FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4320178725> ?p ?o ?g. }

• W4320178725 abstract "ABSTRACT Ferroptosis, a form of non-apoptotic cell death program driven by excessive lipid peroxidation and an important mechanism of tumor suppression, is frequently dysregulated in cancer. However, the mechanisms underlying impaired ferroptosis in oncogene-specific tumors remain poorly understood. Here we report a non- canonical role of lactate dehydrogenase B (LDHB), whose main activity is the conversion of lactate to pyruvate, in protecting KRAS-mutated lung cancer from ferroptosis. Silencing of LDHB impairs intracellular glutathione (GSH) metabolism and drives the hypersensitivity of KRAS -mutant cells to ferroptosis inducers by inhibiting the SLC7A11/GSH/GPX4 axis, a central antioxidant system against lipid peroxidation and ferroptosis by catalyzing GSH synthesis and utilization. Mechanistically, LDHB promotes SLC7A11 expression and GSH biosynthesis, and inhibition of LDHB confers metabolic synthetic lethality with ferroptosis inducers due to increased glutaminolysis and production of reactive oxygen species (ROS) in mitochondria, ultimately triggering ferroptosis of KRAS -driven lung cancer cells. Consequently, combined inhibition of LDHB and SLC7A11 synergistically suppresses tumor growth in multiple KRAS -mutant lung cancer implants and in an autochthonous model of Kras -induced lung adenocarcinoma. Taken together, our results reveal a hitherto unrecognized mechanism of ferroptosis defense by glycolytic LDHB and suggest a new strategy for the treatment of KRAS -dependent lung cancer." @default.
• W4320178725 created "2023-02-13" @default.
• W4320178725 creator A5013484162 @default.
• W4320178725 creator A5025823556 @default.
• W4320178725 creator A5037336704 @default.
• W4320178725 creator A5039127180 @default.
• W4320178725 creator A5047807741 @default.
• W4320178725 creator A5051351970 @default.
• W4320178725 creator A5062025470 @default.
• W4320178725 creator A5066368213 @default.
• W4320178725 creator A5069553823 @default.
• W4320178725 creator A5072556453 @default.
• W4320178725 creator A5080089616 @default.
• W4320178725 creator A5084203689 @default.
• W4320178725 creator A5084929058 @default.
• W4320178725 creator A5084939122 @default.
• W4320178725 creator A5088482310 @default.
• W4320178725 creator A5089920309 @default.
• W4320178725 date "2023-02-12" @default.
• W4320178725 modified "2023-10-06" @default.
• W4320178725 title "A non-canonical function of LDHB promotes SLC7A11-mediated glutathione metabolism and protects against glutaminolysis-dependent ferroptosis in<i>KRAS</i>-driven lung cancer" @default.
• W4320178725 cites W1589007430 @default.
• W4320178725 cites W1964959571 @default.
• W4320178725 cites W1970766774 @default.
• W4320178725 cites W1982330633 @default.
• W4320178725 cites W1992724001 @default.
• W4320178725 cites W1997183854 @default.
• W4320178725 cites W2002490399 @default.
• W4320178725 cites W2009999719 @default.
• W4320178725 cites W2096294661 @default.
• W4320178725 cites W2101228747 @default.
• W4320178725 cites W2114138419 @default.
• W4320178725 cites W2124813314 @default.
• W4320178725 cites W2128339707 @default.
• W4320178725 cites W2149519422 @default.
• W4320178725 cites W2184384535 @default.
• W4320178725 cites W2223535266 @default.
• W4320178725 cites W2284388501 @default.
• W4320178725 cites W2291790203 @default.
• W4320178725 cites W2519232588 @default.
• W4320178725 cites W2519338564 @default.
• W4320178725 cites W2523989131 @default.
• W4320178725 cites W2534904302 @default.
• W4320178725 cites W2606901660 @default.
• W4320178725 cites W2620892894 @default.
• W4320178725 cites W2742797230 @default.
• W4320178725 cites W2762087180 @default.
• W4320178725 cites W2764232556 @default.
• W4320178725 cites W2777598902 @default.
• W4320178725 cites W2796148399 @default.
• W4320178725 cites W2804040141 @default.
• W4320178725 cites W2889171823 @default.
• W4320178725 cites W2912580313 @default.
• W4320178725 cites W2913235593 @default.
• W4320178725 cites W2940348880 @default.
• W4320178725 cites W2941550709 @default.
• W4320178725 cites W2943793201 @default.
• W4320178725 cites W2988805363 @default.
• W4320178725 cites W2992908616 @default.
• W4320178725 cites W2998103954 @default.
• W4320178725 cites W2998854578 @default.
• W4320178725 cites W3000233190 @default.
• W4320178725 cites W3013377779 @default.
• W4320178725 cites W3015020891 @default.
• W4320178725 cites W3016702666 @default.
• W4320178725 cites W3033153720 @default.
• W4320178725 cites W3045511770 @default.
• W4320178725 cites W3072295979 @default.
• W4320178725 cites W3090693089 @default.
• W4320178725 cites W3096650868 @default.
• W4320178725 cites W3101330565 @default.
• W4320178725 cites W3108493784 @default.
• W4320178725 cites W3109926818 @default.
• W4320178725 cites W3118092388 @default.
• W4320178725 cites W3123922203 @default.
• W4320178725 cites W3138007187 @default.
• W4320178725 cites W3162306949 @default.
• W4320178725 cites W3171675220 @default.
• W4320178725 cites W3180882383 @default.
• W4320178725 cites W4200173198 @default.
• W4320178725 cites W4205672295 @default.
• W4320178725 cites W4221112683 @default.
• W4320178725 cites W4225162256 @default.
• W4320178725 cites W4280572279 @default.
• W4320178725 cites W4287092179 @default.
• W4320178725 cites W4288068925 @default.
• W4320178725 cites W4292787442 @default.
• W4320178725 cites W4293176236 @default.
• W4320178725 cites W4303446545 @default.
• W4320178725 cites W4310463888 @default.
• W4320178725 cites W903460745 @default.
• W4320178725 doi "https://doi.org/10.1101/2023.02.12.525859" @default.
• W4320178725 hasPublicationYear "2023" @default.
• W4320178725 type Work @default.
• W4320178725 citedByCount "1" @default.
• W4320178725 countsByYear W43201787252023 @default.
• W4320178725 crossrefType "posted-content" @default.
• W4320178725 hasAuthorship W4320178725A5013484162 @default.
• W4320178725 hasAuthorship W4320178725A5025823556 @default.
• W4320178725 hasAuthorship W4320178725A5037336704 @default.

• next