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Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways
Breast cancer is the most prevalent cancer in women worldwide. About 15–20% of all breast cancers are triple negative breast cancer (TNBC) and are often highly aggressive when compared to other subtypes of breast cancers. To better characterize the biology that underlies the TNBC phenotype, we profi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745717/ https://www.ncbi.nlm.nih.gov/pubmed/26356563 |
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author | Wu, Xinyan Zahari, Muhammad Saddiq Ma, Binyun Liu, Ren Renuse, Santosh Sahasrabuddhe, Nandini A. Chen, Lily Chaerkady, Raghothama Kim, Min-Sik Zhong, Jun Jelinek, Christine Barbhuiya, Mustafa A. Leal-Rojas, Pamela Yang, Yi Kashyap, Manoj Kumar Marimuthu, Arivusudar Ling, Min Fackler, Mary Jo Merino, Vanessa Zhang, Zhen Zahnow, Cynthia A. Gabrielson, Edward Stearns, Vered Roa, Juan Carlos Sukumar, Saraswati Gill, Parkash S. Pandey, Akhilesh |
author_facet | Wu, Xinyan Zahari, Muhammad Saddiq Ma, Binyun Liu, Ren Renuse, Santosh Sahasrabuddhe, Nandini A. Chen, Lily Chaerkady, Raghothama Kim, Min-Sik Zhong, Jun Jelinek, Christine Barbhuiya, Mustafa A. Leal-Rojas, Pamela Yang, Yi Kashyap, Manoj Kumar Marimuthu, Arivusudar Ling, Min Fackler, Mary Jo Merino, Vanessa Zhang, Zhen Zahnow, Cynthia A. Gabrielson, Edward Stearns, Vered Roa, Juan Carlos Sukumar, Saraswati Gill, Parkash S. Pandey, Akhilesh |
author_sort | Wu, Xinyan |
collection | PubMed |
description | Breast cancer is the most prevalent cancer in women worldwide. About 15–20% of all breast cancers are triple negative breast cancer (TNBC) and are often highly aggressive when compared to other subtypes of breast cancers. To better characterize the biology that underlies the TNBC phenotype, we profiled the phosphotyrosine proteome of a panel of twenty-six TNBC cell lines using quantitative high resolution Fourier transform mass spectrometry. A heterogeneous pattern of tyrosine kinase activation was observed based on 1,789 tyrosine-phosphorylated peptides identified from 969 proteins. One of the tyrosine kinases, AXL, was found to be activated in a majority of aggressive TNBC cell lines and was accompanied by a higher level of AXL expression. High levels of AXL expression are correlated with a significant decrease in patient survival. Treatment of cells bearing activated AXL with a humanized AXL antibody inhibited cell proliferation and migration in vitro, and tumor growth in mice. Overall, our global phosphoproteomic analysis provided new insights into the heterogeneity in the activation status of tyrosine kinase pathways in TNBCs. Our approach presents an effective means of identifying important novel biomarkers and targets for therapy such as AXL in TNBC. |
format | Online Article Text |
id | pubmed-4745717 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-47457172016-02-23 Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways Wu, Xinyan Zahari, Muhammad Saddiq Ma, Binyun Liu, Ren Renuse, Santosh Sahasrabuddhe, Nandini A. Chen, Lily Chaerkady, Raghothama Kim, Min-Sik Zhong, Jun Jelinek, Christine Barbhuiya, Mustafa A. Leal-Rojas, Pamela Yang, Yi Kashyap, Manoj Kumar Marimuthu, Arivusudar Ling, Min Fackler, Mary Jo Merino, Vanessa Zhang, Zhen Zahnow, Cynthia A. Gabrielson, Edward Stearns, Vered Roa, Juan Carlos Sukumar, Saraswati Gill, Parkash S. Pandey, Akhilesh Oncotarget Research Paper Breast cancer is the most prevalent cancer in women worldwide. About 15–20% of all breast cancers are triple negative breast cancer (TNBC) and are often highly aggressive when compared to other subtypes of breast cancers. To better characterize the biology that underlies the TNBC phenotype, we profiled the phosphotyrosine proteome of a panel of twenty-six TNBC cell lines using quantitative high resolution Fourier transform mass spectrometry. A heterogeneous pattern of tyrosine kinase activation was observed based on 1,789 tyrosine-phosphorylated peptides identified from 969 proteins. One of the tyrosine kinases, AXL, was found to be activated in a majority of aggressive TNBC cell lines and was accompanied by a higher level of AXL expression. High levels of AXL expression are correlated with a significant decrease in patient survival. Treatment of cells bearing activated AXL with a humanized AXL antibody inhibited cell proliferation and migration in vitro, and tumor growth in mice. Overall, our global phosphoproteomic analysis provided new insights into the heterogeneity in the activation status of tyrosine kinase pathways in TNBCs. Our approach presents an effective means of identifying important novel biomarkers and targets for therapy such as AXL in TNBC. Impact Journals LLC 2015-09-03 /pmc/articles/PMC4745717/ /pubmed/26356563 Text en Copyright: © 2015 Wu 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 Wu, Xinyan Zahari, Muhammad Saddiq Ma, Binyun Liu, Ren Renuse, Santosh Sahasrabuddhe, Nandini A. Chen, Lily Chaerkady, Raghothama Kim, Min-Sik Zhong, Jun Jelinek, Christine Barbhuiya, Mustafa A. Leal-Rojas, Pamela Yang, Yi Kashyap, Manoj Kumar Marimuthu, Arivusudar Ling, Min Fackler, Mary Jo Merino, Vanessa Zhang, Zhen Zahnow, Cynthia A. Gabrielson, Edward Stearns, Vered Roa, Juan Carlos Sukumar, Saraswati Gill, Parkash S. Pandey, Akhilesh Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways |
title | Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways |
title_full | Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways |
title_fullStr | Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways |
title_full_unstemmed | Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways |
title_short | Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways |
title_sort | global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745717/ https://www.ncbi.nlm.nih.gov/pubmed/26356563 |
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