MMP7-mediated cleavage of nucleolin at Asp255 induces MMP9 expression to promote tumor malignancy.
Oncogene
; 34(7): 826-37, 2015 Feb 12.
Article
en En
| MEDLINE
| ID: mdl-24632608
ABSTRACT
Nucleolin (NCL) participates in DNA transcription, ribosomal biogenesis and the regulation of RNA stability. However, the contribution of NCL to tumor development is still not clear. Herein, we found that NCL expression correlated with poor prognosis in lung cancer patients. Overexpressed NCL was predominantly cleaved to C-terminal truncated NCL (TNCL). In lung cancer formation, activation of the epidermal growth factor receptor pathway induced NCL expression, and also the expression of matrix metalloproteinase (MMP) 7, which then cleaved NCL at Asp255 to generate TNCL of 55 kDa. TNCL increased the expression of several oncogenes, including MMP9, anaplastic lymphoma kinase (ALK), HIF1a and CBLB, and decreased the expression of tumor suppressors including BRD4, PCM1, TFG and KLF6 by modulating mRNA stability through binding to the 3'-untranslated regions of their transcripts, thus ultimately enhancing metastasis activity. In conclusion, this study identified a novel role of the cleavage form of NCL generated by MMP7 in stabilizing MMP9 mRNA. We also provide a new insight that MMP7 not only cleaves the extracellular matrix to promote tumor invasion but also cleaves NCL, which augment oncogenesis. Blocking NCL cleavage may provide a useful new strategy for lung cancer therapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Regulación Enzimológica de la Expresión Génica
/
Regulación Neoplásica de la Expresión Génica
/
Proteínas de Unión al ARN
/
Metaloproteinasa 9 de la Matriz
/
Metaloproteinasa 7 de la Matriz
/
Proteolisis
/
Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2015
Tipo del documento:
Article
País de afiliación:
Taiwán