{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:50:58Z","timestamp":1775591458062,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:00:00Z","timestamp":1616716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["por-journal.com"],"crossmark-restriction":true},"short-container-title":["Pathol. Oncol. Res."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Uterine carcinosarcoma (UCS) is a rare but highly aggressive malignancy with biphasic growth pattern. This morphology can be attributed to epithelial-mesenchymal transition (EMT) that often associates with tumor invasion and metastasis. Accordingly, we analyzed a novel patient-derived preclinical model to explore whether EMT is a potential target in UCS.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A novel UCS cell line (PF338) was established from the malignant pleural effusion of a 59-year-old patient at time of disease progression. Immunohistochemistry was performed in primary and metastatic tumor lesions. Oncogenic mutations were identified by next-generation sequencing. Viability assays and cell cycle analyses were used to test <jats:italic>in vitro<\/jats:italic> sensitivity to different standard and novel treatments. E-cadherin, \u03b2-catenin and pSMAD2 expressions were measured by immunoblot.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Whereas immunohistochemistry of the metastatic tumor showed a predominantly sarcomatous vimentin positive tumor that has lost E-cadherin expression, PF338 cells demonstrated biphasic growth and carried mutations in <jats:italic>KRAS<\/jats:italic>, <jats:italic>PIK3CA<\/jats:italic>, <jats:italic>PTEN<\/jats:italic> and <jats:italic>ARID1A<\/jats:italic>. PF338 tumor cells were resistant to MEK- and TGF-\u03b2 signaling-inhibition but sensitive to PIK3CA- and PARP-inhibition and first-line chemotherapeutics. Strikingly, histone deacetylase (HDAC) inhibition markedly reduced cell viability by inducing a dose-dependent G0\/1 arrest and led to mesenchymal-epithelial transition as evidenced by morphological change and increased E-cadherin and \u03b2-catenin expression.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Our data suggest that HDAC inhibition is effective in a novel UCS cell line by interfering with both viability and differentiation. These findings emphasize the dynamic manner of EMT\/MET and epigenetics and the importance of molecular profiling to pave the way for novel therapies in UCS.<\/jats:p>","DOI":"10.3389\/pore.2021.636088","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T04:11:35Z","timestamp":1616731895000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["HDAC Inhibition Induces Cell Cycle Arrest and Mesenchymal-Epithelial Transition in a Novel Pleural-Effusion Derived Uterine Carcinosarcoma Cell 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