Fatty acid metabolism in breast cancer subtypes

Abstract

Dysregulation of fatty acid metabolism is recognized as a component of malignant transformation in many different cancers, including breast; yet the potential for targeting this pathway for prevention and/or treatment of cancer remains unrealized. Evidence indicates that proteins involved in both synthesis and oxidation of fatty acids play a pivotal role in the proliferation, migration and invasion of breast cancer cells. The following essay summarizes data implicating specific fatty acid metabolic enzymes in the genesis and progression of breast cancer, and further categorizes the relevance of specific metabolic pathways to individual intrinsic molecular subtypes of breast cancer. Based on mRNA expression data, the less aggressive luminal subtypes appear to rely on a balance between de novo fatty acid synthesis and oxidation as sources for both biomass and energy requirements, while basal-like, receptor negative subtypes overexpress genes involved in the utilization of exogenous fatty acids. With these differences in mind, treatments may need to be tailored to individual subtypes.

Keywords: breast cancer; fatty acid metabolism; molecular subtype.

Figure 1. Fatty acid metabolism in breast cancer

Color code: Red = genes more highly expressed in TNBC versus RPBC; Blue = genes more highly expressed in RPBC versus TNBC; Green = metabolic substrates. Abbreviations: ACACA: acetyl-CoA carboxylase alpha; ACLY: ATP citrate lyase; ACOX2: acyl-CoA oxidase 2, branched chain; ACSL: long chain fatty acyl-CoA synthetase; CPT1A: carnitine palmitoyltransferase 1A; FABP: fatty acid binding protein; FASN: fatty acid synthase; LPIN1: lipin 1 (also known as phosphatidic acid phosphohydralase (PAP); LPL: lipoprotein lipase; MGLL: monoglyceride lipase; PLA2G4A: phospholipase A2, group IVA (also known as cytosolic phospholipase A2 (cPLA2);PLIN: perilipin; PNPLA2: palatin-like phospholipase domain containing 2 (also known as ATGL, adipocyte triglycderide lipase); SCD1: stearoyl-CoA desaturase 1; SLC2A1: Solute carrier family 2 member 1 (also know as GLUT1, glucose transporter 1); SLC6A14: solute carrier family 6 (amino acid transporter) member 14; SLC27A2: solute carrier family 27 member 2 (also known as ACSVL1, very long chain fatty acyl-CoA synthetase 1), FA: fatty acid; PYR: pyruvate; αKG: alpha ketoglutarate; A-CoA: acetylCoA; FA-CoA: fatty acyl-CoA.