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• W4361824658 abstract "<div>Abstract<p>Because of the refractory nature of mutant <i>KRAS</i> lung adenocarcinoma (LUAD) to current therapies, identification of new molecular targets is essential. Genes with a prognostic role in mutant <i>KRAS</i> LUAD have proven to be potential molecular targets for therapeutic development. Here we determine the clinical, functional, and mechanistic role of inhibitor of differentiation-1 (Id1) in mutant <i>KRAS</i> LUAD. Analysis of LUAD cohorts from TCGA and SPORE showed that high expression of <i>Id1</i> was a marker of poor survival in patients harboring mutant, but not wild-type <i>KRAS</i>. Abrogation of Id1 induced G₂–M arrest and apoptosis in mutant <i>KRAS</i> LUAD cells. <i>In vivo</i>, loss of Id1 strongly impaired tumor growth and maintenance as well as liver metastasis, resulting in improved survival. Mechanistically, Id1 was regulated by the <i>KRAS</i> oncogene through JNK, and loss of Id1 resulted in downregulation of elements of the mitotic machinery via inhibition of the transcription factor FOSL1 and of several kinases within the <i>KRAS</i> signaling network. Our study provides clinical, functional, and mechanistic evidence underscoring <i>Id1</i> as a critical gene in mutant <i>KRAS</i> LUAD and warrants further studies of Id1 as a therapeutic target in patients with LUAD.</p>Significance:<p>These findings highlight the prognostic significance of the transcriptional regulator Id1 in <i>KRAS</i>-mutant lung adenocarcinoma and provide mechanistic insight into how it controls tumor growth and metastasis.</p></div>" @default.
• W4361824658 created "2023-04-05" @default.
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• W4361824658 date "2023-03-31" @default.
• W4361824658 modified "2023-10-18" @default.
• W4361824658 title "Data from Inhibitor of Differentiation-1 Sustains Mutant <i>KRAS</i>-Driven Progression, Maintenance, and Metastasis of Lung Adenocarcinoma via Regulation of a FOSL1 Network" @default.
• W4361824658 doi "https://doi.org/10.1158/0008-5472.c.6511083.v1" @default.
• W4361824658 hasPublicationYear "2023" @default.
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