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Interfering with the interaction between ErbB1, nucleolin and Ras as a potential treatment for glioblastoma
The three oncogenes, ErbB receptors, Ras proteins and nucleolin may contribute to malignant transformation. Previously, we demonstrated that nucleolin could bind both Ras protein and ErbB receptors. We also showed that the crosstalk between the three proteins facilitates anchorage independent growth...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226707/ https://www.ncbi.nlm.nih.gov/pubmed/25261371 |
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author | Goldshmit, Yona Trangle, Sari Schokoroy Kloog, Yoel Pinkas-Kramarski, Ronit |
author_facet | Goldshmit, Yona Trangle, Sari Schokoroy Kloog, Yoel Pinkas-Kramarski, Ronit |
author_sort | Goldshmit, Yona |
collection | PubMed |
description | The three oncogenes, ErbB receptors, Ras proteins and nucleolin may contribute to malignant transformation. Previously, we demonstrated that nucleolin could bind both Ras protein and ErbB receptors. We also showed that the crosstalk between the three proteins facilitates anchorage independent growth and tumor growth in nude mice, and that inhibition of this interaction in prostate and colon cancer cells reduces tumorigenicity. In the present study, we show that treatment with Ras and nucleolin inhibitors reduces the oncogenic effect induced by ErbB1 receptor in U87-MG cells. This combined treatment enhances cell death, reduces cell proliferation and cell migration. Moreover, we demonstrate a pivotal role of nucleolin in ErbB1 activation by its ligand. Nucleolin inhibitor prevents EGF-induced receptor activation and its downstream signaling followed by reduced proliferation. Furthermore, inhibition of Ras by Salirasib (FTS), mainly reduces cell viability and motility. The combined treatment, which targets both Ras and nucleolin, additively reduces tumorigenicity both in vitro and in vivo. These results suggest that targeting both nucleolin and Ras may represent an additional opportunity for inhibiting cancers, including glioblastoma, that are driven by these oncogenes. |
format | Online Article Text |
id | pubmed-4226707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-42267072014-11-17 Interfering with the interaction between ErbB1, nucleolin and Ras as a potential treatment for glioblastoma Goldshmit, Yona Trangle, Sari Schokoroy Kloog, Yoel Pinkas-Kramarski, Ronit Oncotarget Research Paper The three oncogenes, ErbB receptors, Ras proteins and nucleolin may contribute to malignant transformation. Previously, we demonstrated that nucleolin could bind both Ras protein and ErbB receptors. We also showed that the crosstalk between the three proteins facilitates anchorage independent growth and tumor growth in nude mice, and that inhibition of this interaction in prostate and colon cancer cells reduces tumorigenicity. In the present study, we show that treatment with Ras and nucleolin inhibitors reduces the oncogenic effect induced by ErbB1 receptor in U87-MG cells. This combined treatment enhances cell death, reduces cell proliferation and cell migration. Moreover, we demonstrate a pivotal role of nucleolin in ErbB1 activation by its ligand. Nucleolin inhibitor prevents EGF-induced receptor activation and its downstream signaling followed by reduced proliferation. Furthermore, inhibition of Ras by Salirasib (FTS), mainly reduces cell viability and motility. The combined treatment, which targets both Ras and nucleolin, additively reduces tumorigenicity both in vitro and in vivo. These results suggest that targeting both nucleolin and Ras may represent an additional opportunity for inhibiting cancers, including glioblastoma, that are driven by these oncogenes. Impact Journals LLC 2014-08-12 /pmc/articles/PMC4226707/ /pubmed/25261371 Text en Copyright: © 2014 Goldshmit et al. http://creativecommons.org/licenses/by/2.5/ 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 credited. |
spellingShingle | Research Paper Goldshmit, Yona Trangle, Sari Schokoroy Kloog, Yoel Pinkas-Kramarski, Ronit Interfering with the interaction between ErbB1, nucleolin and Ras as a potential treatment for glioblastoma |
title | Interfering with the interaction between ErbB1, nucleolin and Ras as a potential treatment for glioblastoma |
title_full | Interfering with the interaction between ErbB1, nucleolin and Ras as a potential treatment for glioblastoma |
title_fullStr | Interfering with the interaction between ErbB1, nucleolin and Ras as a potential treatment for glioblastoma |
title_full_unstemmed | Interfering with the interaction between ErbB1, nucleolin and Ras as a potential treatment for glioblastoma |
title_short | Interfering with the interaction between ErbB1, nucleolin and Ras as a potential treatment for glioblastoma |
title_sort | interfering with the interaction between erbb1, nucleolin and ras as a potential treatment for glioblastoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226707/ https://www.ncbi.nlm.nih.gov/pubmed/25261371 |
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