Journal
CELL STEM CELL
Volume 17, Issue 5, Pages 585-596Publisher
CELL PRESS
DOI: 10.1016/j.stem.2015.08.019
Keywords
-
Categories
Funding
- Cancer Prevention and Research Institute of Texas
- Gabrielle's Angel Foundation for Cancer Research
- National Institutes of Health [R01CA193235]
- NIH (NCRR) [S10RR024574, NIAID AI036211, NCI P30CA125123]
- NIH Common Funds Project [U24 DK097153]
Ask authors/readers for more resources
How cancer cells adapt to metabolically adverse conditions in patients and strive to proliferate is a fundamental question in cancer biology. Here we show that AMP-activated protein kinase (AMPK), a metabolic checkpoint kinase, confers metabolic stress resistance to leukemia-initiating cells (LICs) and promotes leukemogenesis. Upon dietary restriction, MLL-AF9-induced murine acute myeloid leukemia (AML) activated AMPK and maintained leukemogenic potential. AMPK deletion significantly delayed leukemogenesis and depleted LICs by reducing the expression of glucose transporter 1 (Glut1), compromising glucose flux, and increasing oxidative stress and DNA damage. LICs were particularly dependent on AMPK to suppress oxidative stress in the hypoglycemic bone marrow environment. Strikingly, AMPK inhibition synergized with physiological metabolic stress caused by dietary restriction and profoundly suppressed leukemogenesis. Our results indicate that AMPK protects LICs from metabolic stress and that combining AMPK inhibition with physiological metabolic stress potently suppresses AML by inducing oxidative stress and DNA damage.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available