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Journal ArticleDOI

Revisiting STAT3 signalling in cancer: new and unexpected biological functions

TLDR
Well known for its role in tumour cell proliferation, survival, invasion and immunosuppression, JAK–STAT3 signalling also promotes cancer through inflammation, obesity, stem cells and the pre-metastatic niche.
Abstract
The Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) proteins, particularly STAT3, are among the most promising new targets for cancer therapy. In addition to interleukin-6 (IL-6) and its family members, multiple pathways, including G-protein-coupled receptors (GPCRs), Toll-like receptors (TLRs) and microRNAs were recently identified to regulate JAK-STAT signalling in cancer. Well known for its role in tumour cell proliferation, survival, invasion and immunosuppression, JAK-STAT3 signalling also promotes cancer through inflammation, obesity, stem cells and the pre-metastatic niche. In addition to its established role as a transcription factor in cancer, STAT3 regulates mitochondrion functions, as well as gene expression through epigenetic mechanisms. Newly identified regulators and functions of JAK-STAT3 in tumours are important targets for potential therapeutic strategies in the treatment of cancer.

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Journal ArticleDOI

Macrophages and Therapeutic Resistance in Cancer

TL;DR: This review discusses the molecular/cellular pathways identified so far whereby macrophages mediate therapeutic responses and therapeutics impacting macrophage presence and/or bioactivity have shown promise in preclinical models and are now being evaluated in the clinic.
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Therapeutic cancer vaccines

TL;DR: The clinical benefit of therapeutic cancer vaccines has been established and the specificity of therapeutic vaccination combined with such immunomodulation offers an attractive avenue for the development of future cancer therapies.
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Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer

TL;DR: The key roles of the IL-6 cytokine family in regulating innate and adaptive immunity, as well as other physiological responses are considered, which highlight the potential of targeting IL- 6 family members to treat inflammatory diseases and cancer.
References
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Journal ArticleDOI

Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell

TL;DR: It is demonstrated that the cell capable of initiating human AML in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice) — termed the SCID leukemia-initiating cell, or SL-IC — possesses the differentiate and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell.
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Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins

TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
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A cell initiating human acute myeloid leukaemia after transplantation into SCID mice

TL;DR: This in vivo model replicates many aspects of human AML and defines a new leukaemia-initiating cell which is less mature than colony-forming cells.
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How cells respond to interferons

TL;DR: The Janus kinases and signal transducers and activators of transcription, and many of the interferon-induced proteins, play important alternative roles in cells, raising interesting questions as to how the responses to the interFERons intersect with more general aspects of cellular physiology and how the specificity of cytokine responses is maintained.
Journal ArticleDOI

STATs in cancer inflammation and immunity: a leading role for STAT3

TL;DR: Signal transducer and activator of transcription proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer, and STAT3 is a promising target to redirect inflammation for cancer therapy.
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