Akt2 Regulates Metastatic Potential in Neuroblastoma

Jingbo Qiao, Sora Lee, Pritha Paul, Lan Qiao, Chase J. Taylor, Cameron Schlegel, Nadja C. Colon, Dai H. Chung

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Activation of PI3K/AKT pathway correlates with poor prognosis in patients with neuroblastoma. Our previous studies have demonstrated that PI3K/AKT signaling is critical for the oncogenic transformations induced by gastrin-releasing peptide (GRP) and its receptor, GRP-R, in neuroblastoma. Moreover, PI3K/AKT-dependent oncogenic transformations require N-myc, an extensively studied oncogene in neuroblastoma. Whether AKT directly regulates the expression of N-myc oncogene is yet to be determined. Here, we report a novel finding that of the three AKT isoforms, AKT2 specifically regulated N-myc expression in neuroblastoma cells. We also confirmed that GRP-R is upstream of AKT2 and in turn, regulated N-myc expression via AKT2 in neuroblastoma cells. Functional assays demonstrated that attenuation of AKT2 impaired cell proliferation and anchorage-independent cell growth, and decreased the secretion of angiogenic factor VEGF in vitro. Furthermore, silencing AKT2 inhibited migration and invasion of neuroblastoma cells in vitro. Xenografts established by injecting AKT2 silenced human neuroblastoma cells into murine spleen expressed decreased levels of AKT2 and resulted in fewer liver metastases compared to controls in vivo. Hence, our study highlights the potential molecular mechanism(s) mediating the oncogenic role of GRP/GRP-R and demonstrates a novel role for AKT2 in neuroblastoma tumorigenesis, indicating that targeting the GRP/GRP-R/AKT2 axis may be important for developing novel therapeutics in the treatment of clinically aggressive neuroblastoma.

Original languageEnglish (US)
Article numbere56382
JournalPloS one
Volume8
Issue number2
DOIs
StatePublished - Feb 26 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Qiao, J., Lee, S., Paul, P., Qiao, L., Taylor, C. J., Schlegel, C., Colon, N. C., & Chung, D. H. (2013). Akt2 Regulates Metastatic Potential in Neuroblastoma. PloS one, 8(2), [e56382]. https://doi.org/10.1371/journal.pone.0056382