title: NDRG2 overexpression enhances glucose deprivation-mediated apoptosis in breast cancer cells via inhibition of the LKB1-AMPK pathway.
abstract: The newly identified tumor suppressor, N-myc downstream-regulated gene 2 (NDRG2), has been studied in various cancers because of its anticancer and antimetastasis effects. In this study, we examined the effect of NDRG2 expression on cell viability in MDA-MB-231 human breast cancer cells under conditions that are similar to the microenvironment of solid tumors, which include glucose deprivation. NDRG2 overexpression enhanced the pro-apoptotic effects of glucose deprivation. Glucose deprivation also induced the activation of AMP-activated protein kinase (AMPK), which plays a role in protecting tumor cells from metabolic stresses. NDRG2 overexpression strongly reduced glucose deprivation-induced AMPK phosphorylation and increased the cleavage of poly (ADP-ribose) polymerase (PARP), which indicated the induction of apoptosis. The expression of a constitutively active form of AMPK effectively blocked glucose deprivation-induced apoptosis in NDRG2-overexpressing MDA-MB-231 cells. Moreover, NDRG2 overexpression also enhanced the pro-apoptotic effects of 2-deoxyglucose (2-DG) or hypoxia, an inducer of metabolic stresses. Finally, we showed that LKB1 is an upstream kinase of AMPK that is involved in the inhibition of glucose deprivation-induced AMPK activity in NDRG2-overexpressing cells. Our findings collectively suggest that NDRG2 is a negative regulator of AMPK activity and functions as a sensitizer of glucose deprivation.
authors: Department of Biological Sciences and the Research Center for Women's Diseases, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Hak-Su
authors: HS
authors: Kim
authors: Department of Biological Sciences and the Research Center for Women's Diseases, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Myung-Jin
authors: MJ
authors: Kim
authors: Department of Biological Sciences and the Research Center for Women's Diseases, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Jihyun
authors: J
authors: Lim
authors: Department of Biological Sciences and the Research Center for Women's Diseases, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Young
authors: Y
authors: Yang
authors: Department of Biological Sciences and the Research Center for Women's Diseases, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Myeong-Sok
authors: MS
authors: Lee
authors: Department of Biological Sciences and the Research Center for Women's Diseases, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Jong-Seok
authors: JS
authors: Lim
keywords: AMPK; NDRG2; apoptosis; glucose deprivation