{"doi":"10.1016/j.canlet.2025.217695","title":"KAP1 promotes gastric adenocarcinoma progression by activating Hippo/YAP1 signaling via binding to HNRNPAB","abstract":"Gastric adenocarcinoma (GAC) remains a significant global health challenge, with over a million new cases annually. Peritoneal carcinomatosis (PC), detected in ∼20 % of cases at diagnosis and ∼45 % later, is uniformly fatal, with limited treatment options. This study investigated the role of KAP1 in GAC progression, focusing on its interaction with YAP1 and cancer stemness traits. Analysis of over 596 primary GACs and 72 PC samples revealed that high nuclear KAP1 expression correlates with poor prognosis. KAP1 knockdown reduced oncogenic activity and stemness traits in GAC cells. Mechanistically, KAP1 positively regulates YAP1 transcription by binding to its promoter and reducing H3K27ac levels. Mass spectrometry identified an interaction between KAP1 and HNRNPAB, further modulating YAP1 signaling. Expression of the KRAB domain of ZFP568 without its DNA-binding zinc fingers inhibited both KAP1 and YAP1 expression, significantly reducing colony formation and tumor growth in vivo. Additionally, emerging antisense oligonucleotides (ASOs) targeting KAP1 or YAP1 effectively suppressed mouse tumor progression. These findings establish KAP1 as a critical driver of tumor progression in GAC through YAP1 regulation and HNRNPAB interaction, highlighting its potential therapeutic target. This study advances our understanding and offers a preclinical framework to improve outcomes for GAC. • High nuclear KAP1 links to poor prognosis in gastric adenocarcinoma (GAC). • KAP1 knockdown reduces oncogenicity, stemness, and tumor growth in GAC cells. • KAP1 binds the YAP1 promoter, modulating H3K27ac and activating YAP1 signaling. • KAP1 interacts with HNRNPAB to enhance YAP1 transcription and oncogenic effects. • ASOs targeting KAP1 or YAP1 suppress tumor growth, offering new GAC therapies.","journal":"Cancer Letters","year":2025,"id":540818,"datarank":0.19157252982185072,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.02678068652163425,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.02678068652163425,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":719082,"name":"Yibo Fan","orcid":"0000-0001-7589-4158","position":1,"is_corresponding":false},{"id":991030,"name":"Gengyi Zou","orcid":"0000-0002-5399-8674","position":2,"is_corresponding":false},{"id":269007,"name":"Longfei Huo","orcid":null,"position":3,"is_corresponding":false},{"id":363056,"name":"Janani Kumar","orcid":null,"position":4,"is_corresponding":false},{"id":719080,"name":"Yuan Li","orcid":"0000-0002-5186-6360","position":5,"is_corresponding":false},{"id":1034912,"name":"Ruiping Wang","orcid":"0000-0002-1726-7241","position":6,"is_corresponding":false},{"id":554755,"name":"Enyu Dai","orcid":"0000-0001-5836-0277","position":7,"is_corresponding":false},{"id":342227,"name":"Jiankang Jin","orcid":"0000-0001-9864-9817","position":8,"is_corresponding":false},{"id":342226,"name":"Ailing W. 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