MK2 Regulates Ras Oncogenesis through Stimulating ROS Production. Genes Cancer 2012 Jul;3(7-8):521-30
Date
12/25/2012Pubmed ID
23264852Pubmed Central ID
PMC3527985DOI
10.1177/1947601912462718Scopus ID
2-s2.0-84875498622 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
Ras signals through both mitogenic and stress pathways and studies of Ras regulatory effects of stress pathways hold great promise to control Ras-dependent malignancies. Our previous work showed Ras activation of a stress kinase (MAPK-activated protein kinase 2 [MK2]), and here, we examine regulatory effects of MK2 on Ras oncogenesis. MK2 knockout was shown to increase Ras transformation in mouse embryonic fibroblasts (MEFs) in vitro and to enhance the resultant tumor growth in mice, indicating a tumor suppressor activity. In Ras-dependent and -independent human colon cancer, however, MK2-forced expression increases and MK2 depletion decreases the malignant growth, suggesting its oncogenic activity. The oncogenic activity of MK2 couples with its activation by both stress and mitogenic signals through extracellular signal-regulated kinase and p38α pathways, whereas its tumor-suppressing effect links to its stimulation only by stress downstream of p38α. Of interest, MK2 was shown to decrease intracellular levels of reactive oxygen species (ROS) in MEFs but increase its production in human colon cancer cells, and experiments with antioxidants revealed that ROS is required for Ras oncogenesis in both systems. These results indicate that MK2 can increase or decrease Ras oncogenesis dependent of its ROS regulatory activities.
Author List
Kobayashi Y, Qi X, Chen GAuthors
Guan Chen MD, PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinXiao-Mei Qi MD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
