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NSCLC depend upon YAP expression and nuclear localization after acquiring resistance to EGFR inhibitors
Yes-associated protein (YAP) is a downstream target of the Hippo pathway and has been found to be oncogenic driving many cancers into developing metastatic phenotypes leading to poor survival outcomes. This study investigated if YAP expression is associated with drug resistance in two non-small cell...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489647/ https://www.ncbi.nlm.nih.gov/pubmed/28680534 http://dx.doi.org/10.18632/genesandcancer.136 |
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author | McGowan, Marc Kleinberg, Lilach Halvorsen, Ann Rita Helland, Åslaug Brustugun, Odd Terje |
author_facet | McGowan, Marc Kleinberg, Lilach Halvorsen, Ann Rita Helland, Åslaug Brustugun, Odd Terje |
author_sort | McGowan, Marc |
collection | PubMed |
description | Yes-associated protein (YAP) is a downstream target of the Hippo pathway and has been found to be oncogenic driving many cancers into developing metastatic phenotypes leading to poor survival outcomes. This study investigated if YAP expression is associated with drug resistance in two non-small cell lung cancer (NSCLC) lines (HCC827 and H1975) generated to become resistant to the EGFR tyrosine kinase inhibitors (EGFR TKI) erlotinib, gefitinib or the T790M-specific osimertinib. We found that acquired EGFR TKI resistance was associated with YAP over-expression (osimertinib-resistant cells) or YAP amplification (erlotinib- and gefitinib-resistant cells) along with EMT phenotypic changes. YAP was localized in the nucleus, indicative of active protein. siRNA-mediated silencing of YAP resulted in re-sensitizing the drug-resistant cells to EGFR TKI compared to the negative siRNA controls (p = <0.05). These results suggest YAP is a potential mechanism of EGFR-TKI resistance in NSCLC and may presents itself as a viable therapeutic target. |
format | Online Article Text |
id | pubmed-5489647 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-54896472017-07-05 NSCLC depend upon YAP expression and nuclear localization after acquiring resistance to EGFR inhibitors McGowan, Marc Kleinberg, Lilach Halvorsen, Ann Rita Helland, Åslaug Brustugun, Odd Terje Genes Cancer Research Paper Yes-associated protein (YAP) is a downstream target of the Hippo pathway and has been found to be oncogenic driving many cancers into developing metastatic phenotypes leading to poor survival outcomes. This study investigated if YAP expression is associated with drug resistance in two non-small cell lung cancer (NSCLC) lines (HCC827 and H1975) generated to become resistant to the EGFR tyrosine kinase inhibitors (EGFR TKI) erlotinib, gefitinib or the T790M-specific osimertinib. We found that acquired EGFR TKI resistance was associated with YAP over-expression (osimertinib-resistant cells) or YAP amplification (erlotinib- and gefitinib-resistant cells) along with EMT phenotypic changes. YAP was localized in the nucleus, indicative of active protein. siRNA-mediated silencing of YAP resulted in re-sensitizing the drug-resistant cells to EGFR TKI compared to the negative siRNA controls (p = <0.05). These results suggest YAP is a potential mechanism of EGFR-TKI resistance in NSCLC and may presents itself as a viable therapeutic target. Impact Journals LLC 2017-03 /pmc/articles/PMC5489647/ /pubmed/28680534 http://dx.doi.org/10.18632/genesandcancer.136 Text en Copyright: © 2017 McGowan et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper McGowan, Marc Kleinberg, Lilach Halvorsen, Ann Rita Helland, Åslaug Brustugun, Odd Terje NSCLC depend upon YAP expression and nuclear localization after acquiring resistance to EGFR inhibitors |
title | NSCLC depend upon YAP expression and nuclear localization after acquiring resistance to EGFR inhibitors |
title_full | NSCLC depend upon YAP expression and nuclear localization after acquiring resistance to EGFR inhibitors |
title_fullStr | NSCLC depend upon YAP expression and nuclear localization after acquiring resistance to EGFR inhibitors |
title_full_unstemmed | NSCLC depend upon YAP expression and nuclear localization after acquiring resistance to EGFR inhibitors |
title_short | NSCLC depend upon YAP expression and nuclear localization after acquiring resistance to EGFR inhibitors |
title_sort | nsclc depend upon yap expression and nuclear localization after acquiring resistance to egfr inhibitors |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489647/ https://www.ncbi.nlm.nih.gov/pubmed/28680534 http://dx.doi.org/10.18632/genesandcancer.136 |
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