Lipid droplets, potential biomarker and metabolic target in glioblastoma

Abstract

Lipid droplets (LDs) are subcellular organelles that store large amounts of the neutral lipids, triglycerides (TG) and/or cholesteryl esters (CE). LDs are commonly formed in adipocytes, liver cells and macrophages, and their formation has been shown to be associated with the progression of metabolic diseases, i.e., obesity, fatty liver and atherosclerosis. Interestingly, LDs are also found in some tumor tissues. We recently showed that LDs are prevalent in glioblastoma (GBM), the most deadly brain tumor, but are not detectable in low-grade gliomas and normal brain tissues, suggesting that LDs may serve as a novel diagnostic biomarker for GBM. This short review will briefly introduce LD biology, summarize recent observations about LDs in several types of cancer tissues, and discuss LD formation in GBM. Moreover, we will highlight the role of SOAT1 (sterol-O transferase 1), a key enzyme regulating CE synthesis and LD formation in GBM, in the regulation of SREBP (sterol regulatory-element binding protein) activation. The therapeutic potential of LDs and SOAT1 will be discussed.

Genome-Scale Metabolic Modeling of Glioblastoma Reveals Promising Targets for Drug Development

“…Evidently, three of the remaining four essential genes have a clear role in lipid metabolism, e.g., cardiolipin synthesis and carnitine transport. Elevated lipid levels and reprogramming of lipid metabolism have previously been reported for GBM and findings related to lipid metabolism are therefore to be expected (Geng and Guo, 2017). One of the three genes is SLC22A5, a membrane protein responsible for the cellular uptake of carnitine (UniProt Consortium, 2018).…”

Alterations of Lipid Metabolism in Cancer: Implications in Prognosis and Treatment

“…LDs itself have been proposed as novel diagnostic biomarkers for glioblastoma. It has been demonstrated that while they are not detectable in low-grade gliomas or normal brain tissues, they are common in glioblastoma, the most lethal brain tumor (70). Among the LD-associated proteins, there are enzymes of the sterol biosynthetic pathway, the acyl-CoA metabolism (ACSLs), and triacylglycerol (TAG) biosynthesis.…”

Assessment of acyl-CoA cholesterol acyltransferase (ACAT-1) role in ovarian cancer progression—An in vitro study

“…Excessive lipids and cholesterol in cancer cells are converted to triglycerides and cholesteryl esters (CE) for storage in lipid droplets (LDs). Several reports indicate increased amount of lipid droplets in various types of tumors including leukemia, glioblastoma, renal clear cell carcinoma, and cancers of the prostate, colon, breast and pancreas [10][11][12][13][14][15][16]. As observed in these cancers, CE were shown to be the major component of LDs within cancerous tissue as compared to normal tissue [17].…”

“…Whereas ACAT-2 is associated with lipoprotein particle secretion, ACAT-1 is ubiquitous and known to maintain cellular cholesterol homeostasis. ACAT-1 mediated accumulation of CE was shown to positively correlate with poor survival in pancreatic and prostate cancers [12,13,[22][23][24][25][26][27]. While the role of ACAT-1/CE accumulation is being studied in various cancers, information regarding the contribution of these mediators in ovarian cancer is relatively scarce.…”