Journal
SEMINARS IN CANCER BIOLOGY
Volume 80, Issue -, Pages 157-182Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2020.03.016
Keywords
JAK-STAT signaling; Tumorigenesis; Transcription factors; Natural compounds
Categories
Funding
- University Grants Commission, New Delhi
- DST-Promotion of University Research and Scientific (PURSE), Institution of Excellence, University of Mysore
- Department of Biotechnology, Government of India
- National University of Singapore Seed Fund
Ask authors/readers for more resources
Signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor involved in various human malignancies. Its activation promotes tumor progression, while inhibiting STAT3 signaling can effectively suppress tumor growth. This review provides a comprehensive overview of the mechanisms of STAT3 signal transduction, its negative regulators, the role of STAT3 in oncogenesis, and the inhibition of STAT3 signaling by natural compounds with potential anti-tumor activity.
Signal transducer and activator of transcription (STAT) proteins are latent transcription factors that reside in the cytoplasm of several types of cells. In canonical signaling, upon stimulation by cytokines and growth factors, STATs get activated and translocate into the nucleus to transcribe target genes. Among STATs, the STAT3 variant has been studied extensively and implicated in diverse human malignancies. Transcriptionally, STAT3 can upregulate the expression of genes associated with cell proliferation, antiapoptosis, prosurvival, angiogenesis, metastasis, and immune evasion. STAT3 can be constitutively activated in a broad range of human cancers including solid as well as hematological tumors and overexpression of STAT3 has been observed in a wide-range of patient-derived tumor tissue samples that may contribute to dismal prognosis. In contrast, blockade of STAT3 activation using inhibitors or knockdown systems can markedly suppress tumor progression, thus highlighting the significance of abrogating STAT3 signaling cascade in cancer therapy. In this review, we have provided a comprehensive overview of mechanisms of STAT3 signal transduction and its endogenous negative modulators, the role of STAT3 in oncogenesis, the interplay of miRNAs in STAT3 signaling, and mechanisms involved in persistent activation of STAT3. Furthermore, the review also provides a detailed overview of STAT3 signaling inhibition by selected natural compounds, which have displayed potent activity in various preclinical cancer model.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available