A Cdh3-ß-catenin-laminin signaling axis in a subset of breast tumor leader cells control leader cell polarization and directional collective migration.
Dev Cell
; 58(1): 34-50.e9, 2023 01 09.
Article
de En
| MEDLINE
| ID: mdl-36626870
ABSTRACT
Carcinoma dissemination can occur when heterogeneous tumor and tumor-stromal cell clusters migrate together via collective migration. Cells at the front lead and direct collective migration, yet how these leader cells form and direct migration are not fully appreciated. From live videos of primary mouse and human breast tumor organoids in a 3D microfluidic system mimicking native breast tumor microenvironment, we developed 3D computational models, which hypothesize that leader cells need to generate high protrusive forces and overcome extracellular matrix (ECM) resistance at the leading edge. From single-cell sequencing analyses, we find that leader cells are heterogeneous and identify and isolate a keratin 14- and cadherin-3-positive subpopulation sufficient to lead collective migration. Cdh3 controls leader cell protrusion dynamics through local production of laminin, which is required for integrin/focal adhesion function. Our findings highlight how a subset of leader cells interact with the microenvironment to direct collective migration.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du sein
/
Tumeurs mammaires de l'animal
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Female
/
Humans
Langue:
En
Journal:
Dev Cell
Sujet du journal:
EMBRIOLOGIA
Année:
2023
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique