DRG2 supports the growth of primary tumors and metastases of melanoma by enhancing VEGF-A expression.
FEBS J
; 287(10): 2070-2086, 2020 05.
Article
de En
| MEDLINE
| ID: mdl-31693298
ABSTRACT
Malignant metastatic melanoma (MM) is the most lethal of all skin cancers, but detailed mechanisms for regulation of melanoma metastasis are not fully understood. Here, we demonstrated that developmentally regulated GTP-binding protein 2 (DRG2) is required for the growth of primary tumors and for metastasis. DRG2 expression was significantly increased in MM compared with primary melanoma (PM) and dysplastic nevi. A correlation between DRG2 expression and poor disease-specific survival in melanoma patients was also identified. Furthermore, inhibition of DRG2 suppressed the binding of Hypoxia-inducible factor 1α to the VEGF-A promoter region, expression of vascular endothelial growth factor (VEGF)-A, and formation of endothelial cell tubes. In experimental mice, DRG2 depletion inhibited the growth of PM and lung metastases and increased survival. These results identify DRG2 as a critical regulator of VEGF-A expression and of growth of PMs and lung metastases.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protéines G
/
Facteur de croissance endothéliale vasculaire de type A
/
Sous-unité alpha du facteur-1 induit par l'hypoxie
/
Tumeurs du poumon
/
Mélanome
Type d'étude:
Prognostic_studies
Limites:
Adolescent
/
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
FEBS J
Sujet du journal:
BIOQUIMICA
Année:
2020
Type de document:
Article