Cell Type–specific Adaptive Signaling Responses to KRAS^G12C Inhibition

Supplementary Data

• Supplementary Table S1 - Supplementary Table S1. Relative quantification of peptides representing total KRAS, WT KRAS, free KRAS G12C protein and drug bound KRAS G12C Protein Levels.
• Supplementary Table S2 - Supplementary Table S2. The complete list of identified phosphopeptides after (pY) enrichment in ARS-1620 treated cells with fold change quantisation and p-value calculation.
• Supplementary Table S3 - Supplementary Table S3. The complete list of identified phosphopeptides after global (pS/T/Y) phosphopeptides enrichment in ARS-1620 treated cells with fold change quantisation and p-value calculation.
• Supplementary Table S4 - Supplementary Table S4. The complete list of identified phosphopeptides after (pY) enrichment and TMT-based quantitative phosphoproteomics analysis in KRASG12C mutant lung cancer cell lines (n=8) with mean-centered log abundance values.
• Supplementary Table S5 - Supplementary Table S5. The complete list of identified proteins after TMT-based quantitative proteomic analysis in KRASG12C mutant lung cancer cell lines (n=8) with mean-centered log abundance values.
• Supplementary Table S6 - Supplementary Table S6. LC-MRM quantification of peptides representing CDH1 and CDH2 expression in H358, Calu1 and H1792 cells.
• Supplementary Table S7 - Supplementary Table S7. The mean-centered CCLE normalized log2 RNA-seq counts for indicated genes and TGFβ-EMT analysis of 15 KRASG12C NSCLC cell lines.
• Supplementary Table S8 - Supplementary Table S8. The TGFβ-EMT analysis of 8 KRASG12C lung cancer cell lines.
• Supplementary Table S9 - Supplementary Table S9. The correlation analysis between ERBB2/ERBB3 and EMT score in SPORE 442 KRASG12C lung cancer mutants.
• Legends to Supplementary Data - Legends to Supplementary Figures and Tables
• Supplementary Methods - Detailed Supplementary Methods
• Supplementary Figures - Supplementary Fig. S1. Differential response (2D and 3D culture) of KRASG12C specific covalent inhibitors (ARS-1620 and AMG510) in KRASG12C lung cancer cell lines and signaling rebound following KRASG12C inhibition. Supplementary Fig. S2. MetaCore literature network after ARS-1620 treatment in H358 cells. Supplementary Fig. S3. TMT design for expression and pY comparison in 8 KRASG12C lung cancer cell lines and two group comparison of phosphosites Supplementary Fig. S4. Analysis of CCLE data set for EMT markers and ERBB3 gene expression; and PCA representing 105 probeset TGFβ-EMT signatures (Gordian et al. 2019) translated into proteins expression to describe EMT activity in KRASG12C lung cancer cell lines. Supplementary Fig. S5. Impact of SHP2 inhibitors (SHP-099 and RMC-4550) on signaling in H358 cells and cell viability analysis following treatment with SHP2 inhibitors or in the combination with ARS-1620 in H358 and H1792 cells. Supplementary Fig. S6. Literature-based signaling network after KRASG12C inhibition in H1792 cells and cell viability analysis following treatment with ARS-1620 (1µM), AZD-4547 (1µM) and their combination in NSCLCG12C mutant cell lines. Supplementary Fig. S7. Effect of TGFβ stimulation on cell viability in response to KRASG12C inhibition and different combination strategies. Supplementary Fig. S8. Heatmap showing mean-centered log abundance expression values for indicated phosphosites/protein expression in KRASG12C mutant cell lines and E vs M 2-group comparison performed for FGFR1 gene expression in CCLE data set. Supplementary Fig. S9. Literature-based signaling network after KRASG12C inhibition in Calu1 cells and impact on signaling following treatment with ARS-1620 plus drugs known to target AXL Receptor.