Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ACS3 is a recently identified acyl-CoA synthetase (ACS) isozyme that preferentially utilizes laurate, myristate, arachidonate, and eicosapentaenoate among saturated and unsaturated long chain fatty acids. The ACS3 purified from COS cells transfected with the ACS3 cDNA was separated by SDS-PAGE into two major forms of 79 and 80 kDa. We report here that alternative translation initiation from ACS3 mRNA gives rise to these two isoforms of ACS3. In vitro mutagenesis of the ACS3 cDNA revealed that the translation of the 80-kDa and 79-kDa isoforms started from the first and second in-frame AUGs, respectively. The two isoforms of ACS3 expressed in COS cells exhibited similar levels of ACS activities toward palmitate and myristate. Immunocytochemistry of intact COS cells transfected with various ACS3 expression vectors suggested that the two forms are localized in the extranuclear compartment, where they exhibit a reticular pattern. In rat cerebrum, the 80-kDa isoform of ACS3 was detected mainly in the microsomal fraction. Only a trace amount of the 79-kDa isoform was detected in rat cerebrum, whereas both forms were detected in rat glioma cell line KEG1 cells.
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PMID:Alternative translation initiation generates acyl-CoA synthetase 3 isoforms with heterogeneous amino termini. 927 91

The contribution of lipid metabolic pathways to malignancy is poorly understood. Expression of the fatty acyl-CoA synthetase ACSVL3 was found to be markedly elevated in clinical malignant glioma specimens but nearly undetectable in normal glia. ACSVL3 levels correlated with the malignant behavior of human glioma cell lines and glioma cells propagated as xenografts. ACSVL3 expression was induced by the activation of oncogenic receptor tyrosine kinases (RTK) c-Met and epidermal growth factor receptor. Inhibiting c-Met activation with neutralizing anti-hepatocyte growth factor monoclonal antibodies reduced ACSVL3 expression concurrent with tumor growth inhibition in vivo. ACSVL3 expression knockdown using RNA interference, which decreased long-chain fatty acid activation, inhibited anchorage-dependent and anchorage-independent glioma cell growth by approximately 70% and approximately 90%, respectively. ACSVL3-depleted cells were less tumorigenic than control cells, and subcutaneous xenografts grew approximately 60% slower than control tumors. Orthotopic xenografts produced by ACSVL3-depleted cells were 82% to 86% smaller than control xenografts. ACSVL3 knockdown disrupted Akt function as evidenced by RTK-induced transient decreases in total and phosphorylated Akt, as well as glycogen synthase kinase 3beta, via a caspase-dependent mechanism. Expressing constitutively active myr-Akt rescued cells from the anchorage-dependent and anchorage-independent growth inhibitory effects of ACSVL3 depletion. These studies show that ACSVL3 maintains oncogenic properties of malignant glioma cells via a mechanism that involves, in part, the regulation of Akt function.
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PMID:Acyl-CoA synthetase VL3 knockdown inhibits human glioma cell proliferation and tumorigenicity. 1992 Jan 85