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

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 meta...

Full description

Saved in:

Bibliographic Details
Published in:	British journal of cancer 2013-08, Vol.109 (4), p.994-1003
Main Authors:	DING, J, ZHANG, Z.-M, XIA, Y, LIAO, G.-Q, PAN, Y, LIU, S, ZHANG, Y, YAN, Z.-S
Format:	Article
Language:	eng
Subjects:	Antigens, CD - genetics Antigens, CD - physiology Apoptosis Apoptosis - genetics Biological and medical sciences Cadherins - genetics Cadherins - physiology Cancer research Cell Line, Tumor Cell Proliferation Colonic Neoplasms - genetics Colonic Neoplasms - pathology Colorectal cancer Epigenesis, Genetic Epigenetics Gastroenterology. Liver. Pancreas. Abdomen Gastrointestinal surgery Histone Demethylases - genetics Histone Demethylases - physiology Histones - metabolism HT29 Cells Humans Medical research Medical sciences Metastasis Molecular Diagnostics Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoplasm Invasiveness - genetics Reverse Transcriptase Polymerase Chain Reaction Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumors
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. 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. 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. 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.
ISSN:	0007-0920 1532-1827