A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ERα-positive breast cancer cells

The mechanism of estrogen receptor alpha (ERα)-positive breast cancer-associated bone metastasis is poorly understood. In this article, we report that nuclear p21-activated kinase 4 (nPAK4) is a novel repressor of ERα-mediated transactivation in a 17β-estradiol (E2)-dependent manner and promotes PAK...

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Autores principales: Li, Yanshu, Zhang, Hongyan, Zhao, Yue, Wang, Chunyu, Cheng, Zhenguo, Tang, Lina, Gao, Yunling, Liu, Furong, Li, Jiabin, Li, Yan, Li, Yang, Geng, Nanxi, Rui, Xue, Teng, Yuee, Liu, Yunpeng, Cao, Liu, Kumar, Rakesh, Jin, Feng, Li, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367215/
https://www.ncbi.nlm.nih.gov/pubmed/30177834
http://dx.doi.org/10.1038/s41388-018-0456-0
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author Li, Yanshu
Zhang, Hongyan
Zhao, Yue
Wang, Chunyu
Cheng, Zhenguo
Tang, Lina
Gao, Yunling
Liu, Furong
Li, Jiabin
Li, Yan
Li, Yang
Geng, Nanxi
Rui, Xue
Teng, Yuee
Liu, Yunpeng
Cao, Liu
Kumar, Rakesh
Jin, Feng
Li, Feng
author_facet Li, Yanshu
Zhang, Hongyan
Zhao, Yue
Wang, Chunyu
Cheng, Zhenguo
Tang, Lina
Gao, Yunling
Liu, Furong
Li, Jiabin
Li, Yan
Li, Yang
Geng, Nanxi
Rui, Xue
Teng, Yuee
Liu, Yunpeng
Cao, Liu
Kumar, Rakesh
Jin, Feng
Li, Feng
author_sort Li, Yanshu
collection PubMed
description The mechanism of estrogen receptor alpha (ERα)-positive breast cancer-associated bone metastasis is poorly understood. In this article, we report that nuclear p21-activated kinase 4 (nPAK4) is a novel repressor of ERα-mediated transactivation in a 17β-estradiol (E2)-dependent manner and promotes PAK4–ERα axis-mediated bone metastasis by targeting leukemia inhibitory factor receptor (LIFR) in ERα-positive breast cancer. An evaluation of clinical breast cancer samples revealed that nPAK4 is linked to ERα expression and appears to be associated with a poor prognosis in bone metastatic breast cancer. PAK4 bound and co-translocated with ERα from the cytoplasm to the nucleus upon stimulation with E2. nPAK4 enhanced the invasive potential of ERα-positive breast cancer cells in vitro and promoted breast cancer metastasis in vivo. Mechanistically, nPAK4 promoted the metastasis of ERα-positive breast cancer cells by targeting LIFR, a bone metastasis suppressor. Strikingly, the nuclear accumulation of PAK4 might promote aggressive phenotypes, highlighting nPAK4 as a novel predictive biomarker for ERα-positive breast cancer bone metastasis.
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spelling pubmed-63672152019-02-11 A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ERα-positive breast cancer cells Li, Yanshu Zhang, Hongyan Zhao, Yue Wang, Chunyu Cheng, Zhenguo Tang, Lina Gao, Yunling Liu, Furong Li, Jiabin Li, Yan Li, Yang Geng, Nanxi Rui, Xue Teng, Yuee Liu, Yunpeng Cao, Liu Kumar, Rakesh Jin, Feng Li, Feng Oncogene Article The mechanism of estrogen receptor alpha (ERα)-positive breast cancer-associated bone metastasis is poorly understood. In this article, we report that nuclear p21-activated kinase 4 (nPAK4) is a novel repressor of ERα-mediated transactivation in a 17β-estradiol (E2)-dependent manner and promotes PAK4–ERα axis-mediated bone metastasis by targeting leukemia inhibitory factor receptor (LIFR) in ERα-positive breast cancer. An evaluation of clinical breast cancer samples revealed that nPAK4 is linked to ERα expression and appears to be associated with a poor prognosis in bone metastatic breast cancer. PAK4 bound and co-translocated with ERα from the cytoplasm to the nucleus upon stimulation with E2. nPAK4 enhanced the invasive potential of ERα-positive breast cancer cells in vitro and promoted breast cancer metastasis in vivo. Mechanistically, nPAK4 promoted the metastasis of ERα-positive breast cancer cells by targeting LIFR, a bone metastasis suppressor. Strikingly, the nuclear accumulation of PAK4 might promote aggressive phenotypes, highlighting nPAK4 as a novel predictive biomarker for ERα-positive breast cancer bone metastasis. Nature Publishing Group UK 2018-09-03 2019 /pmc/articles/PMC6367215/ /pubmed/30177834 http://dx.doi.org/10.1038/s41388-018-0456-0 Text en © The Author(s) 2018, . This article is published with open access 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
Li, Yanshu
Zhang, Hongyan
Zhao, Yue
Wang, Chunyu
Cheng, Zhenguo
Tang, Lina
Gao, Yunling
Liu, Furong
Li, Jiabin
Li, Yan
Li, Yang
Geng, Nanxi
Rui, Xue
Teng, Yuee
Liu, Yunpeng
Cao, Liu
Kumar, Rakesh
Jin, Feng
Li, Feng
A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ERα-positive breast cancer cells
title A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ERα-positive breast cancer cells
title_full A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ERα-positive breast cancer cells
title_fullStr A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ERα-positive breast cancer cells
title_full_unstemmed A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ERα-positive breast cancer cells
title_short A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ERα-positive breast cancer cells
title_sort mandatory role of nuclear pak4-lifr axis in breast-to-bone metastasis of erα-positive breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367215/
https://www.ncbi.nlm.nih.gov/pubmed/30177834
http://dx.doi.org/10.1038/s41388-018-0456-0
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