Cover Image

Resistance to mesenchymal reprogramming sustains clonal propagation in metastatic breast cancer

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 m...

Full description

Saved in:
Bibliographic Details
Main Authors: Saini, Massimo (Author) , Schmidleitner, Laura (Author) , Domínguez Moreno, Helena (Author) , Donato, Elisa (Author) , Falcone, Mattia (Author) , Bartsch, Johanna M. (Author) , Klein, Corinna (Author) , Vogel, Vanessa (Author) , Würth, Roberto (Author) , Pfarr, Nicole (Author) , Espinet, Elisa (Author) , Lehmann, Mareike (Author) , Königshoff, Melanie (Author) , Reitberger, Manuel (Author) , Haas, Simon (Author) , Graf, Elisabeth (Author) , Schwarzmayr, Thomas (Author) , Strom, Tim-Matthias (Author) , Spaich, Saskia (Author) , Sütterlin, Marc (Author) , Schneeweiss, Andreas (Author) , Weichert, Wilko (Author) , Schotta, Gunnar (Author) , Reichert, Maximilian (Author) , Aceto, Nicola (Author) , Sprick, Martin (Author) , Trumpp, Andreas (Author) , Scheel, Christina H. (Author)
Format: Article (Journal)
Language:English
Published: 30 May 2023
In: Cell reports
Year: 2023, Volume: 42, Issue: 6
ISSN:2211-1247
DOI:10.1016/j.celrep.2023.112533
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.celrep.2023.112533
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124723005442
Get full text
Author Notes:Massimo Saini, Laura Schmidleitner, Helena Domínguez Moreno, Elisa Donato, Mattia Falcone, Johanna M. Bartsch, Corinna Klein, Vanessa Vogel, Roberto Würth, Nicole Pfarr, Elisa Espinet, Mareike Lehmann, Melanie Königshoff, Manuel Reitberger, Simon Haas, Elisabeth Graf, Thomas Schwarzmayr, Tim-Matthias Strom, Saskia Spaich, Marc Sütterlin, Andreas Schneeweiss, Wilko Weichert, Gunnar Schotta, Maximilian Reichert, Nicola Aceto, Martin R. Sprick, Andreas Trumpp, Christina H. Scheel
Description
Summary: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.
Item Description:Online verfügbar 30 Mai 2023, Version des Artikels 27 Juni 2023
Gesehen am 27.06.2024
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2023.112533

Similar Items