Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA.
Cell Rep
; 42(4): 112338, 2023 04 25.
Article
en En
| MEDLINE
| ID: mdl-37027295
ABSTRACT
During intravasation, cancer cells cross the endothelial barrier and enter the circulation. Extracellular matrix stiffening has been correlated with tumor metastatic potential; however, little is known about the effects of matrix stiffness on intravasation. Here, we utilize in vitro systems, a mouse model, specimens from patients with breast cancer, and RNA expression profiles from The Cancer Genome Atlas Program (TCGA) to investigate the molecular mechanism by which matrix stiffening promotes tumor cell intravasation. Our data show that heightened matrix stiffness increases MENA expression, which promotes contractility and intravasation through focal adhesion kinase activity. Further, matrix stiffening decreases epithelial splicing regulatory protein 1 (ESRP1) expression, which triggers alternative splicing of MENA, decreases the expression of MENA11a, and enhances contractility and intravasation. Altogether, our data indicate that matrix stiffness regulates tumor cell intravasation through enhanced expression and ESRP1-mediated alternative splicing of MENA, providing a mechanism by which matrix stiffness regulates tumor cell intravasation.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Empalme Alternativo
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos