Subpopulation commensalism promotes Rac1-dependent invasion of single cells via laminin-332.
J Cell Biol
; 223(6)2024 06 03.
Article
en En
| MEDLINE
| ID: mdl-38551497
ABSTRACT
Phenotypic heterogeneity poses a significant hurdle for cancer treatment but is under-characterized in the context of tumor invasion. Amidst the range of phenotypic heterogeneity across solid tumor types, collectively invading cells and single cells have been extensively characterized as independent modes of invasion, but their intercellular interactions have rarely been explored. Here, we isolated collectively invading cells and single cells from the heterogeneous 4T1 cell line and observed extensive transcriptional and epigenetic diversity across these subpopulations. By integrating these datasets, we identified laminin-332 as a protein complex exclusively secreted by collectively invading cells. Live-cell imaging revealed that laminin-332 derived from collectively invading cells increased the velocity and directionality of single cells. Despite collectively invading and single cells having similar expression of the integrin α6ß4 dimer, single cells demonstrated higher Rac1 activation upon laminin-332 binding to integrin α6ß4. This mechanism suggests a novel commensal relationship between collectively invading and single cells, wherein collectively invading cells promote the invasive potential of single cells through a laminin-332/Rac1 axis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Laminina
/
Proteína de Unión al GTP rac1
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Biol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos