JAKs and STATs in chemoresistance
نویسنده
چکیده
Many cancer patients develop resistance to chemotherapeutic drugs and this results in elevated mortality. Understanding the mechanisms that mediate drug resistance is critical to develop novel therapeutic strategies. Fibroblast growth factor (FGF)-2, which leads to the formation of a B-RAF/PKCε/S6K2 multi-protein complex, plays a key role in chemoresistance. This enhances the selective translation of anti-apoptotic proteins such as BCL-2 and IAP family members and protects cells from death induced by chemotherapy in several cancer types. We have been investigating the role of Janus kinases (JAKs) and signal transducers and activators of transcription (STATs), most notably known for their pivotal roles in mediating cytokine and immune responses, in FGF-2-mediated chemoresistance. The participation of JAKs in drug resistance pathways and the implications of using inhibitors to these kinases in cancer multi-target therapies will be discussed.
منابع مشابه
Dysregulation of janus kinases and signal transducers and activators of transcription in cancer.
Despite their long recognised pivotal roles in immunological responses, Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) are now seen as important players in cancer development and progression. Indeed, mutations in the JAKs are often found in myeloproliferative disorders (MPDs) and leukaemia, and the constitutive phosphorylation of STATs is a common occurrence...
متن کاملJaks and stats as therapeutic targets.
Cytokines have critical functions in regulating immune responses. A large number of these factors bind related receptors termed the Type I and Type II families of cytokine receptors. These receptors activate Janus kinases (Jaks) and Stat family of transcription factors. The essential and specific function of Jaks and Stats is particularly well illustrated by human and mouse mutations. The possi...
متن کاملJaks, STATs, Cytokines, and Sepsis.
Sepsis remains a significant cause of morbidity and mortality in the intensive care unit (68), affecting more than 500,000 patients per year in the United States (39). The incidence is increasing despite the major advances in the development of antimicrobial agents and other supportive treatments (56). Septic patients often succumb to a systemic inflammatory response, of which multiple organ fa...
متن کاملRole of the JAK/STAT pathway in rat carotid artery remodeling after vascular injury.
In cultured vascular smooth muscle cells (VSMCs), Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) are expressed constitutively and play a role in angiotensin II (Ang II)-induced intracellular signaling and proliferation. However, little is known regarding the relevance of these proteins to the process of vascular remodeling. The role of JAK and STAT proteins ...
متن کاملBrevilin A, a Novel Natural Product, Inhibits Janus Kinase Activity and Blocks STAT3 Signaling in Cancer Cells
Signal abnormalities in human cells usually cause unexpected consequences for individual health. We focus on these kinds of events involved in JAK-STAT signal pathways, especially the ones triggered by aberrant activated STAT3, an oncoprotein which participates in essential processes of cell survival, growth and proliferation in many types of tumors, as well as immune diseases. By establishing ...
متن کامل