AUTHOR=Zhang Qiang , Yu Nengwang , Lee Chung 

TITLE=Mysteries of TGF-β Paradox in Benign and Malignant Cells

JOURNAL=Frontiers in Oncology

VOLUME=Volume 4 - 2014

YEAR=2014

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2014.00094

DOI=10.3389/fonc.2014.00094

ISSN=2234-943X

ABSTRACT=TGF-β regulates a wide range of biological functions including embryonic development, wound healing, organogenesis, immune modulation, and cancer progression. Interestingly, TGF-β is known to inhibit cell growth in benign cells but promote progression in cancer cells, a phenomenon known as TGF-β paradox. To date, the mechanism of this paradox still remains as a scientific mystery. In this review, we present our experience, alone with the literature, in an attempt to offer answers to this mystery. First, we observed that, upon TGF-β engagement, there is a differential activation of Erk between benign and cancer cells. Since activated Erk is a major mediator in tumor progression and metastasis, a differentially activated Erk represents the answer to this mystery. Second, we identified a key player, PP2A-B56α, which is differentially recruited by the activated type I TGF-β receptor (TBRI) in benign and tumor cells, resulting in differential Erk activation. Finally, TGF-β stimulation leads to a suppressed TBRs in tumor cells but not in benign cells. This differentially suppressed TBRs triggers differential recruitment of PP2A-B56α and, thus, differential activation of Erk. The above three events offer the explanation to the mysteries