Fig. 1. PRMT1 is a critical dependency in PDAC.

a Schematic representation of the PILOT platform to inform on patient-centric genetic dependencies. b Venn diagram (4-ellipses) displaying individual and common top-scoring hits across in patient-derived xenograft (PDX) screens in vivo (RSA LogP ≤ −1.5 in at least one PDX and FDR ≤ 0.3). c Gene name and function of the common top 5 scoring hits emerging from the PILOT platform. d Western Blot analysis of PRMT1 expression and mono-methylarginine (MMA) changes in PATC53 cells. Cells were engineered with two independent doxycycline (DOX)-inducible PRMT1-targeting (sh1, sh2) or non-targeting (NT) shRNA, and treated with or without 0.5 µg/mL DOX for 72 h. e Colony formation assay. Representative crystal violet staining image of PATC53 cells engineered with two independent DOX-inducible PRMT1-targeting (sh1, sh2) or non-targeting (NT) shRNA and treated with or without 0.5 µg/mL DOX for 14 days. f Tumor growth curve (mm³) of PATC53 xenografts harboring DOX-inducible PRMT1-targeting (sh1) or non-targeting (NT) control (n = 6 mice/group). Mice were randomized to either a DOX diet (200 mg/Kg) or control chow upon tumor establishment (150 mm³). Data are presented as the mean ± SEM and p values are calculated by 2-way ANOVA with multiple comparisons and Tukey’s correction. g–h Evaluation of PRMT1 expression by immunohistochemistry (scale bar 50 µm, top left corner) (g) and Western Blot analysis (h) in PATC53 tumor lysates 10 days post-DOX-induction. MMA levels are also shown. i Sunburst plot representing the ranked impact, expressed as a percentage of 1/RSA p-value, of the different members of the PRMT family across genetic screens. j–k Effect of CRISPR/Cas9-mediated knock-down of PRMT1, PRMT4, and PRMT6 individually or in combination on global arginine methylation status (j) and on cell growth, as assessed by colony formation assay, in PATC53 cells. Representative crystal violet staining image (k). Source data are provided as a Source Data file.