PPP2R1B abolishes colorectal cancer liver metastasis and sensitizes Oxaliplatin by inhibiting MAPK/ERK signaling pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38429738", "kind": "science-record", "revision": 4, "content_hash": "sha256:4a0e3e74dc6b2367719e4918791c84bad3bd55d3960d8ea4a6ed49c771161d6c", "created_at": "2026-11-01T19:20:22Z", "updated_at": "2026-11-01T22:11:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "PPP2R1B abolishes colorectal cancer liver metastasis and sensitizes Oxaliplatin by inhibiting MAPK/ERK signaling pathway.", "doi": "10.1186/s12935-024-03273-w", "pmid": "38429738", "authors": ["Wei Liu", "Jingtong Tang", "Wei Gao", "Jian Sun", "Gang Liu", "Jianping Zhou"], "journal": "Cancer cell international", "year": 2024, "abstract": "BACKGROUND: Patients 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.\nMETHODS: Venny 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.\nRESULTS: According 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.\nCONCLUSIONS: This 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.", "claims": [{"id": "claim-method", "statement": "Regression analysis revealed a significant negative correlation between the level of PPP2R1B and the level of p-ERK in CRC tissues (Table 2, r = − 0.32, p = 0.001).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38429738", "locator": "sections[23] \"The prognostic value of the combination of PPP2R1B and p-ERK\" paragraph 2", "quote": "Regression analysis revealed a significant negative correlation between the level of PPP2R1B and the level of p-ERK in CRC tissues (Table 2, r = − 0.32, p = 0.001)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Any reasonable requests for access to available data underlying the results reported in this article will be considered. Such proposals should be submitted to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38429738", "locator": "sections[32] \"Availability of data and materials\" paragraph 2", "quote": "Any reasonable requests for access to available data underlying the results reported in this article will be considered. Such proposals should be submitted to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Regression analysis revealed a significant negative correlation between the level of PPP2R1B and the level of p-ERK in CRC tissues (Table 2, r = − 0.32, p = 0.001).", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "Regression analysis revealed a significant negative correlation between the level of PPP2R1B and the level of p-ERK in CRC tissues (Table 2, r = − 0.32, p = 0.001)."}, "evidence": [{"asset": "source:pmid:38429738", "locator": "sections[23] \"The prognostic value of the combination of PPP2R1B and p-ERK\" paragraph 2", "quote": "Regression analysis revealed a significant negative correlation between the level of PPP2R1B and the level of p-ERK in CRC tissues (Table 2, r = − 0.32, p = 0.001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Regression analysis revealed a significant negative correlation between the level of PPP2R1B and the level of p-ERK in CRC tissues (Table 2, r = − 0.32, p = 0.001).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38429738"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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