Targeted therapy of epigenomic regulatory mechanisms controlling the epithelial to mesenchymal transition during tumor progression

被引:13
作者
Mishra, Vivek Kumar [1 ]
Johnsen, Steven A. [1 ]
机构
[1] Univ Med Ctr Gottingen, Dept Gen Visceral & Pediat Surg, D-37075 Gottingen, Germany
关键词
Epithelial-to-mesenchymal transition; Mesenchymal-to-epithelial transition; Cancer metastasis; Epigenomic regulation; Epigenomic modifiers; Transcription factors; Chromatin structure; E-CADHERIN EXPRESSION; HISTONE DEACETYLASE INHIBITOR; ACUTE MYELOID-LEUKEMIA; CANCER CELL-LINES; DNA METHYLTRANSFERASE INHIBITORS; TRANSCRIPTION FACTOR SNAIL; PHASE-I TRIAL; BREAST-CANCER; STEM-CELLS; METHYLATION PATTERNS;
D O I
10.1007/s00441-014-1912-y
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The epithelial-to-mesenchymal transition (EMT) is a reversible change in cell phenotype that plays a crucial role during normal development and cancer metastasis. EMT imparts embryonic epithelial cells with the ability to migrate and to give rise to organs or tissues at distant sites. During cancer progression, the same developmental process is utilized in an analogous manner to enable cancer cells to move to distant organs and form metastases. The reversion of EMT via the mesenchymal-to-epithelial transition (MET) appears to be required for the formation of secondary tumors at distal sites. The plasticity of epigenomic modifications that control the transcriptional program of cells enables cells to switch back and forth from epithelial and mesenchymal phenotypes during these transitions. Here, we review the interplay between complex epigenomic regulatory mechanisms and various transcription factors involved in EMT leading to changes in gene expression and cell phenotype. We also discuss the way that a deeper understanding of the epigenomic regulation of EMT might shed light onto the process of cancer progression and reveal new targets for novel and more specific anticancer epigenomic therapies.
引用
收藏
页码:617 / 630
页数:14
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