Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence.
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Embargo End Date
ICR Authors
Authors
Aouad, P
Zhang, Y
De Martino, F
Stibolt, C
Ali, S
Ambrosini, G
Mani, SA
Maggs, K
Quinn, HM
Sflomos, G
Brisken, C
Zhang, Y
De Martino, F
Stibolt, C
Ali, S
Ambrosini, G
Mani, SA
Maggs, K
Quinn, HM
Sflomos, G
Brisken, C
Document Type
Journal Article
Date
2022-08-25
Date Accepted
2022-08-02
Abstract
More than 70% of human breast cancers (BCs) are estrogen receptor α-positive (ER+). A clinical challenge of ER+ BC is that they can recur decades after initial treatments. Mechanisms governing latent disease remain elusive due to lack of adequate in vivo models. We compare intraductal xenografts of ER+ and triple-negative (TN) BC cells and demonstrate that disseminated TNBC cells proliferate similarly as TNBC cells at the primary site whereas disseminated ER+ BC cells proliferate slower, they decrease CDH1 and increase ZEB1,2 expressions, and exhibit characteristics of epithelial-mesenchymal plasticity (EMP) and dormancy. Forced E-cadherin expression overcomes ER+ BC dormancy. Cytokine signalings are enriched in more active versus inactive disseminated tumour cells, suggesting microenvironmental triggers for awakening. We conclude that intraductal xenografts model ER + BC dormancy and reveal that EMP is essential for the generation of a dormant cell state and that targeting exit from EMP has therapeutic potential.
Citation
Nature Communications, 2022, 13 (1), pp. 4975 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
2041-1723
2041-1723
Collections
Research Team
Endocrine control mechans