Abstract A44: Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is a lethal form of cancer with few therapeutic options. We find that levels of the lysine methyltransferase SMYD2 are elevated in precancerous lesions and PDAC and that SMYD2 normally promotes Ras-driven development of PDAC. Notably, loss of SMYD2 correlates with diminished inflammation in PDAC and we identify the stress-response kinase MAPKAPK3 as a new and physiologically relevant SMYD2 substrate. Inhibition of MAPKAPK3 impedes PDAC growth, identifying a potential new kinase target in PDAC. Finally, we show that inhibition of SMYD2 cooperates with standard chemotherapy to treat PDAC cells and tumors. Together, our findings suggest new roles for SMYD2 in inflammation and stress responses, and identify SMYD2 and MAPKAPK3 as potential therapeutic targets to treat pancreatic cancer. Citation Format: Pawel K. Mazur, Nicolas Reynoird, Timo Stellfeld, Natasha M. Flores, Shane M. Lofgren, Scott M. Carlson, Elisabeth Brambilla, Pierre Hainaut, Ewa B. Kaznowska, Cheryl H. Arrowsmith, Purvesh Khatri, Carlo Stresemann, Or Gozani, Julien Sage.{Authors}. Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A44.