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Phospholipase D activates HIF-1-VEGF pathway via phosphatidic acid
- Source :
- Experimental and Molecular Medicine; December 2014, Vol. 46 Issue: 12 pe126-e126, 1p
- Publication Year :
- 2014
-
Abstract
- Growth factor-stimulated phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine (PC), generating phosphatidic acid (PA) which may act as a second messenger during cell proliferation and survival. Therefore, PLD is believed to play an important role in tumorigenesis. In this study, a potential mechanism for PLD-mediated tumorigenesis was explored. Ectopic expression of PLD1 or PLD2 in human glioma U87 cells increased the expression of hypoxia-inducible factor-1a (HIF-1a) protein. PLD-induced HIF-1 activation led to the secretion of vascular endothelial growth factor (VEGF), a HIF-1 target gene involved in tumorigenesis. PLD induction of HIF-1a was significantly attenuated by 1-butanol which blocks PA production by PLD, and PA per se was able to elevate HIF-1a protein level. Inhibition of mTOR, a PA-responsive kinase, reduced the levels of HIF-1a and VEGF in PLD-overexpressed cells. Epidermal growth factor activated PLD and increased the levels of HIF-1a and VEGF in U87 cells. A specific PLD inhibitor abolished expression of HIF-1a and secretion of VEGF. PLD may utilize HIF-1-VEGF pathway for PLD-mediated tumor cell proliferation and survival.
Details
- Language :
- English
- ISSN :
- 12263613 and 20926413
- Volume :
- 46
- Issue :
- 12
- Database :
- Supplemental Index
- Journal :
- Experimental and Molecular Medicine
- Publication Type :
- Periodical
- Accession number :
- ejs41070068
- Full Text :
- https://doi.org/10.1038/emm.2014.86