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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...

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Autores principales: Schokoroy, Sari, Juster, Dolly, Kloog, Yoel, Pinkas-Kramarski, Ronit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
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.
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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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