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. 2022 Jun 8;13:3181. doi: 10.1038/s41467-022-30794-7

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — A Alpelisib and PF-04691502 dose-response curves in either RNF43^659mut edited cells (HT29, LS513) or ectopically expressing (OE) RNF43_G659Vfs*41 cells (HCT116) compared to controls. Experiments were performed in triplicate. B Dose-response curve of alpelisib and PF-04691502, along with an MDM2 antagonist and MEK, tankyrase, and PORCN inhibitors, in patient-derived CRC organoids harboring RNF43_G659fs and normal colon organoids. C Image representation of mouse tumor size after placebo or PF-04691502 treatment in cell-derived xenografts harboring either HT29 sg_Ctrl or HT29 sg_RNF43^659mut. D Quantification of tumor weight after placebo or PF-04691502 treatment in cell-derived xenograft harboring either HT29 sg_Ctrl or HT29 sg_RNF43^659mut. Data are the mean ± SD. Two-sided Student’s t test (n = 5 mice/group). E Representative immunohistochemistry images of p-AKT (S473), Ki-67 and TUNEL-positive cells in HT29_sg-Ctrl or HT29_RNF43^659mut-C1 tumors from mice treated with vehicle or PF-04691502. Scale bar 10 μm. Source data are provided as a Source Data file.