Abstract
Signal transducer and activator of transcription 3 (STAT3), a member of the STAT protein family, can be phosphorylated by receptor-associated Janus kinases (JAKs) in response to stimulation by cytokines and growth factors. It forms homo- or heterodimers that can translocate to the cell nucleus where they act as transcription activators. Constitutive activation of STAT3 has been found to be associated with initiation and progression of various cancers. It can exert proliferative as well as anti-apoptotic effects. This review focuses on the role of STAT3 in pathogenesis i.e., proliferation, differentiation, migration, and apoptosis of hematological malignancies viz. leukemia, lymphoma and myeloma, and briefly highlights the potential therapeutic approaches developed against STAT3 activation pathway.
Highlights
Signal Transducers and Activators of Transcription (STATs), were first discovered in 1994 and found to be involved in interferon (IFN)-triggered transcription regulation [1,2,3]
Constitutive phosphorylation and activation of STATs have been found in several leukemias [38,39] including AML [40], acute promyelocytic leukemia [41], acute lymphoblastic leukemia (ALL) [42], chronic lymphocytic leukemia (CLL) [43], and chronic myelogenous leukemia (CML) [40]
In 2014, Shastri et al revealed that patients with increased Signal transducer and activator of transcription 3 (STAT3) expression in hematopoietic stem cells (HSCs) were associated with a median survival of 2.6 years, while patients with lower STAT3 expression were observed to have a median survival of 5.8 years [47]
Summary
Signal Transducers and Activators of Transcription (STATs), were first discovered in 1994 and found to be involved in interferon (IFN)-triggered transcription regulation [1,2,3]. The STAT family proteins transduce intracellular and extracellular signals that mediate multiple cellular functions including those related to survival, growth and proliferation, and angiogenesis [6,7]. STAT family members are generally localized in the cytoplasmic compartment of the cell, in an inactive state, either as monomers or as latent (unphosphorylated) dimers [8] that can be activated by various stimuli such as cytokines and growth factors [9,10,11]. STATs are activated by phosphorylation on tyrosine by Janus kinases (JAKs), Src family members, as well as growth factor. Cancers 2018, 10, 327 receptors such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR). (EGFR) and platelet-derived growth factor receptor (PDGFR) [1,10,12].
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