{"doi":"10.1371/journal.pone.0104821","title":"The p53-Reactivating Small Molecule RITA Induces Senescence in Head and Neck Cancer Cells","abstract":null,"journal":"PLoS ONE","year":2014,"id":648025,"datarank":1.3352091322234911,"base_score":3.367295829986474,"endowment":3.367295829986474,"self_citation_contribution":0.5050943744979712,"citation_network_contribution":0.8301147577255198,"self_endowment_contribution":0.5050943744979712,"citer_contribution":0.8301147577255198,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":23,"citers_with_citation_signal":22,"citers_with_endowment":22,"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":1688570,"name":"Liang Peng Yang","orcid":null,"position":1,"is_corresponding":false},{"id":1183518,"name":"Alison L. Fitzgerald","orcid":"0000-0002-7279-7907","position":2,"is_corresponding":false},{"id":1688572,"name":"Abdullah Osman","orcid":null,"position":3,"is_corresponding":false},{"id":1688573,"name":"Sang Hyeok Woo","orcid":null,"position":4,"is_corresponding":false},{"id":24649,"name":"Jeffrey N. Myers","orcid":"0000-0003-4767-3408","position":5,"is_corresponding":false},{"id":299195,"name":"Heath D. Skinner","orcid":"0000-0003-1836-151X","position":6,"is_corresponding":false},{"id":1665674,"name":"Hui-Ching Chuang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The p53-Reactivating Small Molecule RITA Induces Senescence in Head and Neck Cancer Cells","abstract":"TP53 is the most commonly mutated gene in head and neck cancer (HNSCC), with mutations being associated with resistance to conventional therapy. Restoring normal p53 function has previously been investigated via the use of RITA (reactivation of p53 and induction of tumor cell apoptosis), a small molecule that induces a conformational change in p53, leading to activation of its downstream targets. In the current study we found that RITA indeed exerts significant effects in HNSCC cells. However, in this model, we found that a significant outcome of RITA treatment was accelerated senescence. RITA-induced senescence in a variety of p53 backgrounds, including p53 null cells. Also, inhibition of p53 expression did not appear to significantly inhibit RITA-induced senescence. Thus, this phenomenon appears to be partially p53-independent. Additionally, RITA-induced senescence appears to be partially mediated by activation of the DNA damage response and SIRT1 (Silent information regulator T1) inhibition, with a synergistic effect seen by combining either ionizing radiation or SIRT1 inhibition with RITA treatment. These data point toward a novel mechanism of RITA function as well as hint to its possible therapeutic benefit in HNSCC.","is_dataset_classified":null,"base_score":3.367295829986474,"endowment":3.367295829986474,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25119136","pmcid":"PMC4132078","openalex_id":"https://openalex.org/W1994394906","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"P30 CA016672","title":null}],"total_grants":1,"fwci":1.2427,"citation_percentile":0.78989561,"influential_citations":0,"citation_trend":[{"year":2015,"count":3},{"year":2016,"count":3},{"year":2017,"count":3},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2020,"count":2},{"year":2021,"count":3},{"year":2022,"count":5},{"year":2023,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0104821&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0104821&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0104821","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0104821","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25119136","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.783.4650","host_type":""},{"url":"https://doaj.org/article/2005e656d7ea487abb8a0a395bb10c9d","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4132078","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4132078","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4132078?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cancer-related Molecular Pathways","MicroRNA in disease regulation","RNA Interference and Gene Delivery","Cell Line, Tumor","Cellular Senescence","Furans","Head and Neck Neoplasms","Humans","Immunoblotting","Protein Conformation","Tumor Suppressor Protein p53","beta-Galactosidase"],"mesh_terms":["beta-Galactosidase","Furans","Head and Neck Neoplasms","Humans","Protein Conformation","Immunoblotting","Tumor Suppressor Protein p53","Cellular Senescence","Cell Line, Tumor"],"keywords":["Senescence","Cancer research","Apoptosis","DNA damage","Head and neck squamous-cell carcinoma","Cancer","Biology","Downregulation and upregulation","Head and neck cancer","Cell biology","Gene","DNA","Genetics"],"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":"2026-08-10T02:09:37.594860Z","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":[]}