Lipid droplets: platforms with multiple functions in cancer hallmarks

Abstract

Lipid droplets (also known as lipid bodies) are lipid-rich, cytoplasmic organelles that play important roles in cell signaling, lipid metabolism, membrane trafficking, and the production of inflammatory mediators. Lipid droplet biogenesis is a regulated process, and accumulation of these organelles within leukocytes, epithelial cells, hepatocytes, and other nonadipocyte cells is a frequently observed phenotype in several physiologic or pathogenic situations and is thoroughly described during inflammatory conditions. Moreover, in recent years, several studies have described an increase in intracellular lipid accumulation in different neoplastic processes, although it is not clear whether lipid droplet accumulation is directly involved in the establishment of these different types of malignancies. This review discusses current evidence related to the biogenesis, composition and functions of lipid droplets related to the hallmarks of cancer: inflammation, cell metabolism, increased proliferation, escape from cell death, and hypoxia. Moreover, the potential of lipid droplets as markers of disease and targets for novel anti-inflammatory and antineoplastic therapies will be discussed.

Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells

“…Since GRP78 is a marker of endoplasmic reticulum stress and was significantly increased after the treatment with C6 ( Figure 9 b), this could be an indication that C6 induced endoplasmic reticulum stress-mediated autophagy ( Figure 9 a,b). Furthermore, the initiation of autophagy is commonly associated with lipid droplet inclusion into autophagosomes and subsequent degradation by lysosomes (lipophagy) [ 54 , 55 ]; however, in this study an accumulation of lipid droplets was observed. The small guanosine triphosphatase Rab7 is indispensable for lipophagy [ 56 ] and is associated with lipid droplets and lysosomes under starvation conditions [ 57 ].…”

Immunohistochemical staining reveals differential expression of ACSL3 and ACSL4 in hepatocellular carcinoma and hepatic gastrointestinal metastases

“…In such instances, ACSL3/4 overexpression and lipid droplet association may represent an adaptive response. However, it is important to note that while there is substantial evidence that increased intracellular lipid storage can define a more aggressive class of cancers (reviewed in [85,86]), the association of both enzymes with lipid droplets in HCC cells does not necessarily imply that this forms part of an oncogenic process.…”

Falcarindiol Purified From Carrots Leads to Elevated Levels of Lipid Droplets and Upregulation of Peroxisome Proliferator-Activated Receptor-γ Gene Expression in Cellular Models

“…Accumulation of excess cholesterol in the form of cholesteryl esters is another characteristic of cancer cells. The cholesteryl esters are usually stored in lipid droplets (LD) serving as a readily available reservoir for neutral lipids ( Tirinato et al, 2017 ; Cruz et al, 2020 ). Although an accumulation of lipid droplets in cancer cells can lead to increased proliferation and aggressiveness of tumors ( Gu et al, 2019 ; Cruz et al, 2020 ), it appears to depend on the total amount of cholesterol accumulated in cancer cells.…”

“…The cholesteryl esters are usually stored in lipid droplets (LD) serving as a readily available reservoir for neutral lipids ( Tirinato et al, 2017 ; Cruz et al, 2020 ). Although an accumulation of lipid droplets in cancer cells can lead to increased proliferation and aggressiveness of tumors ( Gu et al, 2019 ; Cruz et al, 2020 ), it appears to depend on the total amount of cholesterol accumulated in cancer cells. It has for example been shown that some polyunsaturated fatty acids, such as docosahexaenoic acid, cause a redistribution of cholesterol from intracellular compartments (mitochondria and ER) to polyunsaturated-enriched lipid droplets but not in an increase of total cholesterol ( Jakobsen et al, 2008 ).…”