Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence.
Date
2022-08-25ICR Author
Author
Aouad, P
Zhang, Y
De Martino, F
Stibolt, C
Ali, S
Ambrosini, G
Mani, SA
Maggs, K
Quinn, HM
Sflomos, G
Brisken, C
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Breast Neoplasms
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Female
Humans
Receptors, Estrogen
Triple Negative Breast Neoplasms
Research team
Endocrine control mechans
Language
eng
Date accepted
2022-08-02
License start date
2022-08-25
Citation
Nature Communications, 2022, 13 (1), pp. 4975 -
Publisher
NATURE PORTFOLIO