TGFβ: A player on multiple fronts in the tumor microenvironment

Abstract

The physiological functions of transforming growth factor (TGF)-β in cell signaling include regulation of developmental processes and cell growth. Tumor cells very often display altered regulation of the TGFβ signaling pathway, either by defects in TGFβ itself or in downstream components of the pathway. TGFβ can play a dual role in tumorigenesis, i.e. it can be either tumor-suppressive or tumor-promoting. TGFβ suppresses the growth of tumor cells; however, in advanced tumors, it is associated with induction of progression, resulting in poor prognosis for patients. The TGFβ negative regulation of cytotoxic cell function, together with the promotion of T-regulatory cell maturation, impairs anti-tumor responses. Recent studies have elucidated new roles for TGFβ signaling in the tumor microenvironment. Abrogation of proper signaling induces epithelial-to-mesenchymal transition with pro-metastatic functions, resulting in cancer progression. Thus, TGFβ signaling in the tumor microenvironment plays an important role in tumor initiation, progression, and metastasis by its capacity to regulate cross-talk between tumor cells and other components of the local environment.