Targeting STAT3 signaling pathway in cancer by agents derived from Mother Nature

Chakrabhavi Dhananjaya Mohan*, Shobith Rangappa, Habbanakuppe D. Preetham, S. Chandra Nayaka, Vijai K. Gupta, Salundi Basappa, Gautam Sethi, Kanchugarakoppal S. Rangappa

*Corresponding author for this work

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalSeminars in Cancer Biology
Early online date20 Apr 2020
DOIs
Publication statusFirst published - 20 Apr 2020
Externally publishedYes

Keywords

  • JAK-STAT signaling
  • Natural compounds
  • Transcription factors
  • Tumorigenesis

Fingerprint Dive into the research topics of 'Targeting STAT3 signaling pathway in cancer by agents derived from Mother Nature'. Together they form a unique fingerprint.

  • Cite this

    Mohan, C. D., Rangappa, S., Preetham, H. D., Chandra Nayaka, S., Gupta, V. K., Basappa, S., Sethi, G., & Rangappa, K. S. (2020). Targeting STAT3 signaling pathway in cancer by agents derived from Mother Nature. Seminars in Cancer Biology. https://doi.org/10.1016/j.semcancer.2020.03.016