Thymosin ß4 induces proliferation, invasion, and epithelial-to-mesenchymal transition of oral squamous cell carcinoma.

ABSTRACT

The epithelial-to-mesenchymal transition (EMT) plays a vital role in carcinogenesis, invasion, and metastasis of many epithelial tumors including oral squamous cell carcinoma (OSCC), a common malignancy of the head and neck. However, the functional role of the actin-sequestering protein thymosin ß4 (Tß4) in the EMT in OSCCs remains unclear. Thus, we investigated whether overexpression of Tß4 could induce in vitro tumorigenesis such as cell proliferation and anchorage independency and an EMT-like phenotype in OSCCs. Also, we examined whether it affects invasiveness and cell motility-associated signaling molecules. Tß4-overexpressing OSCCs, SCC-15_Tß4 and SCC-25_Tß4, enhanced cell proliferation and colony formation. In addition, we observed that Tß4 overexpression induced an EMT-like phenotype, accompanied by a decrease in expression of the epithelial cell marker E-cadherin and an increase in expression of mesenchymal cell markers vimentin and N-cadherin. Also, the expression level of Twist1, an EMT-inducing transcription factor, was significantly enhanced in SCC-15_Tß4 and SCC-25_Tß4 cells. Tß4 overexpression augmented in vitro invasion and MMP-2 activity and enhanced the phosphorylation of paxillin and cortactin and expression of LIMK1. Taken together, these results suggest that Tß4 overexpression could be one of the causes of tumorigenesis and progression in OSCCs. Further investigation on the Tß4 molecule would encourage the development of specific targets for cancer treatment.