Figure 7 from E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network

Therapeutic implications of the MET-E2F1-purine synthesis pathway as a component of the MET-DDR crosstalk. A, Proliferation of EBC-1 and HCC827 cells upon treatments with the indicated doses of tepotinib, cisplatin, and their combination assessed by crystal violet assay 72 hours posttreatment. Data points are represented as mean ± SD of technical replicates (dots). Statistical analyses were done using one-way ANOVA. B, Schematic representation of the proposed MET-E2F1-purine synthesis pathway and its interplay with the DDR in MET-driven cancer cells. MET inhibition by the small-molecule inhibitor tepotinib downregulates E2F1 via the MAPK pathway, consequently downregulating purine synthesis enzymes (e.g., GART) and RNR. This leads to the depletion of dNTPs, compromising the ability of cells to repair DNA damage. Created with BioRender.com.