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Over-expression of FSIP1 promotes breast cancer progression and confers resistance to docetaxel via MRP1 stabilization

Fibrous sheath-interacting protein 1 (FSIP1) functions centrally in breast carcinogenesis and progression, although its exact role remains to be clarified. Therefore, we sought to establish a correlation between the clinico-pathological features of breast cancer and FSIP1 expression in breast cancer...

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Autores principales: Yan, Meisi, Wang, Jinsong, Ren, Yanlv, Li, Lin, He, Weidan, Zhang, Ying, Liu, Tong, Li, Zhigao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393503/
https://www.ncbi.nlm.nih.gov/pubmed/30814489
http://dx.doi.org/10.1038/s41419-018-1248-8
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author Yan, Meisi
Wang, Jinsong
Ren, Yanlv
Li, Lin
He, Weidan
Zhang, Ying
Liu, Tong
Li, Zhigao
author_facet Yan, Meisi
Wang, Jinsong
Ren, Yanlv
Li, Lin
He, Weidan
Zhang, Ying
Liu, Tong
Li, Zhigao
author_sort Yan, Meisi
collection PubMed
description Fibrous sheath-interacting protein 1 (FSIP1) functions centrally in breast carcinogenesis and progression, although its exact role remains to be clarified. Therefore, we sought to establish a correlation between the clinico-pathological features of breast cancer and FSIP1 expression in breast cancer tissues, as well as to validate its role in tumor progression and chemo-resistance. We analyzed FSIP1 expression in the breast cancer and para-tumor tissues by immunohistochemistry. We performed MTT, Caspase-Glo 3/7 Assay, Annexin V staining, wound healing and trans-well assays to evaluate cellular apoptosis, proliferation, migration and invasion in FSIP1 knockout and wild-type breast cancer cell lines. Additionally, we examined the effects of FSIP1 on docetaxel sensitivity in a nude mice model transplanted with control or FSIP1 knockout breast cancer cells, and also evaluate its role in tumor metastasis. FSIP1 and MRP1 interaction was determined by co-immunoprecipitation and mass spectrometry. We found that breast cancer cells and tissues consistently demonstrated elevated FSIP1 expressions, which correlated with poor overall survival. Notably, patients with high FSIP1 expression in their tumors undergoing docetaxel neoadjuvant chemotherapy had shorter disease-free survival. FSIP1 knockout in breast cancer cells significantly increased their sensitivity to docetaxel both in vitro and in vivo. Mechanistically, FSIP1 bound to the multidrug resistance protein 1 (MRP1) and stabilized it, and knocking out FSIP1 decreased MRP1 expression and increased cellular docetaxel accumulation. In sum, FSIP1 promotes breast carcinogenesis and mediates docetaxel resistance, and may serve as a novel target in the development of breast cancer therapies.
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spelling pubmed-63935032019-02-28 Over-expression of FSIP1 promotes breast cancer progression and confers resistance to docetaxel via MRP1 stabilization Yan, Meisi Wang, Jinsong Ren, Yanlv Li, Lin He, Weidan Zhang, Ying Liu, Tong Li, Zhigao Cell Death Dis Article Fibrous sheath-interacting protein 1 (FSIP1) functions centrally in breast carcinogenesis and progression, although its exact role remains to be clarified. Therefore, we sought to establish a correlation between the clinico-pathological features of breast cancer and FSIP1 expression in breast cancer tissues, as well as to validate its role in tumor progression and chemo-resistance. We analyzed FSIP1 expression in the breast cancer and para-tumor tissues by immunohistochemistry. We performed MTT, Caspase-Glo 3/7 Assay, Annexin V staining, wound healing and trans-well assays to evaluate cellular apoptosis, proliferation, migration and invasion in FSIP1 knockout and wild-type breast cancer cell lines. Additionally, we examined the effects of FSIP1 on docetaxel sensitivity in a nude mice model transplanted with control or FSIP1 knockout breast cancer cells, and also evaluate its role in tumor metastasis. FSIP1 and MRP1 interaction was determined by co-immunoprecipitation and mass spectrometry. We found that breast cancer cells and tissues consistently demonstrated elevated FSIP1 expressions, which correlated with poor overall survival. Notably, patients with high FSIP1 expression in their tumors undergoing docetaxel neoadjuvant chemotherapy had shorter disease-free survival. FSIP1 knockout in breast cancer cells significantly increased their sensitivity to docetaxel both in vitro and in vivo. Mechanistically, FSIP1 bound to the multidrug resistance protein 1 (MRP1) and stabilized it, and knocking out FSIP1 decreased MRP1 expression and increased cellular docetaxel accumulation. In sum, FSIP1 promotes breast carcinogenesis and mediates docetaxel resistance, and may serve as a novel target in the development of breast cancer therapies. Nature Publishing Group UK 2019-02-27 /pmc/articles/PMC6393503/ /pubmed/30814489 http://dx.doi.org/10.1038/s41419-018-1248-8 Text en © The Author(s) 2019 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
Yan, Meisi
Wang, Jinsong
Ren, Yanlv
Li, Lin
He, Weidan
Zhang, Ying
Liu, Tong
Li, Zhigao
Over-expression of FSIP1 promotes breast cancer progression and confers resistance to docetaxel via MRP1 stabilization
title Over-expression of FSIP1 promotes breast cancer progression and confers resistance to docetaxel via MRP1 stabilization
title_full Over-expression of FSIP1 promotes breast cancer progression and confers resistance to docetaxel via MRP1 stabilization
title_fullStr Over-expression of FSIP1 promotes breast cancer progression and confers resistance to docetaxel via MRP1 stabilization
title_full_unstemmed Over-expression of FSIP1 promotes breast cancer progression and confers resistance to docetaxel via MRP1 stabilization
title_short Over-expression of FSIP1 promotes breast cancer progression and confers resistance to docetaxel via MRP1 stabilization
title_sort over-expression of fsip1 promotes breast cancer progression and confers resistance to docetaxel via mrp1 stabilization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393503/
https://www.ncbi.nlm.nih.gov/pubmed/30814489
http://dx.doi.org/10.1038/s41419-018-1248-8
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