Elevated expression of fatty acid synthase and nuclear localization of carnitine palmitoyltransferase 1C are common among human gliomas

Abstract

Fatty acid synthase (FASN) and carnitine palmitoyltransferase 1C (CPT1C), a brain-specific isoform of the CPT1 family, are upregulated in certain types of cancers, including gliomas. Acetyl-CoA carboxylase (ACC) catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis, and its phosphorylated form inhibits lipid synthesis. We examined the expression and subcellular localization of these fatty acid metabolism-related molecules in human gliomas. We performed immunostaining of two glioma cell lines (U373MG and U87MG) and 41 surgical specimens of diffuse gliomas with various histological grades (21 with the isocitrate dehydrogenase 1(IDH1) R132H mutation and 20 without the mutation). In the cultured glioma cells, CPT1C and phosphorylated ACC (p-ACC) were mainly localized to the nuclei, whereas FASN localized to the cytoplasm. In the surgical specimens, most glioma tissues showed nuclear staining for CPT1C and p-ACC, and cytoplasmic staining for FASN, regardless of the genetic status of IDH1 and the histological grade. Therefore, elevated cytoplasmic expression of FASN and nuclear localization of CPT1C are common among human diffuse gliomas, which may be regulated by the differential phosphorylation status of ACC in the cellular compartment.

AMPAR interacting protein CPT1C enhances surface expression of GluA1-containing receptors

“…Therefore, it is suggested that CPT1C promotes cancer cell survival and tumor growth and it has been proposed as a new therapeutic target in cancer treatment. It is noteworthy that recent studies report an aberrant expression of CPT1C in gliomas (Cirillo et al, 2014 ; Wakamiya et al, 2014 ). These findings highlight the importance of unraveling the molecular mechanisms of CPT1C, which could be of great interest across a range of fields, for example in the study of new anticancer therapies and new diagnostic or prognostic markers.…”

Comparison of three 18F-labeled carboxylic acids with 18F-FDG of the differentiation tumor from inflammation in model mice

“…For 18 F-FPA, the ratio of tumor-to-inflammation was lower than that of 18 F-FDG (Table 1 ), but the higher selectivity indices of tumor-to-inflammation (muscle or blood corrected ratios of tumor-to-inflammation, 3.52 ± 0.13 or 8.00 ± 1.37) were observed. The significant uptake of 18 F-FAC and 18 F-FPA in the inflammatory lesions might be attributed to the high expression of the acetyl- or propionyl-CoA synthetases and fatty acid synthnase in these tissues [ 34 – 36 ]. In addition, the higher uptake of 18 F-FAC and 18 F-FPA were observed in the lower part of the gut, which was a result of the re-absorption of small carboxylic acids occurrence [ 37 ].…”

Carnitine palmitoyltransferase 1C: From cognition to cancer

“…The fact that CPT1C is involved in ceramide metabolism in normal neuronal cells [47] and that CPT1C deficiency in embryonic stem cells causes the accumulation of specific species of longchain FAs, among them arachidonic acid [31], suggest that CPT1C affects additional, as yet undefined, pathways. Moreover, recent studies performed by Wakamiya et al [125] showed that a truncated form of CPT1C is located in the nuclei of diffuse gliomas of…”