Lipid Droplets: A Key Cellular Organelle Associated with Cancer Cell Survival under Normoxia and Hypoxia

Abstract

The Warburg effect describes the phenomenon by which cancer cells obtain energy from glycolysis even under normoxic (O2-sufficient) conditions. Tumor tissues are generally exposed to hypoxia owing to inefficient and aberrant vasculature. Cancer cells have multiple molecular mechanisms to adapt to such stress conditions by reprogramming the cellular metabolism. Hypoxia-inducible factors are major transcription factors induced in cancer cells in response to hypoxia that contribute to the metabolic changes. In addition, cancer cells within hypoxic tumor areas have reduced access to serum components such as nutrients and lipids. However, the effect of such serum factor deprivation on cancer cell biology in the context of tumor hypoxia is not fully understood. Cancer cells are lipid-rich under normoxia and hypoxia, leading to the increased generation of a cellular organelle, the lipid droplet (LD). In recent years, the LD-mediated stress response mechanisms of cancer cells have been revealed. This review focuses on the production and functions of LDs in various types of cancer cells in relation to the associated cellular environment factors including tissue oxygenation status and metabolic mechanisms. This information will contribute to the current understanding of how cancer cells adapt to diverse tumor environments to promote their survival.

MGF E peptide improves anterior cruciate ligament repair by inhibiting hypoxia‐induced cell apoptosis and accelerating angiogenesis

“…Hypoxic environmental condition will occur after tissue injury due to the vessel rupture and oxygen depletion (Cramer et al, ), initiating a complex signaling cascade to direct critical responses to regulate cell survival or trigger tissue repair (Hawno et al, ; Koizume & Miyagi, ). In the current study, ACL fibroblasts were pretreated with MGF and followed subjected to hypoxic environmental conditions.…”

Lipid droplet functions beyond energy storage

“…LDs increase in abundance in many diseases involving disrupted or rewired lipid metabolism, including non-alcoholic fatty liver disease and cancer [11, 83-86]. In murine hepatocytes, the FA composition and degree of saturation in the triglyceride fraction of purified LDs are both very sensitive to nutritional and genetic perturbations [24, 87, 88].…”

“…Oxidative stress is associated with the accumulation of LDs in pathologies such as cancer and non-alcoholic fatty liver disease [83, 105-107]. It can be initiated by many different triggers, including hypoxia, chemical pro-oxidants, mitochondrial dysfunction, and ER stress.…”

Cellular transformations in near‐infrared light‐induced apoptosis in cancer cells revealed by label‐free CARS imaging

“…Oxidative stress is often associated with the accumulation of LDs in pathologies such as cancer and non‐alcoholic fatty liver disease . Furthermore, it was shown that cancer cells may promote their survival rate by protecting themselves from lipid peroxidation‐mediated cell death through inducing de novo lipogenesis . At the same time, apoptosis is known to correlate with an increased level of cytoplasmic lipid droplet content .…”