TGFβ: A player on multiple fronts in the tumor microenvironment

The physiological functions of transforming growth factor (TGF)-beta in cell signaling include regulation of developmental processes and cell growth. Tumor cells very often display altered regulation of the TGF beta signaling pathway, either by defects in TGF beta itself or in downstream components of the pathway. TGF beta can play a dual role in tumorigenesis, i.e. it can be either tumor-suppressive or tumor-promoting. TGF beta suppresses the growth of tumor cells; however, in advanced tumors, it is associated with induction of progression, resulting in poor prognosis for patients. The TGF beta 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 TGF beta signaling in the tumor microenvironment. Abrogation of proper signaling induces epithelial-to-mesenchymal transition with pro-metastatic functions, resulting in cancer progression. Thus, TGF beta 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.