{"doi":"10.1101/2024.02.20.581224","title":"p300 KAT regulates SOX10 stability and function in human melanoma","abstract":"Abstract SOX10 is a lineage-specific transcription factor critical for melanoma tumor growth, while SOX10 loss-of-function drives the emergence of therapy-resistant, invasive melanoma phenotypes. A major challenge has been developing therapeutic strategies targeting SOX10’s role in melanoma proliferation, while preventing a concomitant increase in tumor cell invasion. Here, we report that the lysine acetyltransferase (KAT) EP300 and SOX10 gene loci on Chromosome 22 are frequently co-amplified in melanomas, including UV-associated and acral tumors. We further show that p300 KAT activity mediates SOX10 protein stability and that the p300 inhibitor, A-485, downregulates SOX10 protein levels in melanoma cells via proteasome-mediated degradation. Additionally, A-485 potently inhibits proliferation of SOX10+ melanoma cells while decreasing invasion in AXL high /MITF low melanoma cells through downregulation of metastasis-related genes. We conclude that the SOX10/p300 axis is critical to melanoma growth and invasion, and that inhibition of p300 KAT activity through A-485 may be a worthwhile therapeutic approach for SOX10-reliant tumors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":494662,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1256575,"name":"Nicole Grbic","orcid":"0000-0001-5641-2934","position":1,"is_corresponding":false},{"id":1230229,"name":"Kassidy Leibowitz","orcid":"0000-0001-9440-7714","position":2,"is_corresponding":false},{"id":614928,"name":"William Austin Wyant","orcid":"0000-0002-2277-1549","position":3,"is_corresponding":false},{"id":1256576,"name":"Sabah Choudhury","orcid":"0009-0006-8172-9486","position":4,"is_corresponding":false},{"id":355472,"name":"Kihyun Park","orcid":"0000-0001-7841-624X","position":5,"is_corresponding":false},{"id":568325,"name":"Marianne Collard","orcid":"0000-0001-5267-8794","position":6,"is_corresponding":false},{"id":67,"name":"Philip A. Cole","orcid":"0000-0001-6873-7824","position":7,"is_corresponding":false},{"id":568328,"name":"Rhoda M. Alani","orcid":"0000-0003-2741-2665","position":8,"is_corresponding":false},{"id":816090,"name":"Aaron Waddell","orcid":"0000-0002-0605-3563","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:09:11.736910Z","pmid":"38469149","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":[]}