1. ¹Institute of Bioscience and Biotechnology, College of Life Science, National Taiwan Ocean University, Keelung, Taiwan, Republic of China
2. ²Institute of Biopharmaceutical Science, College of Life Science, National Yang-Ming University, Taipei, Taiwan, Republic of China
3. ³Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China

Correspondence: Professor Y Su, Institute of Biopharmaceutical Science, College of Life Science, National Yang-Ming University, Shi-Pai, Taipei 112, Taiwan, Republic of China. E-mail: yeusu@ym.edu.tw

Received 3 May 2006; Revised 4 September 2006; Accepted 11 September 2006; Published online 30 October 2006.

Abstract

The epithelial–mesenchymal transition (EMT) is crucial for the invasion and metastasis of many epithelial tumors including colorectal carcinoma (CRC). In the present study, a scattering and fibroblastic morphology with reduced intercellular contacts was found in the SW480 colon cancer cells overexpressing the gene encoding thymosin 4 (T₄), which was accompanied by a loss of E-cadherin as well as a cytosolic accumulation of -catenin, two most prominent markers of EMT. Whereas E-cadherin downregulation was likely to be accounted by a ZEB1-mediated transcriptional repression, the accumulation of -catenin was a result of glycogen synthase kinase-3 inactivation mediated by integrin-linked kinase (ILK) and/or its downstream effector, Akt. Intriguingly, ILK upregulation in T₄-overexpressing SW480 cells seemed to be attributed mainly to a stabilization of this kinase by complexing with particularly interesting new Cys-His protein (PINCH) more efficiently. In the meantime, a strong correlation between the expression levels of T₄, ILK and E-cadherin in CRC patients was also revealed by immunohistochemical analysis. Taken together, these data suggest a novel role of T₄ in promoting CRC progression by inducing an EMT in tumor cells via upregulating ILK and consequentially its signal transduction.