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Akt2 Regulates Metastatic Potential in Neuroblastoma
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, P...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582607/ https://www.ncbi.nlm.nih.gov/pubmed/23468863 http://dx.doi.org/10.1371/journal.pone.0056382 |
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author | Qiao, Jingbo Lee, Sora Paul, Pritha Qiao, Lan Taylor, Chase J. Schlegel, Cameron Colon, Nadja C. Chung, Dai H. |
author_facet | Qiao, Jingbo Lee, Sora Paul, Pritha Qiao, Lan Taylor, Chase J. Schlegel, Cameron Colon, Nadja C. Chung, Dai H. |
author_sort | Qiao, Jingbo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3582607 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35826072013-03-06 Akt2 Regulates Metastatic Potential in Neuroblastoma Qiao, Jingbo Lee, Sora Paul, Pritha Qiao, Lan Taylor, Chase J. Schlegel, Cameron Colon, Nadja C. Chung, Dai H. PLoS One Research Article 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. Public Library of Science 2013-02-26 /pmc/articles/PMC3582607/ /pubmed/23468863 http://dx.doi.org/10.1371/journal.pone.0056382 Text en © 2013 Qiao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Qiao, Jingbo Lee, Sora Paul, Pritha Qiao, Lan Taylor, Chase J. Schlegel, Cameron Colon, Nadja C. Chung, Dai H. Akt2 Regulates Metastatic Potential in Neuroblastoma |
title | Akt2 Regulates Metastatic Potential in Neuroblastoma |
title_full | Akt2 Regulates Metastatic Potential in Neuroblastoma |
title_fullStr | Akt2 Regulates Metastatic Potential in Neuroblastoma |
title_full_unstemmed | Akt2 Regulates Metastatic Potential in Neuroblastoma |
title_short | Akt2 Regulates Metastatic Potential in Neuroblastoma |
title_sort | akt2 regulates metastatic potential in neuroblastoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582607/ https://www.ncbi.nlm.nih.gov/pubmed/23468863 http://dx.doi.org/10.1371/journal.pone.0056382 |
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