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LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer

BACKGROUND: Emerging evidence has demonstrated that lysine-specific demethylase 1 (LSD1) has an important role in many pathological processes of cancer cells, such as carcinogenesis, proliferation and metastasis. In this study, we characterised the role and molecular mechanisms of LSD1 in proliferat...

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Autores principales: Ding, J, Zhang, Z-M, Xia, Y, Liao, G-Q, Pan, Y, Liu, S, Zhang, Y, Yan, Z-S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749561/
https://www.ncbi.nlm.nih.gov/pubmed/23900215
http://dx.doi.org/10.1038/bjc.2013.364
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author Ding, J
Zhang, Z-M
Xia, Y
Liao, G-Q
Pan, Y
Liu, S
Zhang, Y
Yan, Z-S
author_facet Ding, J
Zhang, Z-M
Xia, Y
Liao, G-Q
Pan, Y
Liu, S
Zhang, Y
Yan, Z-S
author_sort Ding, J
collection PubMed
description BACKGROUND: Emerging evidence has demonstrated that lysine-specific demethylase 1 (LSD1) has an important role in many pathological processes of cancer cells, such as carcinogenesis, proliferation and metastasis. In this study, we characterised the role and molecular mechanisms of LSD1 in proliferation and metastasis of colon cancer. METHODS: We evaluated the correlation of LSD1, CDH-1 and CDH-2 with invasiveness of colon cancer cells, and investigated the roles of LSD1 in proliferation, invasion and apoptosis of colon cancer cells. We further investigated the mechanisms of LSD1-mediated metastasis of colon cancer. RESULTS: Lysine-specific demethylase 1 was upregulated in colon cancer tissues, and the high LSD1 expression was significantly associated with tumour-node-metastasis (TNM) stages and distant metastasis. Functionally, inhibition of LSD1 impaired proliferation and invasiveness, and induced apoptosis of colon cancer cells in vitro. The LSD1 physically interacted with the promoter of CDH-1 and decreased dimethyl histone H3 lysine 4 (H3K4) at this region, downregulated CDH-1 expression, and consequently contributed to colon cancer metastasis. CONCLUSION: Lysine-specific demethylase 1 downregulates the expression of CDH-1 by epigenetic modification, and consequently promotes metastasis of colon cancer cells. The LSD1 antagonists might be a useful strategy to suppress metastasis of colon cancer.
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spelling pubmed-37495612014-08-20 LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer Ding, J Zhang, Z-M Xia, Y Liao, G-Q Pan, Y Liu, S Zhang, Y Yan, Z-S Br J Cancer Molecular Diagnostics BACKGROUND: Emerging evidence has demonstrated that lysine-specific demethylase 1 (LSD1) has an important role in many pathological processes of cancer cells, such as carcinogenesis, proliferation and metastasis. In this study, we characterised the role and molecular mechanisms of LSD1 in proliferation and metastasis of colon cancer. METHODS: We evaluated the correlation of LSD1, CDH-1 and CDH-2 with invasiveness of colon cancer cells, and investigated the roles of LSD1 in proliferation, invasion and apoptosis of colon cancer cells. We further investigated the mechanisms of LSD1-mediated metastasis of colon cancer. RESULTS: Lysine-specific demethylase 1 was upregulated in colon cancer tissues, and the high LSD1 expression was significantly associated with tumour-node-metastasis (TNM) stages and distant metastasis. Functionally, inhibition of LSD1 impaired proliferation and invasiveness, and induced apoptosis of colon cancer cells in vitro. The LSD1 physically interacted with the promoter of CDH-1 and decreased dimethyl histone H3 lysine 4 (H3K4) at this region, downregulated CDH-1 expression, and consequently contributed to colon cancer metastasis. CONCLUSION: Lysine-specific demethylase 1 downregulates the expression of CDH-1 by epigenetic modification, and consequently promotes metastasis of colon cancer cells. The LSD1 antagonists might be a useful strategy to suppress metastasis of colon cancer. Nature Publishing Group 2013-08-20 2013-07-30 /pmc/articles/PMC3749561/ /pubmed/23900215 http://dx.doi.org/10.1038/bjc.2013.364 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Molecular Diagnostics
Ding, J
Zhang, Z-M
Xia, Y
Liao, G-Q
Pan, Y
Liu, S
Zhang, Y
Yan, Z-S
LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer
title LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer
title_full LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer
title_fullStr LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer
title_full_unstemmed LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer
title_short LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer
title_sort lsd1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749561/
https://www.ncbi.nlm.nih.gov/pubmed/23900215
http://dx.doi.org/10.1038/bjc.2013.364
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