biostudies-literatureDias MHX-omics InitiativeDutch Ministry of Health, Welfare and SportLixte Biotechnology HoldingsDutch Cancer SocietyNational Science CenterOncode Institute2220-2238https://www.ebi.ac.uk/biostudies/studies/S-EPMC11094086biostudies-literatureUnknown25(5)Perturbation of protein phosphorylation represents an attractive approach to cancer treatment. Besides kinase inhibitors, protein phosphatase inhibitors have been shown to have anti-cancer activity. A prime example is the small molecule LB-100, an inhibitor of protein phosphatases 2A/5 (PP2A/PP5), enzymes that affect cellular physiology. LB-100 has proven effective in pre-clinical models in combination with immunotherapy, but the molecular underpinnings of this synergy remain understood poorly. We report here a sensitivity of the mRNA splicing machinery to phosphorylation changes in response to LB-100 in colorectal adenocarcinoma. We observe enrichment for differentially phosphorylated sites within cancer-critical splicing nodes of U2 snRNP, SRSF and hnRNP proteins. Altered phosphorylationEMBO reportsThe phosphatase inhibitor LB-100 creates neoantigens in colon cancer cells through perturbation of mRNA splicing.PMC11094086UMO-2022/46/E/NZ3/00141UMO-2021/43/B/NZ3/01177Project 184.034.019Rene R BernardsLiudkovska VDias MHPapagianni CMontenegro Navarro JChampagne JAgami RCiesla MBleijerveld OBGiebel LVelds ABernards RfalseThe phosphatase inhibitor LB-100 creates neoantigens in colon cancer cells through perturbation of mRNA splicing.Perturbation of protein phosphorylation represents an attractive approach to cancer treatment. Besides kinase inhibitors, protein phosphatase inhibitors have been shown to have anti-cancer activity. A prime example is the small molecule LB-100, an inhibitor of protein phosphatases 2A/5 (PP2A/PP5), enzymes that affect cellular physiology. LB-100 has proven effective in pre-clinical models in combination with immunotherapy, but the molecular underpinnings of this synergy remain understood poorly. We report here a sensitivity of the mRNA splicing machinery to phosphorylation changes in response to LB-100 in colorectal adenocarcinoma. We observe enrichment for differentially phosphorylated sites within cancer-critical splicing nodes of U2 snRNP, SRSF and hnRNP proteins. Altered phosphorylation2024-01-01T00:00:00Z2024 May2026-06-03T06:54:15.995Z2026-04-25T03:22:34.703ZS-EPMC110940863860034510.1038/s44319-024-00128-3