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WNT5B governs the phenotype of basal-like breast cancer by activating WNT signaling
BACKGROUND: Breast cancer is the leading cause of cancer-related death in women worldwide. Metastatic disease remains the primary cause of death in patients with breast cancer. Basal-like breast cancer (BLBC) is associated with aggressive behavior, stem-like phenotype, high histological grade, poor...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714433/ https://www.ncbi.nlm.nih.gov/pubmed/31462314 http://dx.doi.org/10.1186/s12964-019-0419-2 |
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author | Jiang, Shaojie Zhang, Miaofeng Zhang, Yanhua Zhou, Weiping Zhu, Tao Ruan, Qing Chen, Hui Fang, Jie Zhou, Fei Sun, Jihong Yang, Xiaoming |
author_facet | Jiang, Shaojie Zhang, Miaofeng Zhang, Yanhua Zhou, Weiping Zhu, Tao Ruan, Qing Chen, Hui Fang, Jie Zhou, Fei Sun, Jihong Yang, Xiaoming |
author_sort | Jiang, Shaojie |
collection | PubMed |
description | BACKGROUND: Breast cancer is the leading cause of cancer-related death in women worldwide. Metastatic disease remains the primary cause of death in patients with breast cancer. Basal-like breast cancer (BLBC) is associated with aggressive behavior, stem-like phenotype, high histological grade, poor clinical features, and high rates of recurrences and/or metastasis. However, the mechanism of BLBC phenotype shaping remains obscure. METHODS: Seventeen normal breast/breast cancer cell lines were used for evaluating the breast cancer subtype-markers, WNT targets and constitutive components, and epithelial mesenchymal transition (EMT) markers analysis by western blot. One hundred and twenty formalin-fixed breast cancer tissues were used for immunohistochemistry (IHC) staining. Nine online platforms (cBioPortal, CCLE, GEPIA, etc.) were used for related analyses. RESULTS: We identified Wnt5b as a key regulatory factor that governs the phenotype of BLBC by activating canonical and non-canonical WNT signaling. Wnt5b exhibited basal-like specificity in cells and clinical samples both at the mRNA and protein levels and also showed good correlation with basal-like phenotype at the mRNA level. Besides, Wnt5b was also a promising therapeutic target for LGK-974 treatment. In addition, we identified that CK1α was expressed at low levels in BLBC and that the activation of CK1α by pyrvinium was an alternative strategy for BLBC treatment. CONCLUSIONS: Wnt5b is not only a diagnostic biomarker but also a potential therapeutic target of BLBC. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-019-0419-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6714433 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-67144332019-09-04 WNT5B governs the phenotype of basal-like breast cancer by activating WNT signaling Jiang, Shaojie Zhang, Miaofeng Zhang, Yanhua Zhou, Weiping Zhu, Tao Ruan, Qing Chen, Hui Fang, Jie Zhou, Fei Sun, Jihong Yang, Xiaoming Cell Commun Signal Research BACKGROUND: Breast cancer is the leading cause of cancer-related death in women worldwide. Metastatic disease remains the primary cause of death in patients with breast cancer. Basal-like breast cancer (BLBC) is associated with aggressive behavior, stem-like phenotype, high histological grade, poor clinical features, and high rates of recurrences and/or metastasis. However, the mechanism of BLBC phenotype shaping remains obscure. METHODS: Seventeen normal breast/breast cancer cell lines were used for evaluating the breast cancer subtype-markers, WNT targets and constitutive components, and epithelial mesenchymal transition (EMT) markers analysis by western blot. One hundred and twenty formalin-fixed breast cancer tissues were used for immunohistochemistry (IHC) staining. Nine online platforms (cBioPortal, CCLE, GEPIA, etc.) were used for related analyses. RESULTS: We identified Wnt5b as a key regulatory factor that governs the phenotype of BLBC by activating canonical and non-canonical WNT signaling. Wnt5b exhibited basal-like specificity in cells and clinical samples both at the mRNA and protein levels and also showed good correlation with basal-like phenotype at the mRNA level. Besides, Wnt5b was also a promising therapeutic target for LGK-974 treatment. In addition, we identified that CK1α was expressed at low levels in BLBC and that the activation of CK1α by pyrvinium was an alternative strategy for BLBC treatment. CONCLUSIONS: Wnt5b is not only a diagnostic biomarker but also a potential therapeutic target of BLBC. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-019-0419-2) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-28 /pmc/articles/PMC6714433/ /pubmed/31462314 http://dx.doi.org/10.1186/s12964-019-0419-2 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Jiang, Shaojie Zhang, Miaofeng Zhang, Yanhua Zhou, Weiping Zhu, Tao Ruan, Qing Chen, Hui Fang, Jie Zhou, Fei Sun, Jihong Yang, Xiaoming WNT5B governs the phenotype of basal-like breast cancer by activating WNT signaling |
title | WNT5B governs the phenotype of basal-like breast cancer by activating WNT signaling |
title_full | WNT5B governs the phenotype of basal-like breast cancer by activating WNT signaling |
title_fullStr | WNT5B governs the phenotype of basal-like breast cancer by activating WNT signaling |
title_full_unstemmed | WNT5B governs the phenotype of basal-like breast cancer by activating WNT signaling |
title_short | WNT5B governs the phenotype of basal-like breast cancer by activating WNT signaling |
title_sort | wnt5b governs the phenotype of basal-like breast cancer by activating wnt signaling |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714433/ https://www.ncbi.nlm.nih.gov/pubmed/31462314 http://dx.doi.org/10.1186/s12964-019-0419-2 |
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