Hepatocyte Nuclear Factor 4 Alpha Promotes The Invasion, Metastasis And Angiogenesis Of Neuroblastoma Cells Via Targeting Matrix Metalloproteinase 14

Keywords

Hepatocyte nuclear factor 4 alpha; Matrix metalloproteinase 14; Neuroblastoma; Transcriptional regulation

Abstract

Matrix metalloproteinase 14 (MMP-14) is the only membrane-anchored MMP that plays critical roles in tumorigenesis and aggressiveness. However, the regulatory mechanisms underlying the high MMP-14 expression in neuroblastoma (NB), a highly malignant tumor in childhood, still remain unclear. Herein, we applied an integrative approach to analyze the public datasets, and identified hepatocyte nuclear factor 4 alpha (HNF4α) as a crucial transcription factor facilitating the MMP-14 expression in NB. In clinical NB tissues, HNF4α was up-regulated and positively correlated with MMP-14 expression, and was an independent prognostic factor for unfavorable outcome of patients. Luciferase reporter and chromatin immunoprecipitation assays indicated that HNF4α directly targeted the binding site within the MMP-14 promoter to facilitate its transcription. Knockdown of HNF4α suppressed the invasion, metastasis and angiogenesis of NB cells in vitro and in vivo. Conversely, ectopic expression of HNF4α promoted the invasion, metastasis and angiogenesis of NB cells. Importantly, restoration of MMP-14 expression prevented the tumor cells from HNF4α-mediated changes in these biological features. Taken together, HNF4α exhibits oncogenic activity that affects the aggressiveness and angiogenesis of NB through activating the transcription of MMP-14.

Publication Date

4-10-2015

Publication Title

Cancer Letters

Volume

359

Issue

2

Number of Pages

187-197

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.canlet.2015.01.008

Socpus ID

84923115145 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84923115145

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