Abstract
In recent years, signal transducers and activators of transcription (STAT) proteins have been recognized as cytoplasmic transcription factors that mediate extracellular signaling to the nucleus controlling fundamental functions, such as cell proliferation, apoptosis, differentiation, immune responses and angiogenesis. Among them, STAT3 is a major player, aberrant activation of which is involved in several diseases, including cancer. Among other upstream regulators, IL-6/Jak signaling can activate STAT3 and its role appears to be critical in various types of cancer. Although STAT3 has been traditionally recognized as amoncogene, more recently the dual role of STAT3 in cancer, either tumor inductive or suppressive, has been appreciated. The importance and differential effect of STAT3 on tyrosine or serine residues are also a matter of continuing debate. Interestingly, recent findings suggesting that STAT3 plays an important role in cancer stem cell regulation have gained significant attention. This review summarizes current literature focusing on the significance of STAT3 in several diseases as well as in cancer. Understanding the complexity of STAT3 function has the potential to elucidate important molecular aspects of cancer with significant therapeutic implications.
Highlights
signal transducers and activators of transcription (STAT) proteins constitute a large family of transcription factors with a dual role as signal transduction and transcription activators
This study demonstrated that the drug Niclosamide could target IL6-Stat3-AR pathway and overcome enzalutamide resistance, resulting in inhibition of migration and invasion in advanced prostate cancer [114]
A plethora of studies indicate that deregulation of STAT3 pathway is involved in various diseases, including many cancer types, revealing the significance of retaining normal STAT3 signaling for cellular stability
Summary
STAT proteins (signal transducers and activators of transcription) constitute a large family of transcription factors with a dual role as signal transduction and transcription activators. They are found in the cytoplasm in a latent form and become active in response to stimulation by cytokines and growth factors, hormones and peptides. STAT3 is a significant member of STAT family and has been largely studied, in recent years. This review attempts to elucidate the role of STAT3 molecule signaling in occurrence of diseases including cancer
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