{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:48:26Z","timestamp":1789426106874,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2019-104734RB-I00"],"award-info":[{"award-number":["PID2019-104734RB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["SAF2016-80157-R"],"award-info":[{"award-number":["SAF2016-80157-R"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["grupos estables AECC"],"award-info":[{"award-number":["grupos estables AECC"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>TGF-\u03b2 has a dichotomous function, acting as tumor suppressor in premalignant cells but as a tumor promoter for cancerous cells. These contradictory functions of TGF-\u03b2 are caused by different cellular contexts, including both intracellular and environmental determinants. The TGF-\u03b2\/SMAD and the PI3K\/PTEN\/AKT signal transduction pathways have an important role in the regulation of epithelial cell homeostasis and perturbations in either of these two pathways\u2019 contributions to endometrial carcinogenesis. We have previously demonstrated that both PTEN and SMAD2\/3 display tumor-suppressive functions in the endometrium, and genetic ablation of either gene results in sustained activation of PI3K\/AKT signaling that suppresses TGF-\u03b2-induced apoptosis and enhances cell proliferation of mouse endometrial cells. However, the molecular and cellular effects of PTEN deficiency on TGF-\u03b2\/SMAD2\/3 signaling remain controversial. Here, using an in vitro and in vivo model of endometrial carcinogenesis, we have demonstrated that loss of PTEN leads to a constitutive SMAD2\/3 nuclear translocation. To ascertain the function of nuclear SMAD2\/3 downstream of PTEN deficiency, we analyzed the effects of double deletion PTEN and SMAD2\/3 in mouse endometrial organoids. Double PTEN\/SMAD2\/3 ablation results in a further increase of cell proliferation and enlarged endometrial organoids compared to those harboring single PTEN, suggesting that nuclear translocation of SMAD2\/3 constrains tumorigenesis induced by PTEN deficiency.<\/jats:p>","DOI":"10.3390\/cancers13194990","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T09:24:04Z","timestamp":1633598644000},"page":"4990","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Endometrial PTEN Deficiency Leads to SMAD2\/3 Nuclear Translocation"],"prefix":"10.3390","volume":"13","author":[{"given":"N\u00faria","family":"Eritja","sequence":"first","affiliation":[{"name":"Oncologic Pathology Group, Departament de Ci\u00e8ncies M\u00e8diques B\u00e0siques, Institut de Recerca Biom\u00e8dica de Lleida, IRBLleida, Universitat de Lleida, Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer CIBERONC, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Navaridas","sequence":"additional","affiliation":[{"name":"Oncologic Pathology Group, Departament de Ci\u00e8ncies M\u00e8diques B\u00e0siques, Institut de Recerca Biom\u00e8dica de Lleida, IRBLleida, Universitat de Lleida, Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer CIBERONC, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7137-0736","authenticated-orcid":false,"given":"Anna","family":"Ruiz-Mitjana","sequence":"additional","affiliation":[{"name":"Oncologic Pathology Group, Departament de Ci\u00e8ncies M\u00e8diques B\u00e0siques, Institut de Recerca Biom\u00e8dica de Lleida, IRBLleida, Universitat de Lleida, Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer CIBERONC, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4154-6061","authenticated-orcid":false,"given":"Maria","family":"Vidal-Saban\u00e9s","sequence":"additional","affiliation":[{"name":"Oncologic Pathology Group, Departament de Ci\u00e8ncies M\u00e8diques B\u00e0siques, Institut de Recerca Biom\u00e8dica de Lleida, IRBLleida, Universitat de Lleida, Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer CIBERONC, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"Egea","sequence":"additional","affiliation":[{"name":"Molecular Developmental Neurobiology Group, Departament de Ci\u00e8ncies M\u00e8diques B\u00e0siques, Institut de Recerca Biom\u00e8dica de Lleida, IRBLleida, Universitat de Lleida, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Encinas","sequence":"additional","affiliation":[{"name":"Developmental and Oncogenic Signalling Group, Departament de Medicina Experimental, Institut de Recerca Biom\u00e8dica de Lleida, IRBLleida, Universitat de Lleida, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Matias-Guiu","sequence":"additional","affiliation":[{"name":"Oncologic Pathology Group, Departament de Ci\u00e8ncies M\u00e8diques B\u00e0siques, Institut de Recerca Biom\u00e8dica de Lleida, IRBLleida, Universitat de Lleida, Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer CIBERONC, 25198 Lleida, Spain"},{"name":"Department of Pathology, Hospital Universitari de Bellvitge, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1921-0449","authenticated-orcid":false,"given":"Xavier","family":"Dolcet","sequence":"additional","affiliation":[{"name":"Oncologic Pathology Group, Departament de Ci\u00e8ncies M\u00e8diques B\u00e0siques, Institut de Recerca Biom\u00e8dica de Lleida, IRBLleida, Universitat de Lleida, Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer CIBERONC, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/nrm3434","article-title":"TGF\u03b2 signalling in context","volume":"13","year":"2012","journal-title":"Nat. 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