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Disrupting the Oncogenic Synergism between Nucleolin and Ras Results in Cell Growth Inhibition and Cell Death
BACKGROUND: The ErbB receptors, Ras proteins and nucleolin are major contributors to malignant transformation. The pleiotropic protein nucleolin can bind to both Ras protein and ErbB receptors. Previously, we have demonstrated a crosstalk between Ras, nucleolin and the ErbB1 receptor. Activated Ras...
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/PMC3782480/ https://www.ncbi.nlm.nih.gov/pubmed/24086490 http://dx.doi.org/10.1371/journal.pone.0075269 |
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author | Schokoroy, Sari Juster, Dolly Kloog, Yoel Pinkas-Kramarski, Ronit |
author_facet | Schokoroy, Sari Juster, Dolly Kloog, Yoel Pinkas-Kramarski, Ronit |
author_sort | Schokoroy, Sari |
collection | PubMed |
description | BACKGROUND: The ErbB receptors, Ras proteins and nucleolin are major contributors to malignant transformation. The pleiotropic protein nucleolin can bind to both Ras protein and ErbB receptors. Previously, we have demonstrated a crosstalk between Ras, nucleolin and the ErbB1 receptor. Activated Ras facilitates nucleolin interaction with ErbB1 and stabilizes ErbB1 levels. The three oncogenes synergistically facilitate anchorage independent growth and tumor growth in nude mice. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we used several cancer cell lines. The effect of Ras and nucleolin inhibition was determined using cell growth, cell death and cell motility assays. Protein expression was determined by immunohistochemistry. We found that inhibition of Ras and nucleolin reduces tumor cell growth, enhances cell death and inhibits anchorage independent growth. Our results reveal that the combined treatment affects Ras and nucleolin levels and localization. Our study also indicates that Salirasib (FTS, Ras inhibitor) reduces cell motility, which is not affected by the nucleolin inhibitor. CONCLUSIONS/SIGNIFICANCE: These results suggest that targeting both nucleolin and Ras may represent an additional avenue for inhibiting cancers driven by these oncogenes. |
format | Online Article Text |
id | pubmed-3782480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37824802013-10-01 Disrupting the Oncogenic Synergism between Nucleolin and Ras Results in Cell Growth Inhibition and Cell Death Schokoroy, Sari Juster, Dolly Kloog, Yoel Pinkas-Kramarski, Ronit PLoS One Research Article BACKGROUND: The ErbB receptors, Ras proteins and nucleolin are major contributors to malignant transformation. The pleiotropic protein nucleolin can bind to both Ras protein and ErbB receptors. Previously, we have demonstrated a crosstalk between Ras, nucleolin and the ErbB1 receptor. Activated Ras facilitates nucleolin interaction with ErbB1 and stabilizes ErbB1 levels. The three oncogenes synergistically facilitate anchorage independent growth and tumor growth in nude mice. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we used several cancer cell lines. The effect of Ras and nucleolin inhibition was determined using cell growth, cell death and cell motility assays. Protein expression was determined by immunohistochemistry. We found that inhibition of Ras and nucleolin reduces tumor cell growth, enhances cell death and inhibits anchorage independent growth. Our results reveal that the combined treatment affects Ras and nucleolin levels and localization. Our study also indicates that Salirasib (FTS, Ras inhibitor) reduces cell motility, which is not affected by the nucleolin inhibitor. CONCLUSIONS/SIGNIFICANCE: These results suggest that targeting both nucleolin and Ras may represent an additional avenue for inhibiting cancers driven by these oncogenes. Public Library of Science 2013-09-24 /pmc/articles/PMC3782480/ /pubmed/24086490 http://dx.doi.org/10.1371/journal.pone.0075269 Text en © 2013 Schokoroy 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 Schokoroy, Sari Juster, Dolly Kloog, Yoel Pinkas-Kramarski, Ronit Disrupting the Oncogenic Synergism between Nucleolin and Ras Results in Cell Growth Inhibition and Cell Death |
title | Disrupting the Oncogenic Synergism between Nucleolin and Ras Results in Cell Growth Inhibition and Cell Death |
title_full | Disrupting the Oncogenic Synergism between Nucleolin and Ras Results in Cell Growth Inhibition and Cell Death |
title_fullStr | Disrupting the Oncogenic Synergism between Nucleolin and Ras Results in Cell Growth Inhibition and Cell Death |
title_full_unstemmed | Disrupting the Oncogenic Synergism between Nucleolin and Ras Results in Cell Growth Inhibition and Cell Death |
title_short | Disrupting the Oncogenic Synergism between Nucleolin and Ras Results in Cell Growth Inhibition and Cell Death |
title_sort | disrupting the oncogenic synergism between nucleolin and ras results in cell growth inhibition and cell death |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782480/ https://www.ncbi.nlm.nih.gov/pubmed/24086490 http://dx.doi.org/10.1371/journal.pone.0075269 |
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