Targeting Aurora kinase-A downregulates cell proliferation and angiogenesis in neuroblastoma

Carmelle Romain, Pritha Paul, Kwang Woon Kim, Sora Lee, Jingbo Qiao, Dai H. Chung

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Purpose Aurora kinase A (AURKA) overexpression is associated with poor prognosis in neuroblastoma and has been described to upregulate VEGF in gastric cancer cells. However, the exact role of AURKA in the regulation of neuroblastoma tumorigenesis remains unknown. We hypothesize that AURKA-mediated stabilization of N-Myc may affect VEGF expression and angiogenesis in neuroblastoma. Therefore, we sought to determine whether inhibition of AURKA modulates neuroblastoma angiogenesis. Methods Cell viability and anchorage-independent growth were determined after silencing AURKA or after treatment with MLN8237, AURKA inhibitor. Immunofluorescence was used to determine N-Myc localization. Human umbilical vein endothelial cells (HUVECs) were used to assess angiogenesis in vitro. Real time-PCR and ELISA were performed to determine VEGF transcription and secretion, respectively. Results Knockdown of AURKA significantly reduced cell proliferation and inhibited anchorage-independent growth. It also decreased N-Myc protein levels and nuclear localization. AURKA inhibition also decreased HUVECs tubule formation along with VEGF transcription and secretion. Similarly, MLN8237 treatment decreased neuroblastoma tumorigenicity in vitro. Conclusions Our findings demonstrate that AURKA plays a critical role in neuroblastoma angiogenesis. AURKA regulates nuclear translocation of N-Myc in neuroblastoma cells, thus potentially affecting cell proliferation, anchorage-independent cell growth, and angiogenesis. Targeting AURKA might provide a novel therapeutic strategy in treating aggressive neuroblastomas.

Original languageEnglish (US)
Pages (from-to)159-165
Number of pages7
JournalJournal of Pediatric Surgery
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Keywords

  • AURKA
  • Angiogenesis
  • N-Myc
  • Neuroblastoma

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

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