Lipid droplets provide metabolic flexibility for cancer progression

Abstract

A hallmark of cancer cells is their remarkable ability to efficiently adapt to favorable and hostile environments. Due to a unique metabolic flexibility, tumor cells can grow even in the absence of extracellular nutrients or in stressful scenarios. To achieve this, cancer cells need large amounts of lipids to build membranes, synthesize lipid‐derived molecules, and generate metabolic energy in the absence of other nutrients. Tumor cells potentiate strategies to obtain lipids from other cells, metabolic pathways to synthesize new lipids, and mechanisms for efficient storage, mobilization, and utilization of these lipids. Lipid droplets (LDs) are the organelles that collect and supply lipids in eukaryotes and it is increasingly recognized that the accumulation of LDs is a new hallmark of cancer cells. Furthermore, an active role of LD proteins in processes underlying tumorigenesis has been proposed. Here, by focusing on three major classes of LD‐resident proteins (perilipins, lipases, and acyl‐CoA synthetases), we provide an overview of the contribution of LDs to cancer progression and discuss the role of LD proteins during the proliferation, invasion, metastasis, apoptosis, and stemness of cancer cells.

Surface tension-driven sorting of human perilipins on lipid droplets

“…Mutations in PLIN1 and PLIN4 in particular have been linked to many metabolic phenotypes, and loss of function heterozygous mutations in PLIN1 and PLIN4 positively and negatively, respectively, correlate with metabolic disease (14, 60). Over-expression of PLIN2 and PLIN3 has been observed in a number of cancers and often correlates with higher proliferation and poor prognosis (61). Overexpression of PLIN4 has been shown to promote drug resistance of triple-negative breast cancer (62).…”