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First published online March 18, 2009
doi: 10.1242/10.1242/jcs.028241

Journal of Cell Science 122, 1014-1024 (2009)
Published by The Company of Biologists 2009
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Research Article

The class I bHLH factors E2-2A and E2-2B regulate EMT

Verónica R. Sobrado1, Gema Moreno-Bueno1, Eva Cubillo1, Liam J. Holt1,*, M. Angela Nieto2, Francisco Portillo1 and Amparo Cano1,{ddagger}

1 Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas `Alberto Sols' (CSIC-UAM), 28029 Madrid, Spain
2 Instituto de Neurociencias de Alicante, CSIC-UMH, 03550 Sant Joan d'Alacant, Spain

{ddagger} Author for correspondence (e-mail: acano{at}iib.uam.es)

Accepted 1 December 2008

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.

Key words: bHLH E2-2, E-cadherin repression, EMT, E47, Snail, Tumour progression, Gene profiling


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E2-2 factors in EMT

JCS 2009 122: 705. [Full Text]  





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