{"doi":"10.18632/oncotarget.27700","title":"Targeting 14-3-3ε-CDC25A interactions to trigger apoptotic cell death in skin cancer","abstract":"// Thomas R. Holmes 1 , 2 , Jenan Al-Matouq 1 , 3 , Matti Holmes 1 , Lauren Nicola 1 , Justin C. Rudd 1 , Sándor Lovas 1 and Laura A. Hansen 1 1 Creighton University School of Medicine, Department of Biomedical Sciences, Omaha, NE, USA 2 Current Address: Northwestern University, Chicago, IL, USA 3 Current Address: Mohammed Al-mana College for Medical Science, Dammam, Kingdom of Saudi Arabia Correspondence to: Sándor Lovas, email: sandorlovas@creighton.edu Laura A. Hansen, email: LHansen@creighton.edu Keywords: skin cancer; squamous cell carcinoma; CDC25A; 14-3-3ε; apoptosis Received: July 17, 2019     Accepted: July 21, 2020     Published: September 01, 2020 ABSTRACT Non-melanoma skin cancer is the most common form of cancer worldwide. We previously documented an anti-apoptotic role for CDC25A in cutaneous squamous cell carcinoma (SCC), an activity dependent on its association with 14-3-3 proteins. We hypothesized that targeting CDC25A-14-3-3ε interactions may be an effective strategy for inducing skin cancer cell apoptosis. Co-immunoprecipitation revealed that CDC25A associated with 14-3-3ε, 14-3-3γ and 14-3-3ζ in SCC cells but not normal keratinocytes. 14-3-3ε and CDC25A activated Akt/BAD/Survivin pro-survival signaling. To target the interaction of 14-3-3ε with CDC25A for cancer therapy, we developed two novel phospho-peptides, pS and pT, corresponding to each of the 14-3-3 binding sites of CDC25A, to specifically interfere with 14-3-3ε binding to CDC25A. Peptides pT (IC 50 = 22.1 μM), and pS (IC 50 = 29 μM) induced SCC cell death and blocked 14-3-3ε binding to CDC25A. pS or pT treatment of SCC xenografts increased apoptotic cell death and decreased pro-survival P-Akt (S473) and Survivin, demonstrating the effectiveness of the peptides in vivo . These findings lay a framework for the further development of peptides to target 14-3-3ε-CDC25A interactions for skin cancer treatment.","journal":"Oncotarget","year":2020,"id":72161,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":380789,"name":"Jenan Al‐Matouq","orcid":"0000-0001-5382-508X","position":1,"is_corresponding":false},{"id":370612,"name":"Matti Holmes","orcid":null,"position":2,"is_corresponding":false},{"id":370615,"name":"Lauren Nicola","orcid":null,"position":3,"is_corresponding":false},{"id":370613,"name":"Justin C. Rudd","orcid":null,"position":4,"is_corresponding":false},{"id":369893,"name":"Sándor Lovas","orcid":"0000-0002-5089-5186","position":5,"is_corresponding":false},{"id":369894,"name":"Laura A. Hansen","orcid":"0000-0003-3436-8412","position":6,"is_corresponding":false},{"id":369891,"name":"Thomas R. Holmes","orcid":"0000-0003-0054-3999","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T21:44:45.622639Z","pmid":"32934772","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":[]}