Journal: bioRxiv
Article Title: Baseline cellular state dictates the molecular impact of KRAS mutant variants in pancreatic cancer cells
doi: 10.64898/2026.03.10.710185
Figure Lengend Snippet: Baseline cellular state dictates the impact of mutant KRAS expression. (A) Unsupervised hierarchical clustering of transcriptomic, proteomic, and phosphoproteomic datasets show that clone origin, not KRAS allele, is the major driver of sample segregation, even between clones derived from the same parental line. Color scale denotes row-normalized absolute abundance. (B) UpSet plots showing the overlap of significantly upregulated (top) and downregulated (bottom) genes (transcriptome), proteins (proteome), and phosphosites (phosphoproteome) across all four reconstituted cell lines. A fold change ≥ 1.3 and adjusted p -value ≤ 0.05 threshold were used to determine differential expression of all KRAS MUT relative to KRAS WT for at least two cell lines. Each bar represents the number of shared or unique differentially expressed features between clones. Shared upregulated and downregulated features highlight the limited global convergence of KRAS-dependent molecular responses across cell lines. (C) Quantification of pERK1/2 (T202/Y204) and pAKT (S473) levels relative to total ERK and AKT levels in each cell line. The ratios (geometric means ± geometric SD) of the expression KRAS MUT (n = 7 mutants) relative to KRAS WT (average of n = 3 biologic replicates) for each cell lines are shown. p -values are derived from Brown-Forsythe lognormal ANOVA with Games-Howell’s post-hoc test.
Article Snippet: The following antibodies were used for immunoblotting: rabbit anti-HSP90 (Cell Signaling Technologies (CST), 4877, 1:10,000), rabbit anti-pERK1/2 (T202/Y204) (CST, 4370, 1:2000), mouse anti-ERK1/2 (CST, 9107, 1:1000), rabbit anti-pAKT (S473) (CST, 4060, 1:1000), mouse anti-AKT (CST, 2966, 1:2000), mouse anti-KRAS (Sigma-Aldrich, 3B10-2F2, 1:1000).
Techniques: Mutagenesis, Expressing, Clone Assay, Derivative Assay, Quantitative Proteomics
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