Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0029463 (
osteosarcoma
)
16,637
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 (Rab22a
1-38
) 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 Rab22a
1-38
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.
...
PMID:Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma. 3252 25
