Transforming Growth Factor-Beta and Oxidative Stress Interplay: Implications in Tumorigenesis and Cancer Progression

Abstract

Transforming growth factor-beta (TGF-beta) and oxidative stress/ReactiveOxygen Species (ROS) both have pivotal roles in health and disease. In this review we are analyzing the interplay between TGF-beta and ROS in tumorigenesis and cancer progression. They have contradictory roles in cancer progression since both can have antitumor effects, through the induction of cell death, senescence and cell cycle arrest, and protumor effects by contributing to cancer cell spreading, proliferation, survival, and metastasis. TGF-beta can control ROS production directly or by downregulating antioxidative systems. Meanwhile, ROS can influence TGF-beta signaling and increase its expression as well as its activation from the latent complex. This way, both are building a strong interplay which can be taken as an advantage by cancer cells in order to increment their malignancy. In addition, both TGF-beta and ROS are able to induce cell senescence, which in one way protects damaged cells fromneoplastic transformation but alsomay collaborate in cancer progression. The mutual collaboration of TGF-beta and ROS in tumorigenesis is highly complex, and, due to their differential roles in tumor progression, careful consideration should be taken when thinking of combinatorial targeting in cancer therapies.