Thymosin β-4 (Tβ-4), a small peptide originally isolated from calf thymus, modulates the formation of F-actin microfilaments by sequestering the monomeric G-actin. Recent studies have shown that overexpression of the Tβ-4 gene occurs not only in many human carcinomas but also in the highly metastatic melanomas and fibrosarcomas. However, little is known about the specific growth advantages acquired by different tumors from this genetic abnormality. To address the above questions, Tβ-4-overexpressing human colon carcinoma (SW480) cells were established by stable transfection and their phenotypic changes were monitored. We found that both the morphology and the cortical actin cytoskeleton of SW480 cells were altered by Tβ-4 overexpression. Moreover, both cellular level and that distributed over the intercellular junctions of the E-cadherin were decreased in the Tβ-4 overexpressers, which were accompanied by a twofold increase in their saturation densities. Meanwhile, these cells also exhibited an increased ability to form colonies in soft agar. Interestingly, a dramatic increase of growth rate was detected in the Tβ-4 overexpressers, which might be attributed to an accelerated proliferation induced by c-Myc that was activated by nuclear β-catenin. Finally, a motility increase of these cells was demonstrated by two independent migration assays, which was accompanied by an enhanced focal contact. Taken together, our data suggest that the drastic growth property and motility changes of the SW480 cells overexpressing Tβ-4 gene are due mainly to a deregulated cell–cell adhesion arisen from the downregulation of E-cadherin, plus uncontrolled cell proliferation owing to the upregulation of β-catenin, both resulted from a breakdown of actin microfilaments caused by the overexpression of this G-actin sequestering peptide.
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This study was supported in part by Grants NSC 89-2320-B-010-126 and NSC 90-2314-B-075-080 from the Nation Science Council and in part by the Grant 89-B-FA22-2-4 (Program for Promoting Academic Excellence of Universities) of the Republic of China.
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Wang, WS., Chen, PM., Hsiao, HL. et al. Overexpression of the thymosin β-4 gene is associated with malignant progression of SW480 colon cancer cells. Oncogene 22, 3297–3306 (2003). https://doi.org/10.1038/sj.onc.1206404
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