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Article: Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma

TitleChromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma
Authors
KeywordsGuanine Nucleotide Dissociation Inhibitors
Guanosine Triphosphate
GTPase-Activating Proteins
Issue Date2020
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturecellbiology
Citation
Nature Cell Biology, 2020, v. 22 n. 7, p. 868-881 How to Cite?
AbstractOsteosarcoma 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.
Persistent Identifierhttp://hdl.handle.net/10722/284816
ISSN
2019 Impact Factor: 20.042
2015 SCImago Journal Rankings: 14.131
ISI Accession Number ID
Errata

 

DC FieldValueLanguage
dc.contributor.authorLiao, D-
dc.contributor.authorZhong, L-
dc.contributor.authorYin, J-
dc.contributor.authorZeng, C-
dc.contributor.authorWang, X-
dc.contributor.authorHuang, X-
dc.contributor.authorZhang, H-
dc.contributor.authorZhang, R-
dc.contributor.authorGuan, XY-
dc.contributor.authorShuai, X-
dc.contributor.authorSui, J-
dc.contributor.authorGao, S-
dc.contributor.authorDeng, W-
dc.contributor.authorZeng, YX-
dc.contributor.authorShen, JN-
dc.contributor.authorChen, J-
dc.contributor.authorChen, J-
dc.contributor.authorKang, T-
dc.date.accessioned2020-08-07T09:03:00Z-
dc.date.available2020-08-07T09:03:00Z-
dc.date.issued2020-
dc.identifier.citationNature Cell Biology, 2020, v. 22 n. 7, p. 868-881-
dc.identifier.issn1465-7392-
dc.identifier.urihttp://hdl.handle.net/10722/284816-
dc.description.abstractOsteosarcoma 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.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturecellbiology-
dc.relation.ispartofNature Cell Biology-
dc.rightsThis is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: https://doi.org/[insert DOI]-
dc.subjectGuanine Nucleotide Dissociation Inhibitors-
dc.subjectGuanosine Triphosphate-
dc.subjectGTPase-Activating Proteins-
dc.titleChromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma-
dc.typeArticle-
dc.identifier.emailDeng, W: wdeng@hku.hk-
dc.identifier.authorityDeng, W=rp01640-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/s41556-020-0522-z-
dc.identifier.pmid32483387-
dc.identifier.scopuseid_2-s2.0-85085881393-
dc.identifier.hkuros312315-
dc.identifier.hkuros314315-
dc.identifier.volume22-
dc.identifier.issue7-
dc.identifier.spage868-
dc.identifier.epage881-
dc.identifier.isiWOS:000537044700001-
dc.publisher.placeUnited Kingdom-
dc.relation.erratumdoi:10.1038/s41556-020-0541-9-
dc.identifier.issnl1465-7392-

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