{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:19:59Z","timestamp":1792120799718,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","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":["LABAE19004LLOB"],"award-info":[{"award-number":["LABAE19004LLOB"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP17\/00063"],"award-info":[{"award-number":["CP17\/00063"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/00795"],"award-info":[{"award-number":["PI18\/00795"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006280","name":"Ministerio de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["MS17\/00063"],"award-info":[{"award-number":["MS17\/00063"]}],"id":[{"id":"10.13039\/501100006280","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["PZ00P3_168077"],"award-info":[{"award-number":["PZ00P3_168077"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>\n                    Uterine serous carcinoma (USC) is an aggressive form of endometrial cancer (EC), characterized by its high propensity for metastases. In fact, while endometrioid endometrial carcinoma (EEC), which accounts for 85% of EC, presents a good prognosis, USC is the most frequently fatal. Herein, we used for the first time a peptide\u2010based tyrosine\u2010kinase\u2010activity profiling approach to quantify the changes in tyrosine kinase activation between USC and EEC. Among the tyrosine kinases highly activated in USC, we identified focal adhesion kinase (FAK). We conducted mechanistic studies using cellular models. In a USC cell line, targeting FAK either by inhibitors PF\u2010573228 and defactinib (VS\u20106063) or by gene silencing limits 3D cell growth and reduces cell migration. Moreover, results from our studies suggest that oxidative stress is increased in USC tumors compared to EEC ones. Reactive oxygen species (ROS) induce tyrosine phosphorylation of FAK and a concomitant tyrosine phosphorylation of paxillin, a mediator of FAK signal transduction. Mechanistically, by tracking hundreds of individual cells per condition, we show that ROS increased cell distance and migration velocity, highlighting the role of ROS\u2010FAK\u2010PAX signaling in cell migration. Both defactinib and ROS scavenger N\u2010acetylcysteine (NAC) revert this effect, pointing toward ROS as potential culprits for the increase in USC cell motility. A proof of concept of the role of FAK in controlling cell growth was obtained in\n                    <jats:italic>in\u2009vivo<\/jats:italic>\n                    experiments using cancer\u2010tissue\u2010originated spheroids (CTOS) and a patient\u2010derived orthotopic xenograft model (orthoxenograft\/PDOX). Defactinib reduces cell proliferation and protein oxidation, supporting a pro\u2010tumoral antioxidant role of FAK, whereas antioxidant NAC reverts FAK inhibitor effects. Overall, our data points to ROS\u2010mediated FAK activation in USC as being responsible for the poor prognosis of this tumor type and emphasize the potential of FAK inhibition for USC treatment.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13346","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T09:41:50Z","timestamp":1669023710000},"page":"98-118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Oxidative stress\u2010induced\n                    <scp>FAK<\/scp>\n                    activation contributes to uterine serous carcinoma aggressiveness"],"prefix":"10.1002","volume":"17","author":[{"given":"Isabel C.","family":"Lopez\u2010Mejia","sequence":"first","affiliation":[{"name":"Center for Integrative Genomics University of Lausanne  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Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova (HUAV), IRBLleida University of Lleida  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Velasco","sequence":"additional","affiliation":[{"name":"Pathology Group, Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova (HUAV), IRBLleida University of Lleida  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Castell\u00e0","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Hospital Universitari Arnau de Vilanova, IRB\u2010Lleida University of Lleida  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs","family":"Panosa","sequence":"additional","affiliation":[{"name":"Flow Cytometry and Confocal Microscopy Unit, IRBLleida University of Lleida  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