The role of TGF beta in human cancers

Transforming growth factor beta (TGF beta) is secreted as a large latent pr ecursor from both normal and transformed cells which needs to be activated for biological activity. The active TGF beta binds either directly to T bet aR-II or indirectly by binding to beta -glycan which then presents the TGF beta to T betaR-II. Formation of the TGF beta -T betaR-II complex rapidly l eads to phosphorylation of T betaR-I. T betaR-I, in turn, phosphorylates re ceptor-specific Smads and induces their translocation into the nucleus. TGF beta is able to act as a growth stimulator or inhibitor and elicits a broa d spectrum of biological effects on various cell types. However, these cell s may lose their sensitivity and responsiveness to TGF beta. Down-regulatio n or loss of functional receptors, aberrant signal transduction pathways du e to Smad mutations, loss of the cell's ability to activate latent TGF beta , loss of the peptide itself or functional genes that control the transcrip tion and translation of TGF beta may contribute to development of cancer.