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Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation
Small cell lung cancer (SCLC) is the most aggressive type of lung cancer with high mortality. One of the MYC family genes, MYC, MYCL or MYCN, is amplified in ~20% of the SCLCs; therefore, MYC proteins are potential therapeutic targets in SCLC patients. We investigated the therapeutic impact of Omomy...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058735/ https://www.ncbi.nlm.nih.gov/pubmed/27105536 http://dx.doi.org/10.18632/oncotarget.8826 |
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author | Fiorentino, Francesco Paolo Tokgün, Elvan Solé-Sánchez, Sònia Giampaolo, Sabrina Tokgün, Onur Jauset, Toni Kohno, Takashi Perucho, Manuel Soucek, Laura Yokota, Jun |
author_facet | Fiorentino, Francesco Paolo Tokgün, Elvan Solé-Sánchez, Sònia Giampaolo, Sabrina Tokgün, Onur Jauset, Toni Kohno, Takashi Perucho, Manuel Soucek, Laura Yokota, Jun |
author_sort | Fiorentino, Francesco Paolo |
collection | PubMed |
description | Small cell lung cancer (SCLC) is the most aggressive type of lung cancer with high mortality. One of the MYC family genes, MYC, MYCL or MYCN, is amplified in ~20% of the SCLCs; therefore, MYC proteins are potential therapeutic targets in SCLC patients. We investigated the therapeutic impact of Omomyc, a MYC dominant negative, in a panel of SCLC cell lines. Strikingly, Omomyc suppressed the growth of all tested cell lines by inducing cell cycle arrest and/or apoptosis. Induction of G1 arrest by Omomyc was found to be dependent on the activation of CDKN1A, in part, through the TP73 pathway. Our results strongly indicate that SCLC cells carrying amplification of MYC, MYCL or MYCN are addicted to MYC function, suggesting that MYC targeting would be an efficient therapeutic option for SCLC patients. |
format | Online Article Text |
id | pubmed-5058735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50587352016-10-15 Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation Fiorentino, Francesco Paolo Tokgün, Elvan Solé-Sánchez, Sònia Giampaolo, Sabrina Tokgün, Onur Jauset, Toni Kohno, Takashi Perucho, Manuel Soucek, Laura Yokota, Jun Oncotarget Research Paper Small cell lung cancer (SCLC) is the most aggressive type of lung cancer with high mortality. One of the MYC family genes, MYC, MYCL or MYCN, is amplified in ~20% of the SCLCs; therefore, MYC proteins are potential therapeutic targets in SCLC patients. We investigated the therapeutic impact of Omomyc, a MYC dominant negative, in a panel of SCLC cell lines. Strikingly, Omomyc suppressed the growth of all tested cell lines by inducing cell cycle arrest and/or apoptosis. Induction of G1 arrest by Omomyc was found to be dependent on the activation of CDKN1A, in part, through the TP73 pathway. Our results strongly indicate that SCLC cells carrying amplification of MYC, MYCL or MYCN are addicted to MYC function, suggesting that MYC targeting would be an efficient therapeutic option for SCLC patients. Impact Journals LLC 2016-04-18 /pmc/articles/PMC5058735/ /pubmed/27105536 http://dx.doi.org/10.18632/oncotarget.8826 Text en Copyright: © 2016 Fiorentino 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 Fiorentino, Francesco Paolo Tokgün, Elvan Solé-Sánchez, Sònia Giampaolo, Sabrina Tokgün, Onur Jauset, Toni Kohno, Takashi Perucho, Manuel Soucek, Laura Yokota, Jun Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation |
title | Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation |
title_full | Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation |
title_fullStr | Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation |
title_full_unstemmed | Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation |
title_short | Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation |
title_sort | growth suppression by myc inhibition in small cell lung cancer cells with tp53 and rb1 inactivation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058735/ https://www.ncbi.nlm.nih.gov/pubmed/27105536 http://dx.doi.org/10.18632/oncotarget.8826 |
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