LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer
LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer
复制标题
LSD1介导的表观遗传修饰有助于结肠癌的增殖和转移。
DOI：
10.1038/bjc.2013.364
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发表时间：
2013-08-20
影响因子：
8.8
通讯作者：
Yan, Z-S
中科院分区：
文献类型：
--
作者：
Ding, J.;Zhang, Z-M;Yan, Z-S
背景资料：赖氨酸特异性脱甲基酶1（LSD 1）在肿瘤的发生、增殖和转移等过程中发挥重要作用。本研究旨在探讨LSD 1在结肠癌细胞增殖和转移中的作用及其分子机制。方法：研究LSD 1、CDH-1和CDH-2与结肠癌细胞侵袭能力的关系，并探讨LSD 1在结肠癌细胞增殖、侵袭和凋亡中的作用。结果：LSD 1在结肠癌组织中表达上调，LSD 1的高表达与肿瘤的TNM分期和远处转移密切相关。在功能上，LSD 1的抑制损害增殖和侵袭力，并在体外诱导结肠癌细胞凋亡。结论：LSD 1通过表观遗传修饰下调CDH-1的表达，促进结肠癌细胞的转移。LSD 1拮抗剂可能是抑制结肠癌转移的有效策略。
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.