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 β4 (Tβ4), which was accompanied by a loss of E-cadherin as well as a cytosolic accumulation of β-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 β-catenin was a result of glycogen synthase kinase-3β inactivation mediated by integrin-linked kinase (ILK) and/or its downstream effector, Akt. Intriguingly, ILK upregulation in Tβ4-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 Tβ4, ILK and E-cadherin in CRC patients was also revealed by immunohistochemical analysis. Taken together, these data suggest a novel role of Tβ4 in promoting CRC progression by inducing an EMT in tumor cells via upregulating ILK and consequentially its signal transduction.
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Acknowledgements
This study was supported by Grants NSC 94-2320-B-010-050 and NSC 95-2320-B-010-043-MY3 from National Science Council and 95A-C-D01-PPG-03 from the Ministry of Education, Aim for the Top University Plan, of the Republic of China. We thank Ms Yi-Ting Shen for preparing the recombinant adenovirus that expresses Tβ4 antisense RNA.
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Huang, HC., Hu, CH., Tang, MC. et al. Thymosin β4 triggers an epithelial–mesenchymal transition in colorectal carcinoma by upregulating integrin-linked kinase. Oncogene 26, 2781–2790 (2007). https://doi.org/10.1038/sj.onc.1210078
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DOI: https://doi.org/10.1038/sj.onc.1210078
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