Cargando…

CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-κB/SOX4 signaling

Tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and multiple TAM-secreted cytokines have been identified associating with poor clinical outcomes. However, the therapeutic targets existing in the loop between TAMs and cancer cells are...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Neng, Liu, Weiping, Zheng, Yifeng, Wang, Shengqi, Yang, Bowen, Li, Min, Song, Juxian, Zhang, Fengxue, Zhang, Xiaotong, Wang, Qi, Wang, Zhiyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115425/
https://www.ncbi.nlm.nih.gov/pubmed/30158589
http://dx.doi.org/10.1038/s41419-018-0876-3
_version_ 1783351381099282432
author Wang, Neng
Liu, Weiping
Zheng, Yifeng
Wang, Shengqi
Yang, Bowen
Li, Min
Song, Juxian
Zhang, Fengxue
Zhang, Xiaotong
Wang, Qi
Wang, Zhiyu
author_facet Wang, Neng
Liu, Weiping
Zheng, Yifeng
Wang, Shengqi
Yang, Bowen
Li, Min
Song, Juxian
Zhang, Fengxue
Zhang, Xiaotong
Wang, Qi
Wang, Zhiyu
author_sort Wang, Neng
collection PubMed
description Tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and multiple TAM-secreted cytokines have been identified associating with poor clinical outcomes. However, the therapeutic targets existing in the loop between TAMs and cancer cells are still required for further investigation. Here in, cytokine array validated that C-X-C motif chemokine ligand 1 (CXCL1) is the most abundant chemokine secreted by TAMs, and CXCL1 can promote breast cancer migration and invasion ability, as well as epithelial–mesenchymal transition in both mouse and human breast cancer cells. QPCR screening further validated SOX4 as the highest responsive gene following CXCL1 administration. Mechanistic study revealed that CXCL1 binds to SOX4 promoter and activates its transcription via NF-κB pathway. In vivo breast cancer xenografts demonstrated that CXCL1 silencing in TAMs results in a significant reduction in breast cancer growth and metastatic burden. Bioinformatic analysis and clinical investigation finally suggested that high CXCL1 expression is significantly correlated with breast cancer lymph node metastasis, poor overall survival and basal-like subtype. Taken together, our results indicated that TAMs/CXCL1 promotes breast cancer metastasis via NF-κB/SOX4 activation, and CXCL1-based therapy might become a novel strategy for breast cancer metastasis prevention.
format Online
Article
Text
id pubmed-6115425
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-61154252018-08-30 CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-κB/SOX4 signaling Wang, Neng Liu, Weiping Zheng, Yifeng Wang, Shengqi Yang, Bowen Li, Min Song, Juxian Zhang, Fengxue Zhang, Xiaotong Wang, Qi Wang, Zhiyu Cell Death Dis Article Tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and multiple TAM-secreted cytokines have been identified associating with poor clinical outcomes. However, the therapeutic targets existing in the loop between TAMs and cancer cells are still required for further investigation. Here in, cytokine array validated that C-X-C motif chemokine ligand 1 (CXCL1) is the most abundant chemokine secreted by TAMs, and CXCL1 can promote breast cancer migration and invasion ability, as well as epithelial–mesenchymal transition in both mouse and human breast cancer cells. QPCR screening further validated SOX4 as the highest responsive gene following CXCL1 administration. Mechanistic study revealed that CXCL1 binds to SOX4 promoter and activates its transcription via NF-κB pathway. In vivo breast cancer xenografts demonstrated that CXCL1 silencing in TAMs results in a significant reduction in breast cancer growth and metastatic burden. Bioinformatic analysis and clinical investigation finally suggested that high CXCL1 expression is significantly correlated with breast cancer lymph node metastasis, poor overall survival and basal-like subtype. Taken together, our results indicated that TAMs/CXCL1 promotes breast cancer metastasis via NF-κB/SOX4 activation, and CXCL1-based therapy might become a novel strategy for breast cancer metastasis prevention. Nature Publishing Group UK 2018-08-29 /pmc/articles/PMC6115425/ /pubmed/30158589 http://dx.doi.org/10.1038/s41419-018-0876-3 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
Wang, Neng
Liu, Weiping
Zheng, Yifeng
Wang, Shengqi
Yang, Bowen
Li, Min
Song, Juxian
Zhang, Fengxue
Zhang, Xiaotong
Wang, Qi
Wang, Zhiyu
CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-κB/SOX4 signaling
title CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-κB/SOX4 signaling
title_full CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-κB/SOX4 signaling
title_fullStr CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-κB/SOX4 signaling
title_full_unstemmed CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-κB/SOX4 signaling
title_short CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-κB/SOX4 signaling
title_sort cxcl1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating nf-κb/sox4 signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115425/
https://www.ncbi.nlm.nih.gov/pubmed/30158589
http://dx.doi.org/10.1038/s41419-018-0876-3
work_keys_str_mv AT wangneng cxcl1derivedfromtumorassociatedmacrophagespromotesbreastcancermetastasisviaactivatingnfkbsox4signaling
AT liuweiping cxcl1derivedfromtumorassociatedmacrophagespromotesbreastcancermetastasisviaactivatingnfkbsox4signaling
AT zhengyifeng cxcl1derivedfromtumorassociatedmacrophagespromotesbreastcancermetastasisviaactivatingnfkbsox4signaling
AT wangshengqi cxcl1derivedfromtumorassociatedmacrophagespromotesbreastcancermetastasisviaactivatingnfkbsox4signaling
AT yangbowen cxcl1derivedfromtumorassociatedmacrophagespromotesbreastcancermetastasisviaactivatingnfkbsox4signaling
AT limin cxcl1derivedfromtumorassociatedmacrophagespromotesbreastcancermetastasisviaactivatingnfkbsox4signaling
AT songjuxian cxcl1derivedfromtumorassociatedmacrophagespromotesbreastcancermetastasisviaactivatingnfkbsox4signaling
AT zhangfengxue cxcl1derivedfromtumorassociatedmacrophagespromotesbreastcancermetastasisviaactivatingnfkbsox4signaling
AT zhangxiaotong cxcl1derivedfromtumorassociatedmacrophagespromotesbreastcancermetastasisviaactivatingnfkbsox4signaling
AT wangqi cxcl1derivedfromtumorassociatedmacrophagespromotesbreastcancermetastasisviaactivatingnfkbsox4signaling
AT wangzhiyu cxcl1derivedfromtumorassociatedmacrophagespromotesbreastcancermetastasisviaactivatingnfkbsox4signaling