to be involved in chemoresistance via mechanical cues, although the mechanisms behind it are poorly understood. Here, we investigated whether integrin alpha 2 (ITGA2), a mechanical sensor of stiffness, correlated with poor prognosis and whether matrix stiffness could trigger chemoresistance to gemcitabine. By assessing two cohorts of patients, we observed a poorer prognosis for the high ITGA2 expression group. An increase in matrix stiffness prompted cancer cells to express more ITGA2 and become chemoresistant. ITGA2 might therefore be an interesting therapeutic target to overcome resistance to gemcitabine.
Cancers (2023) 15:628 (doi:10.3390/cancers15030628)