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Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth
BACKGROUND: Our previous study demonstrated that lysine demethylase 2A (KDM2A) enhances stemness in breast cancer cells. This demethylase is also highly expressed in cancer-associated fibroblasts (CAFs). However, its clinical significance is unclear. METHODS: The expression of KDM2A in CAFs was stud...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852571/ https://www.ncbi.nlm.nih.gov/pubmed/33024266 http://dx.doi.org/10.1038/s41416-020-01112-z |
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author | Chen, Jing-Yi Li, Chien-Feng Lai, You-Syuan Hung, Wen-Chun |
author_facet | Chen, Jing-Yi Li, Chien-Feng Lai, You-Syuan Hung, Wen-Chun |
author_sort | Chen, Jing-Yi |
collection | PubMed |
description | BACKGROUND: Our previous study demonstrated that lysine demethylase 2A (KDM2A) enhances stemness in breast cancer cells. This demethylase is also highly expressed in cancer-associated fibroblasts (CAFs). However, its clinical significance is unclear. METHODS: The expression of KDM2A in CAFs was studied using immunohistochemical staining and its association with clinicopathological features and patient’s survival was tested. Overexpression and knockdown strategies were used to investigate KDM2A-regulated genes in fibroblasts. Senescent cells were detected by using β-galactosidase staining. The in vivo tumour-promoting activity of stromal KDM2A was confirmed by animal study. RESULTS: Increase of stromal KDM2A is associated with advanced tumour stage and poor clinical outcome in breast cancer patients. Cancer-derived cytokines stimulated KDM2A expression in normal fibroblasts and transformed them into CAFs. Upregulation of KDM2A induced p53-dependent senescence in fibroblasts and enhanced the release of cytokines, which reciprocally promoted cancer cell proliferation. Additionally, KDM2A upregulated programmed death-ligand 1 (PD-L1) expression via transcriptional activation in fibroblasts. Knockdown of KDM2A completely abolished the tumour-promoting activity of CAFs on breast tumour growth in vivo and diminished PD-L1 expression in the stroma of tumour tissues. CONCLUSIONS: Stromal KDM2A plays an oncogenic role in breast cancer and inhibition of KDM2A reduces fibroblast senescence and suppresses tumour growth. |
format | Online Article Text |
id | pubmed-7852571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78525712021-02-08 Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth Chen, Jing-Yi Li, Chien-Feng Lai, You-Syuan Hung, Wen-Chun Br J Cancer Article BACKGROUND: Our previous study demonstrated that lysine demethylase 2A (KDM2A) enhances stemness in breast cancer cells. This demethylase is also highly expressed in cancer-associated fibroblasts (CAFs). However, its clinical significance is unclear. METHODS: The expression of KDM2A in CAFs was studied using immunohistochemical staining and its association with clinicopathological features and patient’s survival was tested. Overexpression and knockdown strategies were used to investigate KDM2A-regulated genes in fibroblasts. Senescent cells were detected by using β-galactosidase staining. The in vivo tumour-promoting activity of stromal KDM2A was confirmed by animal study. RESULTS: Increase of stromal KDM2A is associated with advanced tumour stage and poor clinical outcome in breast cancer patients. Cancer-derived cytokines stimulated KDM2A expression in normal fibroblasts and transformed them into CAFs. Upregulation of KDM2A induced p53-dependent senescence in fibroblasts and enhanced the release of cytokines, which reciprocally promoted cancer cell proliferation. Additionally, KDM2A upregulated programmed death-ligand 1 (PD-L1) expression via transcriptional activation in fibroblasts. Knockdown of KDM2A completely abolished the tumour-promoting activity of CAFs on breast tumour growth in vivo and diminished PD-L1 expression in the stroma of tumour tissues. CONCLUSIONS: Stromal KDM2A plays an oncogenic role in breast cancer and inhibition of KDM2A reduces fibroblast senescence and suppresses tumour growth. Nature Publishing Group UK 2020-10-07 2021-01-19 /pmc/articles/PMC7852571/ /pubmed/33024266 http://dx.doi.org/10.1038/s41416-020-01112-z Text en © The Author(s) 2020 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 Chen, Jing-Yi Li, Chien-Feng Lai, You-Syuan Hung, Wen-Chun Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth |
title | Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth |
title_full | Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth |
title_fullStr | Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth |
title_full_unstemmed | Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth |
title_short | Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth |
title_sort | lysine demethylase 2a expression in cancer-associated fibroblasts promotes breast tumour growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852571/ https://www.ncbi.nlm.nih.gov/pubmed/33024266 http://dx.doi.org/10.1038/s41416-020-01112-z |
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