NDRG2 overexpression enhances glucose deprivation-mediated apoptosis in breast cancer cells via inhibition of the LKB1-AMPK pathway
- Authors
- Kim H.-S.; Kim M.-J.; Lim J.; Yang Y.; Lee M.-S.; Lim J.-S.
- Issue Date
- May-2014
- Publisher
- Impact Journals LLC
- Keywords
- AMPK; Apoptosis; Glucose deprivation; NDRG2
- Citation
- Genes and Cancer, v.5, no.5-6, pp 175 - 185
- Pages
- 11
- Journal Title
- Genes and Cancer
- Volume
- 5
- Number
- 5-6
- Start Page
- 175
- End Page
- 185
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/10899
- DOI
- 10.18632%2Fgenesandcancer.17
- ISSN
- 1947-6019
1947-6027
- 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-apoptoti ceffects 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. © 2014, Impact Journals LLC. All rights reserved.
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