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Fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the PI3K/Akt pathway
BACKGROUND: A major therapeutic challenge for breast cancer is the ability of cancer cells to evade killing of conventional chemotherapeutic agents. We have recently reported the actin-bundling protein (fascin) as a major regulator of breast cancer metastasis and survival. METHODS: Survival of breas...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200093/ https://www.ncbi.nlm.nih.gov/pubmed/25117814 http://dx.doi.org/10.1038/bjc.2014.453 |
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author | Ghebeh, H Al-Khaldi, S Olabi, S Al-Dhfyan, A Al-Mohanna, F Barnawi, R Tulbah, A Al-Tweigeri, T Ajarim, D Al-Alwan, M |
author_facet | Ghebeh, H Al-Khaldi, S Olabi, S Al-Dhfyan, A Al-Mohanna, F Barnawi, R Tulbah, A Al-Tweigeri, T Ajarim, D Al-Alwan, M |
author_sort | Ghebeh, H |
collection | PubMed |
description | BACKGROUND: A major therapeutic challenge for breast cancer is the ability of cancer cells to evade killing of conventional chemotherapeutic agents. We have recently reported the actin-bundling protein (fascin) as a major regulator of breast cancer metastasis and survival. METHODS: Survival of breast cancer patients that received chemotherapy and xenograft tumour model was used to assess the effect of chemotherapy on fascin-positive and -negative breast cancer cells. Molecular and cellular assays were used to gain in-depth understanding of the relationship between fascin and chemoresistance. RESULTS: We showed a significant correlation between fascin expression and shorter survival in breast cancer patients who received chemotherapy. In xenograft experiments, fascin-positive cancer cells displayed significantly more resistance to chemotherapy-mediated apoptotic cell death than fascin-negative counterparts. This increased chemoresistance was at least partially mediated through PI3K/Akt signalling, and was paralleled by increased FAK phosphorylation, enhanced expression of the inhibitor of apoptosis proteins (XIAP and Livin) and suppression of the proapoptotic markers (caspase 9, caspase 3 and PARP). CONCLUSIONS: This is the first report to demonstrate fascin involvement in breast cancer chemotherapeutic resistance, supporting the development of fascin-targeting drugs for better treatment of chemoresistance breast cancer. |
format | Online Article Text |
id | pubmed-4200093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-42000932014-10-21 Fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the PI3K/Akt pathway Ghebeh, H Al-Khaldi, S Olabi, S Al-Dhfyan, A Al-Mohanna, F Barnawi, R Tulbah, A Al-Tweigeri, T Ajarim, D Al-Alwan, M Br J Cancer Translational Therapeutics BACKGROUND: A major therapeutic challenge for breast cancer is the ability of cancer cells to evade killing of conventional chemotherapeutic agents. We have recently reported the actin-bundling protein (fascin) as a major regulator of breast cancer metastasis and survival. METHODS: Survival of breast cancer patients that received chemotherapy and xenograft tumour model was used to assess the effect of chemotherapy on fascin-positive and -negative breast cancer cells. Molecular and cellular assays were used to gain in-depth understanding of the relationship between fascin and chemoresistance. RESULTS: We showed a significant correlation between fascin expression and shorter survival in breast cancer patients who received chemotherapy. In xenograft experiments, fascin-positive cancer cells displayed significantly more resistance to chemotherapy-mediated apoptotic cell death than fascin-negative counterparts. This increased chemoresistance was at least partially mediated through PI3K/Akt signalling, and was paralleled by increased FAK phosphorylation, enhanced expression of the inhibitor of apoptosis proteins (XIAP and Livin) and suppression of the proapoptotic markers (caspase 9, caspase 3 and PARP). CONCLUSIONS: This is the first report to demonstrate fascin involvement in breast cancer chemotherapeutic resistance, supporting the development of fascin-targeting drugs for better treatment of chemoresistance breast cancer. Nature Publishing Group 2014-10-14 2014-08-12 /pmc/articles/PMC4200093/ /pubmed/25117814 http://dx.doi.org/10.1038/bjc.2014.453 Text en Copyright © 2014 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Translational Therapeutics Ghebeh, H Al-Khaldi, S Olabi, S Al-Dhfyan, A Al-Mohanna, F Barnawi, R Tulbah, A Al-Tweigeri, T Ajarim, D Al-Alwan, M Fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the PI3K/Akt pathway |
title | Fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the PI3K/Akt pathway |
title_full | Fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the PI3K/Akt pathway |
title_fullStr | Fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the PI3K/Akt pathway |
title_full_unstemmed | Fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the PI3K/Akt pathway |
title_short | Fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the PI3K/Akt pathway |
title_sort | fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the pi3k/akt pathway |
topic | Translational Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200093/ https://www.ncbi.nlm.nih.gov/pubmed/25117814 http://dx.doi.org/10.1038/bjc.2014.453 |
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