Cancer Cell Biology
Fra-1 regulates vimentin during Ha-RAS-induced epithelial mesenchymal transition in human colon carcinoma cells
Article first published online: 20 DEC 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 122, Issue 8, pages 1745–1756, 15 April 2008
How to Cite
Andreolas, C., Kalogeropoulou, M., Voulgari, A. and Pintzas, A. (2008), Fra-1 regulates vimentin during Ha-RAS-induced epithelial mesenchymal transition in human colon carcinoma cells. Int. J. Cancer, 122: 1745–1756. doi: 10.1002/ijc.23309
- Issue published online: 19 FEB 2008
- Article first published online: 20 DEC 2007
- Manuscript Accepted: 17 OCT 2007
- Manuscript Received: 26 MAY 2007
- EU. Grant Numbers: LSHG-CT-2004-502950, MRTN-CT-2004-50422
- epithelial–mesenchymal transition
The process of epithelial mesenchymal transition, whereby cells acquire molecular alterations and fibroblastic features, is a fundamental process of embryogenesis and cancer invasion/metastasis. The mechanisms responsible for epithelial mesenchymal transition remain elusive. Human tumors frequently establish constitutively activated RAS signaling, which contributes to the malignant phenotype. In an effort to dissect distinct RAS isoform specific functions, we previously established human colon cell lines stably overexpressing activated Harvey-RAS (Ha-RAS) and Kirsten-RAS (Ki-RAS). Using these, we observed that only oncogenic Ha-RAS overexpression resulted in morphologic and molecular changes suggestive of epithelial to mesenchymal transition. We showed that vimentin, a key molecule of epithelial mesenchymal transition, was differentially regulated between Ha-RAS and Ki-RAS leading to a Ha-RAS specific induction of a migrative phenotype and eventually epithelial to mesenchymal transition. We demonstrated that the AP-1 sites in vimentin promoter could be involved in this regulation. A potential role of FRA-1 was suggested in the regulation of vimentin during the Ha-RAS-induced epithelial to mesenchymal transition, in association with colon cell migration. Our results therefore propose that in colon cells, the induction of epithelial mesenchymal transition by oncogenic Ha-RAS could occur through the overexpression of proteins like FRA-1 and vimentin. © 2007 Wiley-Liss, Inc.