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Dysregulation of RAS degradation limits the efficacy of RAS inhibitors via reprogramming amino acid sensing machinery

ABSTRACT: To investigate the molecular consequences of LZTR1 loss and its impact on KRAS-regulated signaling, we performed deep proteomic and phosphoproteomic profiling using mass spectrometry. Human tumor cells with CRISPR/Cas9-mediated LZTR1 knockout and their isogenic controls were subjected to tandem mass tag (TMT)-based quantitative proteomic and phosphoproteomic analysis. In parallel, we isolated tumor cells from genetically engineered mouse models harboring KRAS mutations and analyzed their global proteome using label-free quantitative proteomics. These complementary approaches enabled us to systematically characterize changes in protein abundance and phosphorylation status associated with LZTR1 deficiency and to identify pathways potentially involved in resistance to KRAS-targeted therapies.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell

DISEASE(S): Lung Non-squamous Non-small Cell Carcinoma

SUBMITTER: raj sewduth

LAB HEAD: Anna Sablina

PROVIDER: PXD063962 | Pride | 2025-10-09

REPOSITORIES: Pride

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			Action	DRS
	202200505_EV_EVO_MVL_FAIMS_2CV_30SPD_P0017_rerun_RTS_proteome_15.raw	Raw
	202200505_EV_EVO_MVL_FAIMS_2CV_30SPD_P0017_rerun_RTS_proteome_16.raw	Raw
	202200505_EV_EVO_MVL_FAIMS_2CV_30SPD_P0017_rerun_RTS_proteome_17.raw	Raw
	202200505_EV_EVO_MVL_FAIMS_2CV_30SPD_P0017_rerun_RTS_proteome_18.raw	Raw
	202200505_EV_EVO_MVL_FAIMS_2CV_30SPD_P0017_rerun_RTS_proteome_19.raw	Raw

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