Emergence of Lipid Droplets in the Mechanisms of Carcinogenesis and Therapeutic Responses

SIMPLE SUMMARY: Cancer cells are characterized by an increased energy metabolism, to cope with a high rate of proliferation. Recently, alterations in lipid metabolism have been recognized to be involved in tumor progression. Lipid droplets represent dynamic entities implied in such a phenomenon. This review aims to point out the metabolic pathways that are presumed to be engaged in cancer cell survival and growth in order to define potential biomarkers of tumor progression and new therapeutic strategies in the treatment of cancer. ABSTRACT: Cancer shares common risk factors with cardiovascular diseases such as dyslipidemia, obesity and inflammation. In both cases, dysregulations of lipid metabolism occur, and lipid vesicles emerge as important factors that can influence carcinogenesis. In this review, the role of different lipids known to be involved in cancer and its response to treatments is detailed. In particular, lipid droplets (LDs), initially described for their role in lipid storage, exert multiple functions, from the physiological prevention of LD coalescence and regulation of endoplasmic reticulum homeostasis to pathological involvement in tumor progression and aggressiveness. Analysis of LDs highlights the importance of phosphatidylcholine metabolism and the diversity of lipid synthesis enzymes. In many cancers, the phosphatidylcholine pathways are disrupted, modifying the expression of genes coding for metabolic enzymes. Tumor microenvironment conditions, such as hypoxia, different types of stress or inflammatory conditions, are also important determinants of LD behavior in cancer cells. Therefore, LDs represent therapeutic targets in cancer, and many lipid mediators have emerged as potential biomarkers for cancer onset, progression, and/or resistance.