The class I bHLH factors E2-2A and E2-2B regulate EMT
Author:
Sobrado Verónica R.1, Moreno-Bueno Gema1, Cubillo Eva1, Holt Liam J.1, Nieto M. Angela2, Portillo Francisco1, Cano Amparo1
Affiliation:
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
Abstract
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.
Publisher
The Company of Biologists
Reference59 articles.
1. Aigner, K., Dampier, B., Descovich, L., Mikula, M., Sultan, A., Schreiber, M., Mikulits, W., Brabletz, T., Strand, D., Obrist, P. et al. (2007). The transcription factor ZEB1 (δEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Oncogene26, 6979-6988. 2. Batlle, E., Sancho, E., Franci, C., Domínguez, D., Monfar, M., Baulida, J. and Garcia De Herreros, A. (2000). The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat. Cell Biol.2, 84-89. 3. Bayly, R., Chuen, L., Currie, R. A., Hyndman, B. D., Casselman, R., Blobel, G. A. and LeBrun, D. P. (2004). E2A-PBX1 interacts directly with the KIX domain of CBP/p300 in the induction of proliferation in primary hematopoietic cells. J. Biol. Chem.279, 55362-55371. 4. Bergvist, I., Eriksson, M., Saarikettu, J., Eriksson, B., Corneliussen, B., Grundstrom, T. and Holmberg, D. (2000). The basic helix-loop-helix transcription factor E2-2 is involved in T lymphocyte development. Eur. J. Immunol.30, 2857-2863. 5. Birchmeier, W. and Behrens, J. (1994). Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim. Biophys. Acta1198, 11-26.
Cited by
104 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|