Critical role of acylglycerol kinase in epidermal growth factor-induced mitogenesis of prostate cancer cells.
The bioactive phospholipids, LPA (lysophosphatidic acid) and PA (phosphatidic acid), regulate pivotal processes related to the pathogenesis of cancer. Recently, we cloned a novel type of lipid kinase that phosphorylates monoacylglycerols (such as 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand) and diacylglycerols, to form LPA and PA, respectively. This AGK (acylglycerol kinase) is highly expressed in prostate cancer cell lines and the results reviewed here suggest that AGK might be a critical player in the initiation and progression of prostate cancer. Intriguingly, down-regulation of endogenous AGK inhibited EGF (epidermal growth factor), but not LPA-induced ERK1/2 (extracellular-signal-regulated kinase 1/2) activation and progression through the S-phase of the cell cycle. In this review, we will summarize the evidence demonstrating that AGK amplifies EGF growth signalling pathways that play an important role in the pathophysiology of prostate cancer. Because LPA has long been implicated as an autocrine and paracrine growth stimulatory factor for prostate cancer cells, the identification of this novel lipid kinase that regulates its production could provide new and useful targets for preventive or therapeutic measures.
Spiegel
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S
Department of Biochemistry, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, VA 23298, USA. sspiegel@vcu.edu
Milstien
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S
D049109:Cell Proliferation; D002470:Cell Survival; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism; D008297:Male; D010712:Phosphatidic Acids / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D008246:Lysophospholipids; D010712:Phosphatidic Acids; D043562:Receptors, G-Protein-Coupled; D004815:Epidermal Growth Factor; D017853:Phosphotransferases (Alcohol Group Acceptor); C025944:acylglycerol kinase; C032881:lysophosphatidic acid