Thymosin ?4 Regulates Focal Adhesion Formation in Human Melanoma Cells and Affects Their Migration and Invasion.

ABSTRACT: Thymosin ?4 (T?4), a multifunctional 44-amino acid polypeptide and a member of actin-binding proteins (ABPs), plays an important role in developmental processes and wound healing. In recent years an increasing number of data has been published suggesting T?4's involvement in tumorigenesis. However, T?4's role in melanoma tumor development still remains to be elucidated. In our study we demonstrate that T?4 is crucial for melanoma adhesion and invasion. For the purpose of our research we tested melanoma cell lines differing in invasive potential. Moreover, we applied shRNAs to silence TMSB4X (gene encoding T?4) expression in a cell line with high TMSB4X expression. We found out that T?4 is not only a component of focal adhesions (FAs) and interacts with several FAs components but also regulates FAs formation. We demonstrate that T?4 level has an impact on FAs' number and morphology. Moreover, manipulation with TMSB4X expression resulted in changes in cells' motility on non-coated and MatrigelTM (resembling basement membrane composition)-coated surfaces and drastically decreased invasion abilities of the cells. Additionally, a correlation between T?4 expression level and exhibition of mesenchymal-like [epithelial-mesenchymal transition (EMT)] features was discovered. Cells with lowered TMSB4X expression were less EMT-progressed than control cells. Summarizing, obtained results show that T?4 by regulating melanoma cells' adhesion has an impact on motility features and EMT. Our study not only contributes to a better understanding of the processes underlying melanoma cells' capacity to create metastases but also highlights T?4 as a potential target for melanoma management therapy.

SUBMITTER: Makowiecka A 

PROVIDER: S-EPMC6935720 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature