La keratina 17 localizzata nel mitocondrio promuove la chemioresistenza nel cancro pancreatico a tipo basale.

UNLABELLED: The basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) is highly lethal and therapy resistant. A better understanding of the underlying molecular mechanisms driving this aggressive tumor subtype is necessary for the development of effective therapies. Notably, upregulation of keratin 17 (K17) in cancer is associated with poor patient outcome and the basal-like PDAC subtype. In this study, we identified a critical dependency of basal-like PDACs on de novo pyrimidine biosynthesis, driven by intramitochondrial K17. Mechanistically, K17 translocated into the mitochondrial intermembrane space via a mitochondrial localization signal recognized by the translocase of