Tissue inhibitor of metalloproteinase-1 promotes cell proliferation through YAP/TAZ activation in cancer.
Oncogene
; 37(2): 263-270, 2018 01 11.
Article
en En
| MEDLINE
| ID: mdl-28925394
ABSTRACT
Tissue inhibitor of metalloproteinase-1 (TIMP-1), a member of the TIMP family (TIMP-1 to 4), is highly expressed in various types of cancer and forms a complex with its receptor CD63 and Integrin ß1. However, the precise oncogenic mechanism of TIMP-1 remains unclear. Yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) are transcription co-activators enhancing the transcription of specific genes related to cell proliferation. But the mechanism of aberrant YAP/TAZ activation in cancer is not fully understood. Here, we showed that TIMP-1 activates YAP/TAZ as novel downstream targets to promote cell proliferation. The TIMP-1-CD63-Integrin ß1 axis activates Src and promotes RhoA-mediated F-actin assembly, leading to LATS1/2 inactivation. This results in under-phosphorylation, protein stabilization and nuclear translocation of YAP/TAZ (YAP/TAZ activation); CTGF production; and cell proliferation. Furthermore, the TIMP-1-YAP/TAZ axis is aberrantly activated in various types of cancer cells or tissues. TIMP-1 knockdown inhibits cell proliferation through YAP/TAZ inactivation in cancer cells. This study found that TIMP-1 accelerates cell proliferation through YAP/TAZ activation in cancer, and suggests the TIMP-1-YAP/TAZ axis may be a novel potential drug target for cancer patients.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Inhibidor Tisular de Metaloproteinasa-1
/
Péptidos y Proteínas de Señalización Intracelular
/
Proteínas Adaptadoras Transductoras de Señales
/
Proliferación Celular
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón