Disruption of Cytochrome c Oxidase Function Induces Warburg Effect and Metabolic Reprogramming

ABSTRACT: Defects in mitochondrial oxidative phosphorylation complexes, altered bioenergetics and metabolic shift are often seen in cancers. Here we show a role for the dysfunction of electron transport chain component, cytochrome c oxidase (CcO) in cancer progression. We show that genetic silencing of the CcO complex by shRNA expression and loss of CcO activity in multiple cell types from the mouse and human sources resulted in metabolic shift to glycolysis, loss of anchorage dependent growth and acquired invasive phenotypes. Disruption of CcO complex caused loss of transmembrane potential and induction of Ca2+/Calcineurin-mediated retrograde signaling. Propagation of this signaling, includes activation of PI3-kinase, IGF1R and Akt, Ca2+ sensitive transcription factors and also, TGF1, MMP16, perios

ORGANISM(S): Mus musculus

SUBMITTER: Dawei Dong 

PROVIDER: E-GEOD-68525 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress