Cancers, Vol. 10, Pages 359: The Cooperative Relationship between STAT5 and Reactive Oxygen Species in Leukemia: Mechanism and Therapeutic Potential

Cancers, Vol. 10, Pages 359: The Cooperative Relationship between STAT5 and Reactive Oxygen Species in Leukemia: Mechanism and Therapeutic Potential Cancers doi: 10.3390/cancers10100359 Authors: Tian Mi Zhengqi Wang Kevin D. Bunting Reactive oxygen species (ROS) are now recognized as important second messengers with roles in many aspects of signaling during leukemogenesis. They serve as critical cell signaling molecules that regulate the activity of various enzymes including tyrosine phosphatases. ROS can induce inactivation of tyrosine phosphatases, which counteract the effects of tyrosine kinases. ROS increase phosphorylation of many proteins including signal transducer and activator of transcription-5 (STAT5) via Janus kinases (JAKs). STAT5 is aberrantly activated through phosphorylation in many types of cancer and this constitutive activation is associated with cell survival, proliferation, and self-renewal. Such leukemic activation of STAT5 is rarely caused by mutation of the STAT5 gene itself but instead by overactive mutant receptors with tyrosine kinase activity as well as JAK, SRC family protein tyrosine kinases (SFKs), and Abelson murine leukemia viral oncogene homolog (ABL) kinases. Interestingly, STAT5 suppresses transcription of several genes encoding antioxidant enzymes while simultaneously enhancing transcription of NADPH oxidase. By doing so, STAT5 activation promotes an overall elevation of ROS level, which acts as a feed-forward loop, especially ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research