ACK1 is dispensable for development, skin tumor formation, and breast cancer cell proliferation.
FEBS Open Bio
; 11(6): 1579-1592, 2021 06.
Article
en En
| MEDLINE
| ID: mdl-33730447
Activated Cdc42-associated kinase 1 (ACK1), a widely expressed nonreceptor tyrosine kinase, is often amplified in cancer and has been shown to interact with Cell division cycle 42 (Cdc42), Epidermal growth factor receptor (EGFR), and several other cancer-relevant molecules, suggesting a possible role for ACK1 in development and tumor formation. To directly address this scenario, we generated mice lacking a functional ACK1 gene (ACK1 ko) using CRISPR genome editing. ACK1 ko mice developed normally, displayed no obvious defect in tissue maintenance, and were fertile. Primary ACK1-null keratinocytes showed normal phosphorylation of EGFR, but a tendency toward reduced activation of AKT serine/threonine kinase 1 (Akt) and Mitogen-activated protein kinase 1 (Erk). DMBA/TPA-induced skin tumor formation did not reveal significant differences between ACK1 ko and control mice. Deletion of the ACK1 gene in the breast cancer cell lines MDA-MB-231, 67NR, MCF7, 4T1, and T47D caused no differences in growth. Furthermore, EGF-induced phosphorylation kinetics of Erk, Akt, and p130Cas were not detectably altered in T47D cells by the loss of ACK1. Finally, loss of ACK1 in MDA-MB-231 and T47D breast cancer cells had a very limited or no effect on directed cell migration. These data do not support a major role for ACK1 in Cdc42 and EGFR signaling, development, or tumor formation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Tirosina Quinasas
/
Neoplasias de la Mama
Límite:
Animals
Idioma:
En
Revista:
FEBS Open Bio
Año:
2021
Tipo del documento:
Article
País de afiliación:
Dinamarca
Pais de publicación:
Reino Unido