Abstract B33: Assessing the role of DGAT activity on lipid homeostasis and cancer cell survival

Studies on the effects of modulating the lipid composition of cells have found that increases in saturated fatty acid levels can lead to ER stress, activation of the unfolded protein response (UPR) and cell death. These effects may occur through saturation of the phospholipid pool and subsequent deterioration of ER membrane function. Changes in the composition of the ER membrane can be sensed by the two UPR stress sensors IRE1 and PERK and lead to activation of UPR targets.Rapidly proliferating cancer cells frequently exhibit elevated ER stress due to their increased protein translation rate. In addition, the tumor microenvironment is frequently hypoxic and a lack of oxygen can inhibit the activity of the fatty acid desaturase SCD1. This leads to saturation of the fatty acid pool and renders the ER less able to cope with high levels of protein synthesis, making the maintenance of adequate lipid homeostasis of paramount importance to cancer cells within hypoxic tumor domains. Tumor cells adapt to these conditions through a variety of mechanisms, including the uptake of exogenous unsaturated lipid. Both hypoxia and the presence of certain oncogenic drivers have been found to increase lipid uptake, which was found to protect cancer cells against inhibition of SCD1.Since fatty acids can be converted to triglycerides and stored within lipid droplets, we asked whether cancer cells also cope with saturation of their fatty acid pool by storing excess saturated fatty acids as triglyce...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways and Cancer Metabolism: Poster Presentations - Proffered Abstracts Source Type: research