{"doi":"10.1038/nature03918","title":"Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis","abstract":null,"journal":"Nature","year":2005,"id":589463,"datarank":17.382874122587822,"base_score":7.592366128519796,"endowment":7.592366128519796,"self_citation_contribution":1.1388549192779696,"citation_network_contribution":16.244019203309854,"self_endowment_contribution":1.1388549192779696,"citer_contribution":16.244019203309854,"corpus_percentile":null,"corpus_rank":null,"citation_count":1982,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":266281,"name":"Lloyd C. Trotman","orcid":"0000-0002-4794-1559","position":1,"is_corresponding":false},{"id":816779,"name":"David Shaffer","orcid":null,"position":2,"is_corresponding":false},{"id":1452471,"name":"Hui-Kuan Lin","orcid":null,"position":3,"is_corresponding":false},{"id":1508171,"name":"Zohar A. Dotan","orcid":null,"position":4,"is_corresponding":false},{"id":1508172,"name":"Masaru Niki","orcid":null,"position":5,"is_corresponding":false},{"id":478743,"name":"Jason A. Koutcher","orcid":"0000-0002-1399-5065","position":6,"is_corresponding":false},{"id":90756,"name":"Howard I. Scher","orcid":"0000-0002-6791-9324","position":7,"is_corresponding":false},{"id":71143,"name":"Thomas Ludwig","orcid":"0000-0003-4020-6321","position":8,"is_corresponding":false},{"id":57914,"name":"William Gerald","orcid":null,"position":9,"is_corresponding":false},{"id":13004,"name":"Carlos Cordon-Cardo","orcid":null,"position":10,"is_corresponding":false},{"id":23892,"name":"Pier Paolo Pandolfi","orcid":"0000-0002-5352-5295","position":11,"is_corresponding":false},{"id":1083609,"name":"Zhenbang Chen","orcid":"0000-0002-7030-2691","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis","abstract":"Cellular senescence has been theorized to oppose neoplastic transformation triggered by activation of oncogenic pathways in vitro, but the relevance of senescence in vivo has not been established. The PTEN and p53 tumour suppressors are among the most commonly inactivated or mutated genes in human cancer including prostate cancer. Although they are functionally distinct, reciprocal cooperation has been proposed, as PTEN is thought to regulate p53 stability, and p53 to enhance PTEN transcription. Here we show that conditional inactivation of Trp53 in the mouse prostate fails to produce a tumour phenotype, whereas complete Pten inactivation in the prostate triggers non-lethal invasive prostate cancer after long latency. Strikingly, combined inactivation of Pten and Trp53 elicits invasive prostate cancer as early as 2 weeks after puberty and is invariably lethal by 7 months of age. Importantly, acute Pten inactivation induces growth arrest through the p53-dependent cellular senescence pathway both in vitro and in vivo, which can be fully rescued by combined loss of Trp53. Furthermore, we detected evidence of cellular senescence in specimens from early-stage human prostate cancer. Our results demonstrate the relevance of cellular senescence in restricting tumorigenesis in vivo and support a model for cooperative tumour suppression in which p53 is an essential failsafe protein of Pten-deficient tumours.","is_dataset_classified":null,"base_score":7.592366128519796,"endowment":7.592366128519796,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16079851","pmcid":"PMC1939938","openalex_id":"https://openalex.org/W1982395176","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"P50 CA092629","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA137050","title":null},{"funder_name":"NIMHD NIH HHS","grant_id":"R01 MD004038","title":null}],"total_grants":3,"fwci":40.6185,"citation_percentile":0.99924746,"influential_citations":0,"citation_trend":[{"year":2012,"count":117},{"year":2013,"count":125},{"year":2014,"count":123},{"year":2015,"count":110},{"year":2016,"count":105},{"year":2017,"count":83},{"year":2018,"count":91},{"year":2019,"count":90},{"year":2020,"count":94},{"year":2021,"count":75},{"year":2022,"count":81},{"year":2023,"count":95},{"year":2024,"count":74},{"year":2025,"count":66},{"year":2026,"count":24}],"oa_status":"green","license":"http://www.springer.com/tdm","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1939938","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1939938","host_type":"repository"},{"url":"http://www.nature.com/articles/nature03918.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/nature03918","host_type":"publisher"},{"url":"https://doi.org/10.1038/nature03918","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16079851","host_type":"repository"},{"url":"https://repository.cshl.edu/id/eprint/27770/","host_type":"repository"},{"url":"https://www.nature.com/articles/nature03918","host_type":"repository"}],"fields_of_study":["Cancer-related Molecular Pathways","Telomeres, Telomerase, and Senescence","Genomics and Chromatin Dynamics","ADP-Ribosylation Factors","Animals","Cell Transformation, Neoplastic","Cells, Cultured","Cellular Senescence","Female","Fibroblasts","Male","Mice","PTEN Phosphohydrolase","Phenotype","Phosphoric Monoester Hydrolases","Prostatic Neoplasms","Survival Analysis","Tumor Suppressor Protein p53","Tumor Suppressor Proteins"],"mesh_terms":["Animals","Cell Transformation, Neoplastic","Cells, Cultured","Female","Fibroblasts","Male","Phenotype","Phosphoric Monoester Hydrolases","Prostatic Neoplasms","Survival Analysis","Tumor Suppressor Protein p53","Cellular Senescence","ADP-Ribosylation Factors","Tumor Suppressor Proteins","PTEN Phosphohydrolase","Mice"],"keywords":["PTEN","Senescence","Carcinogenesis","Cancer research","Biology","Prostate cancer","Prostate","Cancer","In vivo","Transcription factor","Phenotype","Cell biology","Gene","Genetics","Signal transduction","PI3K/AKT/mTOR pathway"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-23T18:49:20.897793Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}