Journal
JOURNAL OF CELL SCIENCE
Volume 122, Issue 7, Pages 1014-1024Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.028241
Keywords
bHLH E2-2; E-cadherin repression; EMT; E47; Snail; Tumour progression; Gene profiling
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Funding
- Spanish Ministry of Education and Science [SAF2004-00361, SAF2007-63051]
- EV [MRTN 2004-005428]
- Consolider-Ingenio [CDC2007-00017]
- EU [MRTN 2004-005428]
- Spanish Ministry of Education and Science
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Functional loss of the cell-cell adhesion molecule E-cadherin is an essential event for epithelial-mesenchymal transition (EMT), a process that allows cell migration during embryonic development and tumour invasion. In most carcinomas, transcriptional repression has emerged as the main mechanism responsible for E-cadherin downregulation. Here, we report the identification of class I bHLH factor E2-2 (TCF4/ITF2) as a new EMT regulator. Both isoforms of E2-2 (E2-2A and E2-2B) induce a full EMT when overexpressed in MDCK cells but without affecting the tumorigenic properties of parental cells, in contrast to other EMT inducers, such as Snail1 or class I bHLH E47. E-cadherin repression mediated by E2-2 is indirect and independent of proximal E-boxes of the promoter. Knockdown studies indicate that E2-2 expression is dispensable for maintenance of the EMT driven by Snail1 and E47. Comparative gene-profiling analysis reveals that E2-2 factors induce similar, yet distinct, genetic programs to that induced by E47 in MDCK cells. These results, together with the embryonic expression pattern of Tcf4 and E2A (which encodes E12/E47), support a distinct role for E2-2 and suggest an interesting interplay between E-cadherin repressors in the regulation of physiological and pathological EMT processes.
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