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http://hdl.handle.net/2445/205421
Title: | Resistance to mesenchymal reprogramming sustains clonal propagation in metastatic breast cancer |
Author: | Saini, Massimo Schmidleitner, Laura Domínguez Moreno, Helena Donato, Elisa Falcone, Mattia Bartsch, Johanna M. Klein, Corinna Vogel, Vanessa Würth, Roberto Pfarr, Nicole Espinet, Elisa Lehmann, Mareike Königshoff, Melanie Reitberger, Manuel Haas, Simon Graf, Elisabeth Schwarzmayr, Thomas Strom, Tim-Matthias Spaich, Saskia Sütterlin, Marc Schneeweiss, Andreas Weichert, Wilko Schotta, Gunnar Reichert, Maximilian Aceto, Nicola Sprick, Martin R. Trumpp, Andreas Scheel, Christina H. |
Keywords: | Càncer de mama Metàstasi Breast cancer Metastasis |
Issue Date: | 1-Jun-2023 |
Publisher: | Elsevier BV Cell Press |
Abstract: | The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo. Strikingly, progressively decreasing epithelial cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, we find that persistent EPCAM expression marks epithelial clones that resist EMT induction and propagate competitively. In contrast, loss of EPCAM defines clones arrested in a mesenchymal state, with concomitant suppression of tumorigenicity and metastatic potential. This dichotomy results from distinct clonal trajectories impacting global epigenetic programs that are determined by the interplay between human ZEB1 and its target GRHL2. Collectively, our results indicate that susceptibility to irreversible EMT restrains clonal propagation, whereas resistance to mesenchymal reprogramming sustains disease spread in multiple models of human metastatic breast cancer, including patient-derived cells in vivo. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2023.112533 |
It is part of: | Cell Reports, 2023, vol. 42, num. 6 |
URI: | http://hdl.handle.net/2445/205421 |
Related resource: | https://doi.org/10.1016/j.celrep.2023.112533 |
ISSN: | 2211-1247 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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