Role of TGF-β signaling in tumorigenesis

Abstract

Transforming growth factor β (TGF β) is one of the crucial cytokine playing an important role in developmental and pathological conditions. TGF β is primarily Smad mediated signal transducers but it can also cross talk with c-Jun N-terminal kinases (JNK), Mitogen-activated protein kinases (MAP), Phosphoinositide 3 (PI-3) kinase, Akt/protein kinase B signaling pathways to enhance cancer development. During early stages of cancer the TGF β induces a protective cytostatic effect. In advanced stages, TGF β fails to down regulate Myc, a transcription factor which represses expression of p21Cip1 and p15Ink4b involved proliferation and differentiation of normal epithelial cells and thus losses its cytostatic property. TGF β also involves in various metastatic processes including angiogenesis, extracellular modification, epithelial-mesenchymal transition, cell migration, immune suppression. Several preclinical animal model studies have encouraging outcomes, suggesting TGF β as a potential therapeutic target in advanced cancers.

Keywords

• Venkateshwari A;
• Vinod C;
• Pratibha Nallari A;
• Jyothy A