MMP7-mediated cleavage of nucleolin at Asp255 induces MMP9 expression to promote tumor malignancy

Tai I. Hsu, S. C. Lin, P. S. Lu, Wen-Chang Chang, C. Y. Hung, Y. M. Yeh, Wu Chou Su, Pao Chi Liao, Jan Jong Hung

研究成果: 雜誌貢獻文章

21 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)826-837
頁數12
期刊Oncogene
34
發行號7
DOIs
出版狀態已發佈 - 二月 12 2015

    指紋

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics
  • Medicine(all)

引用此

Hsu, T. I., Lin, S. C., Lu, P. S., Chang, W-C., Hung, C. Y., Yeh, Y. M., Su, W. C., Liao, P. C., & Hung, J. J. (2015). MMP7-mediated cleavage of nucleolin at Asp255 induces MMP9 expression to promote tumor malignancy. Oncogene, 34(7), 826-837. https://doi.org/10.1038/onc.2014.22