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| Content Provider | Springer Nature Link |
|---|---|
| Author | Horssen, Remco Willemse, Marieke Haeger, Anna Attanasio, Francesca Güneri, Tuba Schwab, Albrecht Stock, Christian M. Buccione, Roberto Fransen, Jack A. M. Wieringa, Bé |
| Copyright Year | 2013 |
| Abstract | 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. |
| Starting Page | 2175 |
| Ending Page | 2190 |
| Page Count | 16 |
| File Format | |
| ISSN | 1420682X |
| Journal | Cellular and Molecular Life Sciences |
| Volume Number | 70 |
| Issue Number | 12 |
| e-ISSN | 14209071 |
| Language | English |
| Publisher | SP Birkhäuser Verlag Basel |
| Publisher Date | 2013-01-10 |
| Publisher Place | Basel |
| Access Restriction | Subscribed |
| Subject Keyword | NAD(H) Cancer metabolism Migration Invasion Lactic acid Cell Biology Biomedicine general Life Sciences Biochemistry |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology Molecular Medicine Pharmacology Cellular and Molecular Neuroscience |
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