title: [Autophagy contributes to the initiation of pancreatic cancer].
abstract: The pancreatic adenocarcinoma initiation results from the interaction of genetic events combined with multiple other factors. Among the genetic alterations that contribute to the pathogenesis of this disease, the mutation of the KRAS oncogene is required but not sufficient to trigger this cancer. Pancreatitis, an inflammatory disease, facilitates and accelerates the transformation of pancreatic cells when the KRAS oncogene is mutated. Of note, the repertoire of molecular mediators of pancreatitis which are responsible of the promotion of KRAS-mediated transformation is not completely defined. Importantly, autophagy has been proposed as one of the cellular mechanisms contributing to pancreatic carcinogenesis, especially in the initial phases, in which the oncogene KRAS appears to play its leading role. In addition, autophagy is strongly induced during pancreatitis. Although some aspects of autophagy in pancreatic cancer development are not completely established, we can affirm that overexpression of VMP1, an inducer of autophagy which is specifically activated in pancreas during pancreatitis, improves the development of pancreatic precancerous lesions PanINs when the oncogene KRAS is mutated. In addition, inhibition of the autophagic flux with chloroquine inhibits the KRAS pro-tumor effect in the pancreas. In conclusion, activation of expression of VMP1 improves the pro-tumor role of KRAS in pancreas.
authors.affiliation: Centre de recherche en cancérologie de Marseille (CRCM), Inserm U1068, CNRS UMR 7258, Aix-Marseille Université et Institut Paoli-Calmettes, Parc scientifique et technologique de Luminy, 163, avenue de Luminy, 13288 Marseille, France.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Iovanna
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000473:pathology*; D015398:Signal Transduction