MnSOD upregulation sustains the Warburg effect via.pdf (2.04 MB)
Download fileMnSOD upregulation sustains the Warburg effect via mitochondrial ROS and AMPK-dependent signalling in cancer
journal contribution
posted on 2016-01-21, 00:00 authored by P.C. Hart, M. Mao, A.L. de Abreu, Kristine Ansenberger-Fricano, D.N. Ekoue, D. Ganini, A. Kajdacsy-BallaManganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that
governs the types of reactive oxygen species egressing from the organelle to affect cellular
signalling. Here we demonstrate that MnSOD upregulation in cancer cells establishes a
steady flow of H2O2 originating from mitochondria that sustains AMP-activated kinase
(AMPK) activation and the metabolic shift to glycolysis. Restricting MnSOD expression or
inhibiting AMPK suppresses the metabolic switch and dampens the viability of transformed
cells indicating that the MnSOD/AMPK axis is critical to support cancer cell bioenergetics.
Recapitulating in vitro findings, clinical and epidemiologic analyses of MnSOD expression and
AMPK activation indicated that the MnSOD/AMPK pathway is most active in advanced stage
and aggressive breast cancer subtypes. Taken together, our results indicate that MnSOD
serves as a biomarker of cancer progression and acts as critical regulator of tumour cell
metabolism.