Transforming growth factor-beta signaling in cancer

Transforming growth factor (TGF-beta) is a multifunctional polypeptide impl icated in the regulation of a variety of cellular processes including growt h, differentiation, apoptosis, adhesion, and motility. Abnormal activation or inhibition of these TGF-beta regulated processes is implicated in many d iseases, including cancer. Cancers can develop through selective exploitati on of defects in TGF-beta signaling that occur at several different levels in the pathway. The TGF-beta signal transduction cascade is initiated when TGF-beta binds to transmembrane receptors. The TGF-beta receptors then phos phorylate and activate Smad proteins, which transduce the signal from the c ytoplasm to the nucleus. In the nucleus, Smads can bind directly to DNA and cooperate with other transcription factors to induce transcription of TGF- beta target genes. Mutations in target genes, Smads, or the TGF-beta recept or are associated with certain human cancers. Microsc. Res. Tech. 52: 363-3 73, 2001. (C) 2001 Wiley-Liss, Inc.