@misc{10481/93945, year = {2024}, month = {8}, url = {https://hdl.handle.net/10481/93945}, abstract = {Emerging studies support that the polycomb repressive complex 2 (PRC2) regulates phenotypic changes of carcinoma cells by modulating their shifts among metastable states within the epithelial and mesenchymal spectrum. This new role of PRC2 in cancer has been recently proposed to stem from the ability of its catalytic subunit EZH2 to bind and modulate the transcription of mesenchymal genes during epithelial-mesenchymal transition (EMT) in lung cancer cells. Here, we asked whether this mechanism is conserved in other types of carcinomas. By combining TGF-β-mediated reversible induction of epithelial to mesenchymal transition and inhibition of EZH2 methyltransferase activity, we demonstrate that EZH2 represses a large set of mesenchymal genes and favours the residence of breast cancer cells towards the more epithelial spectrum during EMT. In agreement, analysis of human patient samples supports that EZH2 is required to efficiently repress mesenchymal genes in breast cancer tumours. Our results indicate that PRC2 operates through similar mechanisms in breast and lung cancer cells. We propose that PRC2-mediated direct transcriptional modulation of the mesenchymal gene expression programme is a conserved molecular mechanism underlying cell dissemination across human carcinomas.}, organization = {Instituto de Salud Carlos III under the European funds of the Recovery, Transformation and Resilience Plan, with file code IHRC22/00007, by virtue of Resolution of the Directorate of the Instituto de Salud Carlos III, O.A., M.P. of December 22, 2022, granting grants Seal of Excellence ISCIII-HEALTH, and Financed by the European Union—NextGenerationEU}, organization = {Spanish Ministry of Science and Innovation (EUR2021-122005, PID2022-137060NBI00)}, organization = {Andalusian regional government (PIER-0211-2019, PY20_00681)}, organization = {University of Granada (A-BIO-6-UGR20)}, organization = {“Plan-Propio UGR” grant (A.CTS.264.UGR23)}, organization = {“Plan-Propio UGR” grant (C-CTS-274-UGR23)}, publisher = {Springer Nature}, title = {EZH2 represses mesenchymal genes and upholds the epithelial state of breast carcinoma cells}, doi = {10.1038/s41419-024-07011-y}, author = {Gallardo, Amador and López Onieva, Lourdes and Belmonte Reche, Efres and Fernández Rengel, Iván and Serrano Prados, Andrea and Molina, Aldara and Sánchez Pozo, Antonio and Landeira Frías, David Marcos}, }