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TAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis
Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (T...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959931/ https://www.ncbi.nlm.nih.gov/pubmed/29777109 http://dx.doi.org/10.1038/s41467-018-04460-w |
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author | Iriondo, Oihana Liu, Yarong Lee, Grace Elhodaky, Mostafa Jimenez, Christian Li, Lin Lang, Julie Wang, Pin Yu, Min |
author_facet | Iriondo, Oihana Liu, Yarong Lee, Grace Elhodaky, Mostafa Jimenez, Christian Li, Lin Lang, Julie Wang, Pin Yu, Min |
author_sort | Iriondo, Oihana |
collection | PubMed |
description | Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (TAK1) inhibitor 5Z-7-Oxozeaenol can inhibit TNBC lung metastasis in most animals tested. P38 is a central signal downstream of TAK1 in TNBC cells in TAK1-mediated response to multiple cytokines. Following co-culturing with macrophages or fibroblasts, TNBC cells express interleukin-1 (IL1) or tumor necrosis factor-α (TNFα), respectively. Compared to TAK1 inhibition, suppressing IL1 signaling with recombinant IL1 receptor antagonist (IL1RA) is less efficient in reducing lung metastasis, possibly due to the additional TAK1 signals coming from distinct stromal cells. Together, these observations suggest that TAK1 may play a central role in promoting TNBC cell adaptation to the lung microenvironment by facilitating positive feedback signaling mediated by P38. Approaches targeting the key TAK1-P38 signal could offer a novel means for suppressing TNBC lung metastasis. |
format | Online Article Text |
id | pubmed-5959931 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59599312018-05-21 TAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis Iriondo, Oihana Liu, Yarong Lee, Grace Elhodaky, Mostafa Jimenez, Christian Li, Lin Lang, Julie Wang, Pin Yu, Min Nat Commun Article Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (TAK1) inhibitor 5Z-7-Oxozeaenol can inhibit TNBC lung metastasis in most animals tested. P38 is a central signal downstream of TAK1 in TNBC cells in TAK1-mediated response to multiple cytokines. Following co-culturing with macrophages or fibroblasts, TNBC cells express interleukin-1 (IL1) or tumor necrosis factor-α (TNFα), respectively. Compared to TAK1 inhibition, suppressing IL1 signaling with recombinant IL1 receptor antagonist (IL1RA) is less efficient in reducing lung metastasis, possibly due to the additional TAK1 signals coming from distinct stromal cells. Together, these observations suggest that TAK1 may play a central role in promoting TNBC cell adaptation to the lung microenvironment by facilitating positive feedback signaling mediated by P38. Approaches targeting the key TAK1-P38 signal could offer a novel means for suppressing TNBC lung metastasis. Nature Publishing Group UK 2018-05-18 /pmc/articles/PMC5959931/ /pubmed/29777109 http://dx.doi.org/10.1038/s41467-018-04460-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Iriondo, Oihana Liu, Yarong Lee, Grace Elhodaky, Mostafa Jimenez, Christian Li, Lin Lang, Julie Wang, Pin Yu, Min TAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis |
title | TAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis |
title_full | TAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis |
title_fullStr | TAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis |
title_full_unstemmed | TAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis |
title_short | TAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis |
title_sort | tak1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959931/ https://www.ncbi.nlm.nih.gov/pubmed/29777109 http://dx.doi.org/10.1038/s41467-018-04460-w |
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