PKCζ phosphorylates VASP to mediate chemotaxis in breast cancer cells.
Exp Cell Res
; 433(2): 113823, 2023 12 15.
Article
en En
| MEDLINE
| ID: mdl-37890607
ABSTRACT
Breast carcinoma (BC) is one of the most common malignant cancers in females, and metastasis remains the leading cause of death in these patients. Chemotaxis plays an important role in cancer cell metastasis and the mechanism of breast cancer chemotaxis has become a central issue in contemporary research. PKCζ, a member of the atypical PKC family, has been reported to be an essential component of the EGF-stimulated chemotactic signaling pathway. However, the molecular mechanism through which PKCζ regulates chemotaxis remains unclear. Here, we used a proteomic approach to identify PKCζ-interacting proteins in breast cancer cells and identified VASP as a potential binding partner. Intriguingly, stimulation with EGF enhanced this interaction and induced the translocalization of PKCζ and VASP to the cell membrane. Further experiments showed that PKCζ catalyzes the phosphorylation of VASP at Ser157, which is critical for the biological function of VASP in regulating chemotaxis and actin polymerization in breast cancer cells. Furthermore, in PKCζ knockdown BC cells, the enrichment of VASP at the leading edge was reduced, and its interaction with profilin1 was attenuated, thereby reducing the chemotaxis and overall motility of breast cancer cells after EGF treatment. In functional assays, PKCζ promoted chemotaxis and motility of BC cells through VASP. Our findings demonstrate that PKCζ, a new kinase of VASP, plays an important role in promoting breast cancer metastasis and provides a theoretical basis for expanding new approaches to tumor biotherapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína Quinasa C
/
Neoplasias de la Mama
/
Quimiotaxis
Límite:
Female
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Humans
Idioma:
En
Revista:
Exp Cell Res
Año:
2023
Tipo del documento:
Article