Fatty Acids and Breast Cancer: Make Them on Site or Have Them Delivered

Abstract

Brisk fatty acid (FA) production by cancer cells is accommodated by the Warburg effect. Most breast and other cancer cell types are addicted to fatty acids (FA), which they require for membrane phospholipid synthesis, signaling purposes, and energy production. Expression of the enzymes required for FA synthesis is closely linked to each of the major classes of signaling molecules that stimulate BC cell proliferation. This review focuses on the regulation of FA synthesis in BC cells, and the impact of FA, or the lack thereof, on the tumor cell phenotype. Given growing awareness of the impact of dietary fat and obesity on BC biology, we will also examine the less-frequently considered notion that, in addition to de novo FA synthesis, the lipolytic uptake of preformed FA may also be an important mechanism of lipid acquisition. Indeed, it appears that cancer cells may exist at different points along a “lipogenic-lipolytic axis”, and FA uptake could thwart attempts to exploit the strict requirement for FA focused solely on inhibition of de novo FA synthesis. Strategies for clinically targeting FA metabolism will be discussed, and the current status of the medicinal chemistry in this area will be assessed.

Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate‐induced apoptosis

“…This study has focused on the contribution of FA metabolism in mediating palmitate-induced apoptosis. Extensive literature exists describing the effects of FAs on BrCa cell proliferation and migration/invasion (see review (Kinlaw et al, 2016)). For example, oleate increases proliferation, migration and invasion in MDA-MB-231 cells (Hardy et al, 2005;Wu et al, 2017) and MCF-7 cells (Soto-Guzman et al, 2008), but this effect on MCF-7 cells is not always observed (Hardy et al, 2005).…”

Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors

“…In condition of caloric excess, fatty acid uptake and synthesis in cells would mimic the endogenous synthesis of fatty acids in tumors, and this has been shown to interfere with the cancer therapeutic effects of fatty acid synthase inhibitors [52]. In our recent clinical trial of omega-3 fatty acid supplementation, obese versus normal weight individuals exhibited smaller decreases in colonic PGE 2 concentrations post supplementation [53].…”

Aberrant Phosphorylation of SMAD4 Thr277-Mediated USP9x–SMAD4 Interaction by Free Fatty Acids Promotes Breast Cancer Metastasis

“…Overweight/obesity and HFD in both humans and rodents is characterized by elevated free tatty acids (FFA) levels (10,11). Increasing evidence points to FFA signaling playing an important role in tumorigenesis and BC development and progression.…”