Matches in SemOpenAlex for { <https://semopenalex.org/work/W4220993876> ?p ?o ?g. }
- W4220993876 endingPage "982" @default.
- W4220993876 startingPage "959" @default.
- W4220993876 abstract "Mutations in genes encoding cytochrome c oxidase (mitochondrial complex IV) subunits and assembly factors [e.g., synthesis of cytochrome c oxidase 2 (SCO2)] are linked to severe metabolic syndromes. Notwithstanding that SCO2 is under transcriptional control of tumor suppressor p53, the role of mitochondrial complex IV dysfunction in cancer metabolism remains obscure. Herein, we demonstrate that the loss of SCO2 in HCT116 colorectal cancer cells leads to significant metabolic and signaling perturbations. Specifically, abrogation of SCO2 increased NAD + regenerating reactions and decreased glucose oxidation through citric acid cycle while enhancing pyruvate carboxylation. This was accompanied by a reduction in amino acid levels and the accumulation of lipid droplets. In addition, SCO2 loss resulted in hyperactivation of the insulin‐like growth factor 1 receptor (IGF1R)/AKT axis with paradoxical downregulation of mTOR signaling, which was accompanied by increased AMP‐activated kinase activity. Accordingly, abrogation of SCO2 expression appears to increase the sensitivity of cells to IGF1R and AKT, but not mTOR inhibitors. Finally, the loss of SCO2 was associated with reduced proliferation and enhanced migration of HCT116 cells. Collectively, herein we describe potential adaptive signaling and metabolic perturbations triggered by mitochondrial complex IV dysfunction." @default.
- W4220993876 created "2022-04-03" @default.
- W4220993876 creator A5000806913 @default.
- W4220993876 creator A5003512614 @default.
- W4220993876 creator A5011530890 @default.
- W4220993876 creator A5022922854 @default.
- W4220993876 creator A5035426339 @default.
- W4220993876 creator A5048877173 @default.
- W4220993876 creator A5050369210 @default.
- W4220993876 creator A5065592637 @default.
- W4220993876 creator A5066083924 @default.
- W4220993876 creator A5068757963 @default.
- W4220993876 creator A5069018562 @default.
- W4220993876 creator A5083273593 @default.
- W4220993876 creator A5083890315 @default.
- W4220993876 date "2022-04-01" @default.
- W4220993876 modified "2023-10-06" @default.
- W4220993876 title "Mitochondrial complex IV defects induce metabolic and signaling perturbations that expose potential vulnerabilities in HCT116 cells" @default.
- W4220993876 cites W1524076404 @default.
- W4220993876 cites W1540878808 @default.
- W4220993876 cites W1553978925 @default.
- W4220993876 cites W1801184284 @default.
- W4220993876 cites W1916910865 @default.
- W4220993876 cites W1932780354 @default.
- W4220993876 cites W1967291345 @default.
- W4220993876 cites W1975557286 @default.
- W4220993876 cites W1978774712 @default.
- W4220993876 cites W1980438140 @default.
- W4220993876 cites W1983877797 @default.
- W4220993876 cites W1984164475 @default.
- W4220993876 cites W1986273448 @default.
- W4220993876 cites W1995675594 @default.
- W4220993876 cites W2000697370 @default.
- W4220993876 cites W2001568034 @default.
- W4220993876 cites W2003723306 @default.
- W4220993876 cites W2014058353 @default.
- W4220993876 cites W2016360721 @default.
- W4220993876 cites W2024857001 @default.
- W4220993876 cites W2025719835 @default.
- W4220993876 cites W2028743750 @default.
- W4220993876 cites W2037583144 @default.
- W4220993876 cites W2057199368 @default.
- W4220993876 cites W2061059838 @default.
- W4220993876 cites W2061662711 @default.
- W4220993876 cites W2062515127 @default.
- W4220993876 cites W2063011414 @default.
- W4220993876 cites W2080452140 @default.
- W4220993876 cites W2081920342 @default.
- W4220993876 cites W2082959665 @default.
- W4220993876 cites W2086338749 @default.
- W4220993876 cites W2088417711 @default.
- W4220993876 cites W2092087129 @default.
- W4220993876 cites W2092715210 @default.
- W4220993876 cites W2095454212 @default.
- W4220993876 cites W2101075480 @default.
- W4220993876 cites W2102050179 @default.
- W4220993876 cites W2114086633 @default.
- W4220993876 cites W2119239003 @default.
- W4220993876 cites W2120963683 @default.
- W4220993876 cites W2121727754 @default.
- W4220993876 cites W2122826701 @default.
- W4220993876 cites W2127629715 @default.
- W4220993876 cites W2128518955 @default.
- W4220993876 cites W2128607432 @default.
- W4220993876 cites W2143017330 @default.
- W4220993876 cites W2155408196 @default.
- W4220993876 cites W2158389310 @default.
- W4220993876 cites W2160757449 @default.
- W4220993876 cites W2166337262 @default.
- W4220993876 cites W2223724347 @default.
- W4220993876 cites W2294704562 @default.
- W4220993876 cites W2338181945 @default.
- W4220993876 cites W2410228837 @default.
- W4220993876 cites W2422376409 @default.
- W4220993876 cites W2503844550 @default.
- W4220993876 cites W2510661803 @default.
- W4220993876 cites W2517861725 @default.
- W4220993876 cites W2530859476 @default.
- W4220993876 cites W2554348994 @default.
- W4220993876 cites W2586265133 @default.
- W4220993876 cites W2587679548 @default.
- W4220993876 cites W2594191418 @default.
- W4220993876 cites W2606795822 @default.
- W4220993876 cites W2746172096 @default.
- W4220993876 cites W2761245997 @default.
- W4220993876 cites W2771930478 @default.
- W4220993876 cites W2782192099 @default.
- W4220993876 cites W2884382839 @default.
- W4220993876 cites W2891587993 @default.
- W4220993876 cites W2951317843 @default.
- W4220993876 cites W2995820602 @default.
- W4220993876 cites W2996068296 @default.
- W4220993876 cites W2996724088 @default.
- W4220993876 cites W2999421965 @default.
- W4220993876 cites W3015450697 @default.
- W4220993876 cites W3043817571 @default.
- W4220993876 cites W3092206934 @default.
- W4220993876 cites W3094521060 @default.