Distinct contributions of partial and full EMT to breast cancer malignancy.
Animals
Antineoplastic Agents
/ pharmacology
Apoptosis
Biomarkers, Tumor
/ genetics
Breast Neoplasms
/ drug therapy
Cell Movement
Cell Proliferation
Drug Resistance, Neoplasm
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ drug therapy
Mice
Mice, Inbred NOD
Mice, SCID
Neoplasm Invasiveness
Sequence Analysis, RNA
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
EMT
EMT continuum
breast cancer
collective cell migration
dual recombinase
lineage tracing
metastasis
mouse models
therapy resistance
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
06 12 2021
06 12 2021
Historique:
received:
29
03
2021
revised:
13
09
2021
accepted:
05
11
2021
pubmed:
1
12
2021
medline:
4
1
2022
entrez:
30
11
2021
Statut:
ppublish
Résumé
Epithelial-mesenchymal transition (EMT) is a transient, reversible process of cell de-differentiation where cancer cells transit between various stages of an EMT continuum, including epithelial, partial EMT, and mesenchymal cell states. We have employed Tamoxifen-inducible dual recombinase lineage tracing systems combined with live imaging and 5-cell RNA sequencing to track cancer cells undergoing partial or full EMT in the MMTV-PyMT mouse model of metastatic breast cancer. In primary tumors, cancer cells infrequently undergo EMT and mostly transition between epithelial and partial EMT states but rarely reach full EMT. Cells undergoing partial EMT contribute to lung metastasis and chemoresistance, whereas full EMT cells mostly retain a mesenchymal phenotype and fail to colonize the lungs. However, full EMT cancer cells are enriched in recurrent tumors upon chemotherapy. Hence, cancer cells in various stages of the EMT continuum differentially contribute to hallmarks of breast cancer malignancy, such as tumor invasion, metastasis, and chemoresistance.
Identifiants
pubmed: 34847378
pii: S1534-5807(21)00891-1
doi: 10.1016/j.devcel.2021.11.006
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3203-3221.e11Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.