Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 70, Issue 12, Pages 2175-2190Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-012-1249-1
Keywords
NAD(H); Cancer metabolism; Migration; Invasion; Lactic acid
Categories
Funding
- Dutch Cancer Society [KUN-2005-3333]
- Deutsche Forschungsgemeinschaft [Sto 654/3-2]
- EMBO Short Term Fellowship
- Vanderes Foundation [225]
- Italian Association for Cancer Research (AIRC)
- European Union [237946]
Ask authors/readers for more resources
Oncogenic transformation involves reprogramming of cell metabolism, whereby steady-state levels of intracellular NAD(+) and NADH can undergo dramatic changes while ATP concentration is generally well maintained. Altered expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD(+)-salvage, accompanies the changes in NAD(H) during tumorigenesis. Here, we show by genetic and pharmacological inhibition of NAMPT in glioma cells that fluctuation in intracellular [NAD(H)] differentially affects cell growth and morphodynamics, with motility/invasion capacity showing the highest sensitivity to [NAD(H)] decrease. Extracellular supplementation of NAD(+) or re-expression of NAMPT abolished the effects. The effects of NAD(H) decrease on cell motility appeared parallel coupled with diminished pyruvate-lactate conversion by lactate dehydrogenase (LDH) and with changes in intracellular and extracellular pH. The addition of lactic acid rescued and knockdown of LDH-A replicated the effects of [NAD(H)] on motility. Combined, our observations demonstrate that [NAD(H)] is an important metabolic component of cancer cell motility. Nutrient or drug-mediated modulation of NAD(H) levels may therefore represent a new option for blocking the invasive behavior of tumors.
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