FGFR4 promotes nuclear localization of GABP to inhibit cell apoptosis in uterine leiomyosarcoma.
Cell Tissue Res
; 383(2): 865-879, 2021 Feb.
Article
em En
| MEDLINE
| ID: mdl-33151453
ABSTRACT
Fibroblast growth factor receptor 4 (FGFR4) has been indicated as a potential "oncogene" in various types of cancer. However, the effects and underlying mechanisms of FGFR4 on uterine leiomyosarcoma (ULMS) progression remain unclear. In this study, we firstly discovered that FGFR4 was upregulated in ULMS specimens and cell lines and closely associated with poor prognosis of ULMS patients. Cell viability and apoptosis assays showed that FGFR4 deletion inhibited cell proliferation and promoted cell apoptosis. Moreover, FGFR4 silence increased cytoplasmic GABP (GA binding protein) expression, while it decreased the nuclear GABP level to inhibit nuclear localization of GABP. Mechanistically, the inhibition ability of FGFR4 silence on nuclear localization of GABP was mediated via mammalian Ste20-like kinases 1 (MST1) activation, which could promote phosphorylation of large tumor suppressor 1 (LATS1) to reduce nuclear localization of GABP. Gain- and loss-of-functional assays indicated that FGFR4 promoted nuclear localization of GABP to inhibit cell apoptosis in ULMS. In conclusion, our findings indicated that FGFR4 inhibited cell apoptosis in ULMS via the promotion of MST1/LATS1-mediated GABP nuclear localization, shedding light on the underlying mechanism of FGFR4-induced ULMS progression.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Uterinas
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Núcleo Celular
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Apoptose
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Receptor Tipo 4 de Fator de Crescimento de Fibroblastos
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Fator de Transcrição de Proteínas de Ligação GA
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Leiomiossarcoma
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Cell Tissue Res
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China