The complex roles of STAT3 and STAT5 in maintaining redox balance: Lessons from STAT-mediated xCT expression in cancer cells.

STAT3 and STAT5 mediate diverse cellular processes, transcriptionally regulating gene expression and interacting with cytoplasmic proteins. Their canonical activity is stimulated by cytokines/growth factors through JAK-STAT signaling. As targets of oncogenes with intrinsic tyrosine kinase activity, STAT3 and STAT5 become constitutively active in hematologic neoplasms and solid tumors, promoting cell proliferation and survival and modulating redox homeostasis. This review summarizes reactive oxygen species (ROS)-regulated STAT activation and how STATs influence ROS production. ROS-induced effects on post-translational modifications are presented, and STAT3/5-mediated regulation of xCT, a redox-sensitive target up-regulated in numerous cancers, is discussed with regard to transcriptional cross-talk.