Disrupting the oncogenic synergism between nucleolin and Ras results in cell growth inhibition and cell death.

<h4>Background</h4>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 recep...

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Autores principales:	Sari Schokoroy, Dolly Juster, Yoel Kloog, Ronit Pinkas-Kramarski
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ac663bc6081f4e80aea6b86f46b086a1
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spelling	oai:doaj.org-article:ac663bc6081f4e80aea6b86f46b086a12021-11-18T08:53:56ZDisrupting the oncogenic synergism between nucleolin and Ras results in cell growth inhibition and cell death.1932-620310.1371/journal.pone.0075269https://doaj.org/article/ac663bc6081f4e80aea6b86f46b086a12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086490/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>These results suggest that targeting both nucleolin and Ras may represent an additional avenue for inhibiting cancers driven by these oncogenes.Sari SchokoroyDolly JusterYoel KloogRonit Pinkas-KramarskiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e75269 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sari Schokoroy Dolly Juster Yoel Kloog Ronit Pinkas-Kramarski Disrupting the oncogenic synergism between nucleolin and Ras results in cell growth inhibition and cell death.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>These results suggest that targeting both nucleolin and Ras may represent an additional avenue for inhibiting cancers driven by these oncogenes.
format	article
author	Sari Schokoroy Dolly Juster Yoel Kloog Ronit Pinkas-Kramarski
author_facet	Sari Schokoroy Dolly Juster Yoel Kloog Ronit Pinkas-Kramarski
author_sort	Sari Schokoroy
title	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_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_sort	disrupting the oncogenic synergism between nucleolin and ras results in cell growth inhibition and cell death.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/ac663bc6081f4e80aea6b86f46b086a1
work_keys_str_mv	AT sarischokoroy disruptingtheoncogenicsynergismbetweennucleolinandrasresultsincellgrowthinhibitionandcelldeath AT dollyjuster disruptingtheoncogenicsynergismbetweennucleolinandrasresultsincellgrowthinhibitionandcelldeath AT yoelkloog disruptingtheoncogenicsynergismbetweennucleolinandrasresultsincellgrowthinhibitionandcelldeath AT ronitpinkaskramarski disruptingtheoncogenicsynergismbetweennucleolinandrasresultsincellgrowthinhibitionandcelldeath
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Disrupting the oncogenic synergism between nucleolin and Ras results in cell growth inhibition and cell death.

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