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Lysine methylation signaling in pancreatic cancer

Roth, Gaël, S.a,b,c; Casanova, Alexandre, G.a; Lemonnier, Nathanaëla; Reynoird, Nicolasa

doi: 10.1097/CCO.0000000000000421
CANCER BIOLOGY: Edited by Pierre Hainaut

Purpose of review Despite better knowledge of its genetic basis, pancreatic cancer is still highly lethal with very few therapeutic options. In this review, we discuss the potential impact of epigenetic therapies, focusing on lysine methylation signaling and its implication in pancreatic cancer.

Recent findings Protein lysine methylation, a key mechanism of posttranslational modifications of histone proteins, has emerged as a major cell signaling mechanism regulating physiologic and pathologic processes including cancer. This finely tuned and dynamic signaling mechanism is regulated by lysine methyltransferases (KMT), lysine demethylases (KDM) and signal transducers harboring methyl-binding domains. Recent evidence demonstrates that overexpression of cytoplasmic KMT and resulting enhanced lysine methylation is a reversible event that enhances oncogenic signaling through the Ras and Mitogen-Activated Protein Kinases pathway in pancreatic cancer, opening perspectives for new anticancer chemotherapeutics aimed at controlling these activities.

Summary The development of potent and specific inhibitors of lysine methylation signaling may represent a hitherto largely unexplored avenue for new forms of targeted therapy in cancer, with great potential for yet hard-to-treat cancers such as pancreatic cancer.

aInstitute for Advanced Biosciences, ‘Molecular Pathologies of Cancer and Biomarkers’ Lab, INSERM U1209 – CNRS UMR5309, Université Grenoble Alpes

bClinique Universitaire d’Hépato-Gastroentérologie, Pôle Digidune, CHU Grenoble-Alpes

cFaculté de médecine, Université Grenoble Alpes, Grenoble, France

Correspondence to Nicolas Reynoird, Institute for Advanced Biosciences, ‘Molecular Pathologies of Cancer and Biomarkers’ Lab, CNRS UMR5309 – INSERM U1209 – Grenoble Alpes University, Site santé, allée des Alpes, 38700 la Tronche, France. Tel: +33 4 76 54 95 76; e-mail: Nicolas.reynoird@univ-grenoble-alpes.fr

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