TGF-beta signaling in cancer--a double-edged sword

Abstract

Transforming growth factor (TGF) beta1 is a potent growth inhibitor, with tumor-suppressing activity. Cancers are often refractile to this growth inhibition either because of genetic loss of TGF-beta signaling components or, more commonly, because of downstream perturbation of the signaling pathway, such as by Ras activation. Carcinomas often secrete excess TGF-beta1 and respond to it by enhanced invasion and metastasis. Therapeutic approaches should aim to inhibit the TGF-beta-induced invasive phenotype, but also to retain its growth-inhibitory and apoptosis-inducing effects.