The Dominant Role of Forkhead Box Proteins in Cancer

Forkhead box (FOX) proteins are multifaceted transcription factors that are significantly implicated in cancer, with various critical roles in biological processes. Herein, we provide an overview of several key members of the FOXA, FOXC, FOXM1, FOXO and FOXP subfamilies. Important pathophysiological processes of FOX transcription factors at multiple levels in a context-dependent manner are discussed. We also specifically summarize some major aspects of FOX transcription factors in association with cancer research such as drug resistance, tumor growth, genomic alterations or drivers of initiation. Finally, we suggest that targeting FOX proteins may be a potential therapeutic strategy to combat cancer.

PPAR and Oxidative Stress: Con() Catenating NRF2 and FOXO

Peroxisome-proliferator activator receptorγ(PPARγ) is a nuclear receptor of central importance in energy homeostasis and inflammation. Recent experimental pieces of evidence demonstrate that PPARγis implicated in the oxidative stress response, an imbalance between antithetic prooxidation and antioxidation forces that may lead the cell to apoptotic or necrotic death. In this delicate and intricate game of equilibrium, PPARγstands out as a central player devoted to the quenching and containment of the damage and to foster cell survival. However, PPARγdoes not act alone: indeed the nuclear receptor is at the point of interconnection of various pathways, such as the nuclear factor erythroid 2-related factor 2 (NRF2), Wnt/β-catenin, and forkhead box proteins O (FOXO) pathways. Here we reviewed the role of PPARγin response to oxidative stress and its interaction with other signaling pathways implicated in this process, an interaction that emerged as a potential new therapeutic target for several oxidative-related diseases.