E-resources
-
Lin, T; Ponn, A; Hu, X; Law, B K; Lu, J
Oncogene, 09/2010, Volume: 29, Issue: 35Journal Article
Epithelial-mesenchymal transition (EMT) has pivotal roles during embryonic development and carcinoma progression. Members of the Snai1 family of zinc finger transcription factors are central mediators of EMT and induce EMT in part by directly repressing epithelial markers such as E-cadherin, a gatekeeper of the epithelial phenotype and a suppressor of tumor invasion. However, the molecular mechanism underlying Snai1-mediated transcriptional repression remains incompletely understood. Here we show that Snai1 physically interacts with and recruits the histone demethylase LSD1 (KDM1A) to epithelial gene promoters. LSD1 removes dimethylation of lysine 4 on histone H3 (H3K4m2), a covalent histone modification associated with active chromatin. Importantly, LSD1 is essential for Snai1-mediated transcriptional repression and for maintenance of the silenced state of Snai1 target genes in invasive cancer cells. In the absence of LSD1, Snai1 fails to repress E-cadherin. In cancer cells in which E-cadherin is silenced, depletion of LSD1 results in partial de-repression of epithelial genes and elevated H3K4m2 levels at the E-cadherin promoter. These results underline the critical role of LSD1 in Snai1-dependent transcriptional repression of epithelial markers and suggest that the LSD1 complex could be a potential therapeutic target for prevention of EMT-associated tumor invasion.
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.