ArticleEMBO reports2024
The phosphatase inhibitor LB-100 creates neoantigens in colon cancer cells through perturbation of mRNA splicing.
Article in EMBO reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Protein phosphatase 2A regulates senescence and immunogenicity in medulloblastoma models.The Journal of clinical investigation · 2026Article
- The Protein Phosphatase Inhibitor LB100 Targets the Mesenchymal Lineage of Pancreatic Ductal Adenocarcinoma.MedComm · 2026Article
- Native long-read RNA sequencing of human monocytes reveals activation-induced alternative splicing toward functional isoforms.Nature communications · 2026Article
- The role of PPP2R1A variants in gynecologic malignancies: a paradigm shift in immuno-oncology.Journal of translational medicine · 2026Review
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- On the history, synthesis, and medicinal use of cantharidin, LB-100, and their analogs.RSC medicinal chemistry · 2026Review
- Non-canonical and induced neoantigens as emerging sources of cancer-specific immunotherapy targets.Frontiers in immunology · 2026Review
- MYC at the tumor-immune interface: mechanisms of immune escape and immunotherapy resistance.Frontiers in immunology · 2026Review
- Synergistic Efficacy of Chidamide and LB100 in Sézary Syndrome via TNC Downregulation and PI3K/AKT/mTOR Dephosphorylation.Cancer science · 2025Article
- Targeting PP2A in cancer: an underrated option.Journal of experimental & clinical cancer research : CR · 2025Review
- A single gene mutation predicts response to immune checkpoint blockade in ovarian clear cell carcinoma.Molecular oncology · 2025Article
- PROTEIN PHOSPHATASE 2A B'η drives spliceosome subunit dephosphorylation to mediate alternative splicing following heat stress.The Plant cell · 2025Article
- LB-100 Enhances Drugs Efficacy Through Inhibition of P-Glycoprotein Expression in Multidrug-Resistant Glioblastoma and Non-Small Cell Lung Carcinoma Cellular Models.Pharmaceutics · 2025Article
- Tumor-promoting effect and tumor immunity of SRSFs.Frontiers in cell and developmental biology · 2025Review
- Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.Theranostics · 2025Review
- A combination of protein phosphatase 2A inhibition and checkpoint immunotherapy: a perfect storm.Molecular oncology · 2024Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
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 phosphorylation endows LB-100-treated colorectal adenocarcinoma cells with differential splicing patterns. In PP2A-inhibited cells, over 1000 events of exon skipping and intron retention affect regulators of genomic integrity. Finally, we show that LB-100-evoked alternative splicing leads to neoantigens that are presented by MHC class 1 at the cell surface. Our findings provide a potential explanation for the pre-clinical and clinical observations that LB-100 sensitizes cancer cells to immune checkpoint blockade.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.