Transforming growth factor-beta signaling in cancer

Abstract

Transforming growth factor (TGF-beta) is a multifunctional polypeptide implicated in the regulation of a variety of cellular processes including growth, differentiation, apoptosis, adhesion, and motility. Abnormal activation or inhibition of these TGF-beta regulated processes is implicated in many diseases, including cancer. Cancers can develop through selective exploitation 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 phosphorylate and activate Smad proteins, which transduce the signal from the cytoplasm 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 receptor are associated with certain human cancers.