ArticleCancer cell international2024
PPP2R1B abolishes colorectal cancer liver metastasis and sensitizes Oxaliplatin by inhibiting MAPK/ERK signaling pathway.
Article in Cancer cell international, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 9 citations in OpenAlex.
- Metformin suppressed epithelial-mesenchymal transition, cisplatin resistance and metastatic potential of ovarian cancer via inhibiting TGF-β1/Smads.Translational cancer research · 2026Article
- Key molecular mechanisms and regulatory networks in colorectal cancer liver metastasis.Biological procedures online · 2026Review
- EIF4B Ser93 phosphorylation by ERK2 promotes epithelial-mesenchymal transition to drive colorectal cancer metastasis.Cell death & disease · 2026Article
- Preclinical Models of Colorectal Cancer Liver Metastasis: Therapeutic Evaluation and Translational Implications.Oncology research · 2026Review
- Proteome Microarray-Guided Global View: Multiple Pharmacological Targets of Icariin.Drug design, development and therapy · 2026Article
- Prognostic Significance of mTOR Expression in Recurrence Following Hepatic Metastasectomy in Colorectal Cancer.Life (Basel, Switzerland) · 2025Article
- Unraveling Botulinum Neurotoxin A Light-Chain-Induced Signaling Pathways: A Phosphoproteomic Analysis in a Controlled Cellular Model.International journal of molecular sciences · 2025Article
- Expression characteristics, prognostic value, and immune-related analysis of PPP2R1A in lung adenocarcinoma.Frontiers in immunology · 2025Article
- Targeting super-enhancers in liver cancer: from pathogenic mechanisms to clinical applications.Frontiers in pharmacology · 2025Review
- [Colorectal fibroblasts promote malignant phenotype of colorectal cancer cells by activating the ERK signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
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6 authors at 3 institutions in 1 country.
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Abstract
backgroundPatients with colorectal cancer (CRC) with liver metastasis or drug resistance have a poor prognosis. Previous research has demonstrated that PPP2R1B inactivation results in the development of CRC. However, the role of PPP2R1B in CRC metastasis and drug resistance is unclear.
methodsVenny 2.1 was used to determine the intersection between survival-related differentially expressed genes (DEGs) and liver metastasis-related DEGs according to RNA-seq data from The Cancer Genome Atlas (TCGA) and the GEO database (GSE179979). LC‒MS/MS and coimmunoprecipitation were performed to predict and verify the substrate protein of PPP2R1B. Gene Set Variation Analysis (GSVA) was subsequently utilized to assess pathway enrichment levels. The predictive performance of PPP2R1B was assessed by regression analysis, Kaplan-Meier (KM) survival analysis and drug sensitivity analysis. Immunohistochemistry (IHC), qRT-PCR and western blotting were performed to measure the expression levels of related mRNAs or proteins. Biological features were evaluated by wound healing, cell migration and invasion assays and CCK-8 assays. A mouse spleen infection liver metastasis model was generated to confirm the role of PPP2R1B in the progression of liver metastasis in vivo.
resultsAccording to bioinformatics analysis, PPP2R1B is significantly associated with liver metastasis and survival in CRC patients, and these findings were further verified via immunohistochemistry (IHC), qPCR and Western blotting. Pathway enrichment and LC‒MS/MS analysis revealed that PPP2R1B is negatively associated with the MAPK/ERK signalling pathway. Additionally, PD98059, a MAPK/ERK pathway inhibitor, inhibited EMT in vitro by reversing the changes in key proteins involved in EMT signalling (ZEB1, E-cadherin and Snail) and ERK/MAPK signalling (p-ERK) mediated by PPP2R1B. Oxaliplatin sensitivity prediction and validation revealed that PPP2R1B silencing decreased Oxaliplatin chemosensitivity, and these effects were reversed by PD98059 treatment. Moreover, PPP2R1B was coimmunoprecipitated with p-ERK in vitro. A negative correlation between PPP2R1B and p-ERK expression was also observed in clinical CRC samples, and the low PPP2R1B/high p-ERK coexpression pattern indicated a poor prognosis in CRC patients. In vivo, PPP2R1B silencing significantly promoted liver metastasis.
conclusionsThis study revealed that PPP2R1B induces dephosphorylation of the p-ERK protein, inhibits liver metastasis and increases Oxaliplatin sensitivity in CRC patients and could be a potential candidate for therapeutic application in CRC.
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