The membrane protein sortilin can be targeted to inhibit pancreatic cancer cell invasion
Menée à l'aide de lignées cellulaires et de tissus pancréatiques normaux ou cancéreux, cette étude met en évidence l'intérêt de cibler la sortiline, une protéine membranaire, pour inhiber le processus invasif des cellules cancéreuses
Pancreatic cancer has a dismal prognosis and there is no targeted therapy against this malignancy. The neuronal membrane protein sortilin is emerging as a regulator of cancer cell development, but its expression and impact in pancreatic cancer is unknown. In this study, we found that sortilin expression was higher in pancreatic cell lines vs normal pancreatic ductal epithelial cells, as demonstrated by Western blot and mass spectrometry. The increased sortilin level in pancreatic cancer cells was confirmed by immunohistochemistry in a series of 99 human pancreatic adenocarcinomas vs 48 normal pancreatic tissues (p=0.0014). Sortilin inhibition by siRNA and the pharmacological inhibitor AF38469 strongly reduced the adhesion and invasion of pancreatic cancer cells without affecting cell survival and viability. Sortilin inhibition also decreased the phosphorylation of the focal adhesion kinase (FAK) in Tyr925. Together, these data reveal that sortilin contributes to pancreatic cancer invasion and could eventually be targeted in therapy.