{"doi":"10.3390/cancers13246169","title":"Transcriptional Regulation of Amino Acid Transport in Glioblastoma Multiforme","abstract":"Glioblastoma multiforme (GBM) is a deadly brain tumor with a large unmet therapeutic need. Here, we tested the hypothesis that wild-type p53 is a negative transcriptional regulator of SLC7A11, the gene encoding the System xc- (SXC) catalytic subunit, xCT, in GBM. We demonstrate that xCT expression is inversely correlated with p53 expression in patient tissue. Using representative patient derived (PDX) tumor xenolines with wild-type, null, and mutant p53 we show that p53 expression negatively correlates with xCT expression. Using chromatin immunoprecipitation studies, we present a molecular interaction whereby p53 binds to the SLC7A11 promoter, suppressing gene expression in PDX GBM cells. Accordingly, genetic knockdown of p53 increases SLC7A11 transcript levels; conversely, over-expressing p53 in p53-null GBM cells downregulates xCT expression and glutamate release. Proof of principal studies in mice with flank gliomas demonstrate that daily treatment with the mutant p53 reactivator, PRIMA-1Met, results in reduced tumor growth associated with reduced xCT expression. These findings suggest that p53 is a molecular switch for GBM glutamate biology, with potential therapeutic utility.","journal":"Cancers","year":2021,"id":191524,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":757846,"name":"Joelle Martin","orcid":null,"position":1,"is_corresponding":false},{"id":757180,"name":"Megan E. Harrigan","orcid":"0000-0001-5160-3686","position":2,"is_corresponding":false},{"id":280570,"name":"Dipan C. Patel","orcid":"0000-0002-1381-5351","position":3,"is_corresponding":false},{"id":655267,"name":"Lata Chaunsali","orcid":"0000-0003-1533-7151","position":4,"is_corresponding":false},{"id":757847,"name":"Aarash K. Roshandel","orcid":null,"position":5,"is_corresponding":false},{"id":757848,"name":"Kavya V. Iyer","orcid":null,"position":6,"is_corresponding":false},{"id":582641,"name":"Michael D. Powell","orcid":"0000-0003-2881-1334","position":7,"is_corresponding":false},{"id":757849,"name":"Ken Oestreich","orcid":null,"position":8,"is_corresponding":false},{"id":280582,"name":"Harald Sontheimer","orcid":"0000-0002-5843-9871","position":9,"is_corresponding":false},{"id":519254,"name":"Robyn A. Umans","orcid":"0000-0001-8862-8887","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:49:35.285023Z","pmid":"34944790","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":[]}