Figure 1.

LB-100 activates oncogenic signaling, engages stress response pathways, and restrains the proliferation of colorectal cancer cells. A, Gene set enrichment analyses on time-course transcriptome data from HT-29 and SW-480 cells show selected “Hallmarks” and “KEGG” molecular signatures modulated by LB-100 (4 μmol/L). Darker bars indicate time points for which the respective gene set was significantly enriched (P <0.05). B, Time-course western blots show selected oncogenic signaling and stress response pathways modulated by LB-100 (4 μmol/L) in HT-29 and SW-480 cells. α-Tubulin and Vinculin were used as loading controls. C, IncuCyte-based proliferation assays with the colorectal cancer models in the absence or presence of LB-100 at 1, 2, or 4 μmol/L for the indicated times. D, String network combining all hits identified by the two independent genome-wide CRISPR screens (Supplementary Fig. S2) as modulators of LB-100 toxicity. Only high-confidence interactions are shown and disconnected nodes are omitted. Green nodes: CRISPRa screen; orange nodes: CRISPR-KO screen; yellow node: identified on both screens. E, GO analyses using the full list of hits from both CRISPR screens (Supplementary Fig. S2) as input. The top 5 enriched Biological Processes and Molecular Functions terms are shown. Darker bars highlight WNT/β-catenin-and MAPK-related terms.