Abstract
Cancer cells possess remarkable abilities to adapt to adverse environmental conditions. Their survival during severe nutrient and oxidative stress depends on their capacity to acquire extracellular lipids and the plasticity of their mechanisms for intracellular lipid synthesis, mobilisation, and recycling. Lipid droplets, cytosolic fat storage organelles present in most cells from yeast to men, are emerging as major regulators of lipid metabolism, trafficking, and signalling in various cells and tissues exposed to stress. Their biogenesis is induced by nutrient and oxidative stress and they accumulate in various cancers. Lipid droplets act as switches that coordinate lipid trafficking and consumption for different purposes in the cell, such as energy production, protection against oxidative stress or membrane biogenesis during rapid cell growth. They sequester toxic lipids, such as fatty acids, cholesterol and ceramides, thereby preventing lipotoxic cell damage and engage in a complex relationship with autophagy. Here, we focus on the emerging mechanisms of stress-induced lipid droplet biogenesis; their roles during nutrient, lipotoxic, and oxidative stress; and the relationship between lipid droplets and autophagy. The recently discovered principles of lipid droplet biology can improve our understanding of the mechanisms that govern cancer cell adaptability and resilience to stress.
Highlights
Cancer cells are often faced with an inconsistent and limited availability of nutrients due to poor vascularization [1]
Inhibition of mTORc1 in the presence of nutrients led to activation of autophagy and was sufficient to induce lipid droplet biogenesis, suggesting that autophagy-derived lipid droplet synthesis is not limited to starvation, but it may be important for various conditions characterized by high autophagic flux, including cancer [31]
Lipid droplets have long been regarded as inert fat storage depots and we know very little about their lipid and protein composition, dynamics, and functions in the cell
Summary
Cancer cells are often faced with an inconsistent and limited availability of nutrients due to poor vascularization [1]. The breakdown of lipid droplets provides FAs and other lipids that act as signalling molecules by themselves—e.g., by interacting with transcription factors such as peroxisome proliferator-activated receptors (PPARs) and sterol-regulatory element binding proteins (SREBPs)—or they are converted into bioactive lipid mediators, such as eicosanoids, that act as paracrine and autocrine messengers affecting inflammatory signalling, metabolism, proliferation, migration, and metastasis [14,63,64,65,66] This emerging aspect of lipid droplet biology will not be covered in this review, but we would like to refer the reader to several excellent recent reviews [13,18,67,68,69]. Many of these recently discovered principles of lipid droplet biology can improve our understanding of the mechanisms that govern cancer cell resistance to stress
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