Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate‐induced apoptosis. Issue 9 (29th August 2018)

• Record Type: Journal Article
• Authors: Balaban, Seher; Lee, Lisa S.; Varney, Bianca; Aishah, Atqiya; Gao, Quanqing; Shearer, Robert F.; Saunders, Darren N.; Grewal, Thomas; Hoy, Andrew J.
• Is Part Of: Molecular oncology. Volume 12:Issue 9(2018)
• Page Start: 1623
• Page End: 1638
• Publication Date: 2018-08-29
• Subjects: breast cancer -- CPT1 -- DGAT -- fatty acid oxidation -- oleate -- triacylglycerols; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12368
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : Breast cancer (BrCa) metabolism is geared toward biomass synthesis and maintenance of reductive capacity. Changes in glucose and glutamine metabolism in BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa biology remains to be determined. We recently reported that adipocyte coculture alters MCF‐7 and MDA‐MB‐231 cell metabolism and promotes proliferation and migration. Since adipocytes are FA‐rich, and these FAs are transferred to BrCa cells, we sought to elucidate the FA metabolism of BrCa cells and their response to FA‐rich environments. MCF‐7 and MDA‐MB‐231 cells incubated in serum‐containing media supplemented with FAs accumulate extracellular FAs as intracellular triacylglycerols (TAG) in a dose‐dependent manner, with MDA‐MB‐231 cells accumulating more TAG. The differences in TAG levels were a consequence of distinct differences in intracellular partitioning of FAs, and not due to differences in the rate of FA uptake. Specifically, MCF‐7 cells preferentially partition FAs into mitochondrial oxidation, whereas MDA‐MB‐231 cells partition FAs into TAG synthesis. These differences in intracellular FA handling underpin differences in the sensitivity to palmitate‐induced lipotoxicity, with MDA‐MB‐231 cells being highly sensitive, whereas MCF‐7 cells are partially protected. The attenuation of palmitate‐induced lipotoxicity in MCF‐7 cells was reversed by inhibition of FA oxidation. Pretreatment of MDA‐MB‐231 cells with FAs increased TAG synthesis and reduced palmitate‐induced apoptosis. Our results provide novel insight into the potential influences of obesity on BrCa biology, highlighting distinct differences in FA metabolism in MCF‐7 and MDA‐MB‐231 cells and how lipid‐rich environments modulate these effects. Abstract : Extracellular fatty acids, alongside glucose and amino acids, are critical substrates for cellular homeostasis. In this study we show heterogeneity in the metabolism of fatty acids in a range of breast cancer cells and that these differences underpin the cell‐specific response to the pro‐apoptotic effects of the saturated fatty acid palmitate.