ACYL-COA SYNTHETASE 4 MODULATES GLYCOLYTIC FUNCTION AND MITOCHONDRIAL METABOLISM IN BREAST CANCER CELLS

BENZO Y; PRADA J; DATTILO MA; LOPEZ P; CASTILLO AF; MORI SEQUEIROS GARCÍA MM; PODEROSO C; MALOBERTI PM

Mar del PLata

Congreso; LXVII ANNUAL MEETING OF SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC).; 2022

SAIC

The relationship between cancer and mitochondrial function hasbeen widely demonstrated. Mitochondrial dysfunction is associatedwith oncogenesis and cancer development mainly by the prevalenceof anaerobic glycolysis even under normoxia (Warburg effect). Inbreast cancer, Acyl-CoA synthetase 4 (ACSL4), an enzyme involvedin arachidonic acid metabolism, promotes tumor aggressiveness.Previously, we demonstrated in MCF-7 breast cancer cells thatstable overexpression of ACSL4 significantly increases the levelsof mitochondrial markers, mitochondrial activity and respiratory parameterssuch as proton leak, maximal respiration, and spare respiratorycapacity (p˂ 0.05, p˂0.01) respective to control cells. Theaim of this work is to determine whether glycolytic function and mitochondrialmetabolism are modulated by ACSL4 in breast cancercells. For this purpose, Seahorse XF Glycolysis Stress Test wascarried out to measure extra acidification rate (ECAR) and glycolyticparameters. Our results showed a significant increase in glycolyticfunction, non- glycolytic acidification, and glycolysis (p˂0.05, p˂0.01)and an increase in glycolytic capacity in MCF-7 overexpressingACSL4. Furthermore, ACSL4 induced a significant decrease in thepercentage of glycolytic reserve (p˂ 0.05) relative to control cells.These results corroborate a role of ACSL4 in glycolytic functionin MCF-7 breast cancer cells. Also, we observed a significant increase(p˂ 0.05) in mRNA levels of mitochondrial genes related tomitochondrial function such as NRF-1/2, UCP2 and ANT1 in MCF-7 overexpressing ACSL4 cells (p˂0.05). In conclusion, our work suggeststhat ACSL4 could confer an adaptive advantage to tumor cellsby inducing glycolytic metabolism favoring tumor development andcould protect mitochondria by promoting the expression of biogenesisgenes. These results expand our knowledge of the role of ACSL4in glycolytic function and metabolism of mitochondria in breast cancercells.