Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer.

Genes Dev 2016 Apr 17;30(7):772-85. Epub 2016 Mar 17.

Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;

Pancreatic ductal adenocarcinoma (PDAC) is a lethal form of cancer with few therapeutic options. We found that levels of the lysine methyltransferase SMYD2 (SET and MYND domain 2) are elevated in PDAC and that genetic and pharmacological inhibition of SMYD2 restricts PDAC growth. We further identified the stress response kinase MAPKAPK3 (MK3) as a new physiologic substrate of SMYD2 in PDAC cells. 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. These findings uncover a pivotal role for SMYD2 in promoting pancreatic cancer.

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http://dx.doi.org/10.1101/gad.275529.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826394PMC
April 2016
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References

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What goes up must come down: molecular basis of MAPKAP kinase 2/3-dependent regulation of the inflammatory response and its inhibition
Biol Chem 2013

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