Lipid droplets as metabolic determinants for stemness and chemoresistance in cancer

Abstract

Previously regarded as simple fat storage particles, new evidence suggests that lipid droplets (LDs) are dynamic and functional organelles involved in key cellular processes such as membrane biosynthesis, lipid metabolism, cell signalling and inflammation. Indeed, an increased LD content is one of the most apparent features resulting from lipid metabolism reprogramming necessary to support the basic functions of cancer cells. LDs have been associated to different cellular processes involved in cancer progression and aggressiveness, such as tumorigenicity, invasion and metastasis, as well as chemoresistance. Interestingly, all of these processes are controlled by a subpopulation of highly aggressive tumoral cells named cancer stem cells (CSCs), suggesting that LDs may be fundamental elements for stemness in cancer. Considering the key role of CSCs on chemoresistance and disease relapse, main factors of therapy failure, the design of novel therapeutic approaches targeting these cells may be the only chance for long-term survival in cancer patients. In this sense, their biology and functional properties render LDs excellent candidates for target discovery and design of combined therapeutic strategies. In this review, we summarise the current knowledge identifying LDs and CSCs as main contributors to cancer aggressiveness, metastasis and chemoresistance.

Keywords: Lipids, Lipid droplets, Lipid metabolism, Stemness, Cancer stem cells, Chemoresistance

Core Tip: Increasing evidence suggests that lipid droplets (LDs) support cancer stem cells (CSCs) functionality at different levels. Indeed, an increased LD content has been linked to tumorigenicity, metastatic spread and chemoresistance in different cancer types, highlighting their value as prognostic and treatment response predictive biomarker. A deeper understanding of the molecular mechanisms by which LDs control these processes would expedite the discovery of novel potentially druggable targets and the design of more efficient therapeutic strategies aimed at eliminating highly tumorigenic CSCs.