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Revisiting STAT3 signalling in cancer: new and unexpected biological functions

Hua Yu1, Heehyoung Lee1, Andreas Herrmann1

  • 1Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.

Nature Reviews. Cancer
|October 25, 2014
PubMed

Insights

Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) proteins, especially STAT3, are key targets in cancer therapy. New regulators and functions of JAK-STAT3 signaling in tumors offer novel therapeutic strategies for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Signal Transduction

Background:

  • Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) proteins, particularly STAT3, are critical in cancer development.
  • JAK-STAT3 signaling is implicated in tumor cell proliferation, survival, invasion, and immunosuppression.
  • Emerging evidence links JAK-STAT3 to inflammation, obesity, stem cells, and the pre-metastatic niche.

Purpose of the Study:

  • To highlight the significance of JAK-STAT3 signaling as a therapeutic target in cancer.
  • To review newly identified regulators and functions of JAK-STAT3 in tumor biology.
  • To explore the potential of targeting JAK-STAT3 for novel cancer treatment strategies.

Main Methods:

  • Literature review of recent studies on JAK-STAT signaling in cancer.
  • Analysis of pathways regulating JAK-STAT signaling, including GPCRs, TLRs, and microRNAs.
  • Investigation of STAT3's roles beyond transcription, including mitochondrial function and epigenetics.

Main Results:

  • Multiple pathways including GPCRs, TLRs, and microRNAs regulate JAK-STAT signaling in cancer.
  • STAT3 contributes to cancer progression through proliferation, survival, invasion, immunosuppression, inflammation, obesity, stemness, and pre-metastatic niche formation.
  • STAT3 also influences mitochondrial function and epigenetic gene regulation in cancer cells.

Conclusions:

  • JAK-STAT3 signaling is a multifaceted driver of cancer, with implications beyond its transcriptional role.
  • Newly identified regulators and functions of JAK-STAT3 present promising therapeutic targets.
  • Targeting JAK-STAT3 pathways offers potential for innovative cancer treatment strategies.

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