Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma.
Nat Cell Biol
; 22(7): 868-881, 2020 07.
Article
en En
| MEDLINE
| ID: mdl-32483387
ABSTRACT
Osteosarcoma is a type of aggressive malignant bone tumour that frequently metastasizes to lungs, resulting in poor prognosis. However, the molecular mechanisms of lung metastasis of osteosarcoma remain poorly understood. Here we identify exon-intron fusion genes in osteosarcoma cell lines and tissues. These fusion genes are derived from chromosomal translocations that juxtapose the coding region for amino acids 1-38 of Rab22a (Rab22a1-38) with multiple inverted introns and untranslated regions of chromosome 20. The resulting translation products, designated Rab22a-NeoFs, acquire the ability to drive lung metastasis of osteosarcoma. The Rab22a1-38 moiety governs the function of Rab22a-NeoFs by binding to SmgGDS-607, a GTP-GDP exchange factor of RhoA. This association facilitates the release of GTP-bound RhoA from SmgGDS-607, which induces increased activity of RhoA and promotes metastasis. Disrupting the interaction between Rab22a-NeoF1 and SmgGDS-607 with a synthetic peptide prevents lung metastasis in an orthotopic model of osteosarcoma. Our findings may provide a promising strategy for a subset of osteosarcoma patients with lung metastases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Translocación Genética
/
Neoplasias Óseas
/
Biomarcadores de Tumor
/
Osteosarcoma
/
Proteínas de Unión al GTP rab
/
Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Cell Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
China