{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T03:10:05Z","timestamp":1761102605912,"version":"build-2065373602"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/00473","PI21\/01047"],"award-info":[{"award-number":["PI18\/00473","PI21\/01047"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peritoneal metastasis of colorectal origin appears in ~10\u201315% of patients at the time of diagnosis and in 30\u201340% of cases with disease progression. Locoregional spread through the peritoneum is considered stage IVc and is associated with a poor prognosis. The development of a regional therapeutic strategy based on cytoreductive surgery, and hyperthermic intra\u2010abdominal chemotherapy has significantly altered the course of the disease. Although recent evidence supports the benefits of cytoreductive surgery, the benefits of hyperthermic intra\u2010abdominal chemotherapy are, however, still a matter of debate. Understanding the molecular alterations underlying the disease is crucial for developing new therapeutic strategies. Here, we evaluated the involvement in peritoneal dissemination of the oncogenic isoform of <jats:italic>TP73<\/jats:italic>, <jats:italic>\u0394Np73<\/jats:italic>, and its effector targets in <jats:italic>in vitro<\/jats:italic> and mouse models, and in 30 patients diagnosed with colorectal peritoneal metastasis. In an orthotopic mouse model, we observed that tumor cells overexpressing <jats:italic>\u0394Np73<\/jats:italic> present a higher avidity for the peritoneum and that extracellular vesicles secreted by <jats:italic>\u0394Np73<\/jats:italic>\u2010upregulating tumor cells enhance their dissemination. In addition, we identified that tumor cells overexpressing <jats:italic>\u0394Np73<\/jats:italic> present with dysregulation of genes associated with an epithelial\/mesothelial\u2010to\u2010mesenchymal transition (MMT) and that mesothelial cells exposed to the conditioned medium of tumor cells with upregulated <jats:italic>\u0394Np73<\/jats:italic> present a mesenchymal phenotype. Lastly, <jats:italic>\u0394Np73<\/jats:italic> and its effector target RNAs were dysregulated in our patient series, there were positive correlations between <jats:italic>\u0394Np73<\/jats:italic> and its effector targets, and <jats:italic>MSN<\/jats:italic> and <jats:italic>ITGB4<\/jats:italic> (<jats:italic>\u0394Np73<\/jats:italic> effectors) predicted patient survival. In conclusion, <jats:italic>\u0394Np73<\/jats:italic> and its effector targets are involved in the peritoneal dissemination of colorectal cancer and predict patient survival. The promotion of the EMT\/MMT and modulation of the adhesion capacity in colorectal cancer cells might be the mechanisms triggered by <jats:italic>\u0394Np73<\/jats:italic>. Remarkably, \u0394Np73 protein is a druggable protein and should be the focus of future studies. \u00a9 2024 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6286","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T05:31:21Z","timestamp":1713331881000},"page":"328-337","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp><i>\u0394Np73<\/i><\/scp> and its effector targets promote colorectal peritoneal carcinosis and predict survival"],"prefix":"10.1002","volume":"263","author":[{"given":"Daniel","family":"Pastor\u2010Morate","sequence":"first","affiliation":[{"name":"Department of Medicine, Faculty of Medicine \u201cAlberto Sols\u201d Biomedical Research Institute, CSIC\u2010UAM and IdiPAZ  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5540-3005","authenticated-orcid":false,"given":"Lidia","family":"Amigo\u2010Mor\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine \u201cAlberto Sols\u201d Biomedical Research Institute, CSIC\u2010UAM and IdiPAZ  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Garranzo\u2010Asensio","sequence":"additional","affiliation":[{"name":"Carlos III Health Institute Functional Research Unit into Chronic Diseases (UFIEC)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Rejas\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Carlos III Health Institute Functional Research Unit into Chronic Diseases (UFIEC)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Carnicero","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine \u201cAlberto Sols\u201d Biomedical Research Institute, CSIC\u2010UAM and IdiPAZ  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology La Paz University Hospital, IdiPAZ\u2010UAM  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Pedro","family":"P\u00e9rez\u2010Robledo","sequence":"additional","affiliation":[{"name":"Peritoneal Carcinosis Unit, Department of General and Gastrointestinal Surgery La Paz University Hospital, IdiPAZ\u2010UAM  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Barderas","sequence":"additional","affiliation":[{"name":"Carlos III Health Institute Functional Research Unit into Chronic Diseases (UFIEC)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Prieto\u2010Nieto","sequence":"additional","affiliation":[{"name":"Peritoneal Carcinosis Unit, Department of General and Gastrointestinal Surgery La Paz University Hospital, IdiPAZ\u2010UAM  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine \u201cAlberto Sols\u201d Biomedical Research Institute, CSIC\u2010UAM and IdiPAZ  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.10.003"},{"volume-title":"TNM classification of malignant 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