{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:50:19Z","timestamp":1792122619599,"version":"4.4.0"},"reference-count":65,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre","doi-asserted-by":"crossref","award":["2021\/05\/X\/NZ3\/00210"],"award-info":[{"award-number":["2021\/05\/X\/NZ3\/00210"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical University of Lodz Rector\u2019s Research","award":["503\/1-156-01\/503-99-016"],"award-info":[{"award-number":["503\/1-156-01\/503-99-016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Targeted therapies, including treatment with inhibitors of BRAFV600 and MEK kinases, have improved outcomes in advanced melanoma. However, most patients relapse due to acquired resistance, underscoring the need for new drug targets. This study evaluated PRI-724, a CBP\/\u03b2-catenin inhibitor, in patient-derived drug-na\u00efve melanoma cells and their trametinib- or vemurafenib-resistant counterparts. While PRI-724 has demonstrated efficacy in preclinical models and clinical trials in different cancer types, its potential in melanoma has not been previously assessed. We found that treatment with PRI-724 downregulated survivin and other CBP\/\u03b2-catenin target proteins, reduced invasiveness, and induced apoptosis in drug-na\u00efve and trametinib- and vemurafenib-resistant cells. Trametinib-resistant melanoma cells showed the greatest sensitivity to PRI-724, indicating that CBP\/\u03b2-catenin transcriptional activity may represent a new therapeutic vulnerability. Transcriptomic and immunoblotting analyses revealed the highest survivin levels in vemurafenib-resistant cells, which may underlie their reduced responsiveness to PRI-724. Bioinformatic analyses (TCGA and GSE50509) confirmed that a high survivin level predicts poor prognosis and reduced response to treatment. The results of the study point to the potential of PRI-724 as a chemotherapeutic agent for the treatment of melanoma. Its efficacy might depend on CBP\/\u03b2-catenin transcriptional activity in melanoma cells, and further evaluation of this signaling with survivin as a biomarker is therefore warranted.<\/jats:p>","DOI":"10.3390\/cells14211710","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"1710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cellular and Molecular Effects of Targeting the CBP\/\u03b2-Catenin Interaction with PRI-724 in Melanoma Cells, Drug-Na\u00efve and Resistant to Inhibitors of BRAFV600 and MEK1\/2"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6159-4194","authenticated-orcid":false,"given":"Anna","family":"Gajos-Michniewicz","sequence":"first","affiliation":[{"name":"Department of Molecular Biology of Cancer, Medical University of Lodz, 6\/8 Mazowiecka Street, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2251-8647","authenticated-orcid":false,"given":"Michal","family":"Wozniak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology of Cancer, Medical University of Lodz, 6\/8 Mazowiecka Street, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7290-1647","authenticated-orcid":false,"given":"Katarzyna Anna","family":"Kluszczynska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology of Cancer, Medical University of Lodz, 6\/8 Mazowiecka Street, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8279-4742","authenticated-orcid":false,"given":"Malgorzata","family":"Czyz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology of Cancer, Medical University of Lodz, 6\/8 Mazowiecka Street, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ernst, M., and Giubellino, A. 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