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Mucin 1-mediated chemo-resistance in lung cancer cells
Paclitaxel (PTX) is a commonly used drug to treat diverse cancer types. However, its treatment can generate resistance and the mechanisms of PTX-resistance in lung cancers are still unclear. We demonstrated that non-small cell lung cancers (NSCLCs) survive PTX treatment. Compared with the progenitor...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728677/ https://www.ncbi.nlm.nih.gov/pubmed/26779808 http://dx.doi.org/10.1038/oncsis.2015.47 |
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author | Ham, S Y Kwon, T Bak, Y Yu, J-H Hong, J Lee, S K Yu, D-Y Yoon, D-Y |
author_facet | Ham, S Y Kwon, T Bak, Y Yu, J-H Hong, J Lee, S K Yu, D-Y Yoon, D-Y |
author_sort | Ham, S Y |
collection | PubMed |
description | Paclitaxel (PTX) is a commonly used drug to treat diverse cancer types. However, its treatment can generate resistance and the mechanisms of PTX-resistance in lung cancers are still unclear. We demonstrated that non-small cell lung cancers (NSCLCs) survive PTX treatment. Compared with the progenitor NSCLC A549 cells, the PTX-resistant A549 cells (A549/PTX) displayed enhanced sphere-formation ability. The proportion of the cancer stem cell marker, aldehyde dehydrogenase-positive cells, and epithelial–mesenchymal transition signaling protein levels were also elevated in A549/PTX. Importantly, the levels of oncoproteins phosphoinositide-3 kinase/Akt, mucin 1 cytoplasmic domain (MUC1-C) and β-catenin were also significantly elevated in A549/PTX. Furthermore, nuclear translocation of MUC1-C and β-catenin increased in A549/PTX. The c-SRC protein, an activator of MUC1-C, was also overexpressed in A549/PTX. These observations led to the hypothesis that enhanced expression of MUC1-C is associated with stemness and PTX resistance in NSCLCs. To test this, we knocked down or overexpressed MUC1-C in A549/PTX and found that inhibition of MUC1-C expression coupled with PTX treatment was sufficient to reduce the sphere-forming ability and survival of A549/PTX. In summary, our in vitro and in vivo studies have revealed a potential mechanism of MUC1-C-mediated PTX resistance and provided insights into a novel therapeutic measure for lung cancers. |
format | Online Article Text |
id | pubmed-4728677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47286772016-02-08 Mucin 1-mediated chemo-resistance in lung cancer cells Ham, S Y Kwon, T Bak, Y Yu, J-H Hong, J Lee, S K Yu, D-Y Yoon, D-Y Oncogenesis Original Article Paclitaxel (PTX) is a commonly used drug to treat diverse cancer types. However, its treatment can generate resistance and the mechanisms of PTX-resistance in lung cancers are still unclear. We demonstrated that non-small cell lung cancers (NSCLCs) survive PTX treatment. Compared with the progenitor NSCLC A549 cells, the PTX-resistant A549 cells (A549/PTX) displayed enhanced sphere-formation ability. The proportion of the cancer stem cell marker, aldehyde dehydrogenase-positive cells, and epithelial–mesenchymal transition signaling protein levels were also elevated in A549/PTX. Importantly, the levels of oncoproteins phosphoinositide-3 kinase/Akt, mucin 1 cytoplasmic domain (MUC1-C) and β-catenin were also significantly elevated in A549/PTX. Furthermore, nuclear translocation of MUC1-C and β-catenin increased in A549/PTX. The c-SRC protein, an activator of MUC1-C, was also overexpressed in A549/PTX. These observations led to the hypothesis that enhanced expression of MUC1-C is associated with stemness and PTX resistance in NSCLCs. To test this, we knocked down or overexpressed MUC1-C in A549/PTX and found that inhibition of MUC1-C expression coupled with PTX treatment was sufficient to reduce the sphere-forming ability and survival of A549/PTX. In summary, our in vitro and in vivo studies have revealed a potential mechanism of MUC1-C-mediated PTX resistance and provided insights into a novel therapeutic measure for lung cancers. Nature Publishing Group 2016-01 2016-01-18 /pmc/articles/PMC4728677/ /pubmed/26779808 http://dx.doi.org/10.1038/oncsis.2015.47 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Oncogenesis is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Ham, S Y Kwon, T Bak, Y Yu, J-H Hong, J Lee, S K Yu, D-Y Yoon, D-Y Mucin 1-mediated chemo-resistance in lung cancer cells |
title | Mucin 1-mediated chemo-resistance in lung cancer cells |
title_full | Mucin 1-mediated chemo-resistance in lung cancer cells |
title_fullStr | Mucin 1-mediated chemo-resistance in lung cancer cells |
title_full_unstemmed | Mucin 1-mediated chemo-resistance in lung cancer cells |
title_short | Mucin 1-mediated chemo-resistance in lung cancer cells |
title_sort | mucin 1-mediated chemo-resistance in lung cancer cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728677/ https://www.ncbi.nlm.nih.gov/pubmed/26779808 http://dx.doi.org/10.1038/oncsis.2015.47 |
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