TGF-β1 inhibits the growth and metastasis of tongue squamous carcinoma cells through Smad4

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine that regulates cell growth, differentiation, migration, apoptosis and extracellular matrix remodeling. TGF-beta 1 transduces signals from the cell membrane to the cell nucleus through serine/threonine kinase receptors and their downstream effectors, Smad molecules. Although many studies have been focused on TGF-beta 1-Smad signaling pathway, the role of TGF-beta 1/Smad in tongue squamous cell carcinoma is not fully understood. In the present study, we used a series of cell function assays to examine the role of TGF-beta-Smad4 signaling in tongue squamous cell carcinoma. We observed the effects of TGF-beta 1 on the growth and metastatic potential of the tongue squamous cell carcinoma cell line Ts, which expresses lower level of Smad4 protein. We found that Smad4 could decrease TGF-beta 1-induced cell proliferation, and that Smad4 overexpression promoted Ts cell apoptosis. In Ts vector control cells, TGF-beta 1 increased the expression of T beta RII, as well as MMP-2, and enhanced cell invasion through the basement membrane, and then induced cell metastasis. However in Ts cells stably expressing Smad4. Smad4 mediated TGF-beta 1-induced p21 expression promoted cell apoptosis and inhibited cell proliferation, delayed MMP-2 expression, and decreased cell metastasis. Therefore, TGF-beta 1 plays distinct roles in the Smad4-dependent and -independent signaling pathways. (C) 2011 Elsevier B.V. All rights reserved.