EWS-FLI1-mediated tenascin-C expression promotes tumour progression by targeting MALAT1 through integrin α5ß1-mediated YAP activation in Ewing sarcoma.
Br J Cancer
; 121(11): 922-933, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31649319
ABSTRACT
BACKGROUND:
The extracellular matrix has been critically associated with the tumorigenesis and progression of Ewing sarcoma (ES). However, the regulatory and prognostic roles of tenascin-C (TNC) in ES remain unclear.METHODS:
TNC expression was examined in specimens by immunohistochemistry, and the association of TNC expression with ES patient survival was also analysed. TNC-knockout cell lines were constructed using CRISPR/Cas9 methods. In vitro experiments and in vivo bioluminescent imaging using BALB/c nude mice were conducted to evaluate the effect of TNC on ES tumour progression. RNA sequencing was performed, and the underlying mechanism of TNC was further explored.RESULTS:
TNC was overexpressed in ES tissue and cell lines, and TNC overexpression was associated with poor survival in ES patients. TNC enhanced cell proliferation, migration and angiogenesis in vitro and promoted ES metastasis in vivo. The oncoprotein EWS-FLI1 profoundly increased TNC expression by directly binding to the TNC promoter region. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) upregulation induced by Yes-associated protein (YAP) activation was responsible for TNC-regulated ES tumour progression. Activated integrin α5ß1 signalling might be correlated with YAP dephosphorylation and nuclear translocation.CONCLUSIONS:
TNC may promote ES tumour progression by targeting MALAT1 through integrin α5ß1-mediated YAP activation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sarcoma de Ewing
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Fatores de Transcrição
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Proteínas de Fusão Oncogênica
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Proteínas de Ciclo Celular
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Tenascina
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Proteína EWS de Ligação a RNA
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Integrina alfa5beta1
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Proteína Proto-Oncogênica c-fli-1
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RNA Longo não Codificante
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Carcinogênese
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Animals
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Child
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Child, preschool
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2019
Tipo de documento:
Article