Epigenetic silencing of diacylglycerol kinase gamma in colorectal cancer

• DOI: 10.1002/mc.22631
• Publication Date: 2017-02-20T12:53:41Z
• Authors: Masahiro Kai; Eiichiro Yamamoto; Akiko Sato; Hiro‐o Yamano; Takeshi Niinuma; Hiroshi Kitajima; Taku Harada; Hironori Aoki; Reo Maruyama; Mutsumi Toyota; Tomo Hatahira; Hiroshi Nakase; Tamotsu Sugai; Toshiharu Yamashita; Minoru Toyota; Hiromu Suzuki
• Keywords: Ectopic expression; Demethylating agent

Diacylglycerol kinases (DGKs) are important regulators of cell signaling and have been implicated in human malignancies. Whether epigenetic alterations involved the dysregulation DGKs cancer is unknown, however. We therefore analyzed methylation promoter CpG islands DGK genes colorectal (CRC) lines. found that DGKG , which encodes DGKγ, was hypermethylated all CRC lines tested ( n = 9), but not methylated normal colonic tissue. Correspondingly, expression suppressed tissue, restored cells by treatment with DNA methyltransferase inhibitor 5‐aza‐2′‐deoxycytidine (5‐aza‐dC). frequently observed primary CRCs (73/141, 51.8%) positively associated KRAS BRAF mutations island methylator phenotype (CIMP). also detected adenomas (89 177, 50.3%), suggests it an early event during tumorigenesis. Ectopic wild‐type DGKγ did suppress proliferation, migration invasion. Notably, both constitutively active kinase‐dead mutants exerted inhibitory effects on invasion, mutant forms Rac1 activity cells. These data suggest may play a tumor suppressor role CRC.