Unexpected gain of function for the scaffolding protein plectin due to mislocalization in pancreatic cancer
Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes par lesquels la plectine, normalement une protéine de structure intracellulaire, favorise le développement d'un adénocarcinome canalaire du pancréas lorsqu'elle est présente sur la surface extracellulaire des cellules cancéreuses
We recently demonstrated that plectin is a robust biomarker for pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive malignancies. In normal physiology, plectin is an intracellular scaffolding protein, but we have demonstrated localization on the extracellular surface of PDAC cells. In this study, we confirmed cell surface localization. Interestingly, we found that plectin cell surface localization was attributable to its presence in exosomes secreted from PDAC cells, which is dependent on the expression of integrin β4, a protein known to interact with cytosolic plectin. Moreover, plectin expression was necessary for efficient exosome production and was required to sustain enhanced tumor growth in immunodeficient and in immunocompetent mice. It is now clear that this PDAC biomarker plays a role in PDAC, and further understanding of plectin’s contribution to PDAC could enable improved therapies.