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STATs in cancer inflammation and immunity: a leading role for STAT3
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.
The STATs of cancer — new molecular targets come of age
Tumour cells acquire the ability to proliferate uncontrollably, resist apoptosis, sustain angiogenesis and evade immune surveillance. STAT proteins — especially STAT3 and STAT5 — regulate all of…
Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells.
Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis
It is shown that VEGF expression correlates with Stat3 activity in diverse human cancer cell lines and indicates that Stat3 represents a common molecular target for blocking angiogenesis induced by multiple signaling pathways in human cancers.
STATs in oncogenesis
The evidence for critical roles of STATs in oncogenesis is presented and the potential for development of novel cancer therapies based on mechanistic understanding of STAT signaling is discussed.
Revisiting STAT3 signalling in cancer: new and unexpected biological functions
- Hua Yu, Heehyoung Lee, A. Herrmann, R. Buettner, R. Jove
- Biology, MedicineNature Reviews Cancer
- 1 November 2014
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.
Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine…
- M. Blaskovich, Jiazhi Sun, A. Cantor, J. Turkson, R. Jove, S. Sebti
- Biology, ChemistryCancer research
- 15 March 2003
The suppression of phosphotyrosine STAT3 levels resulted in the inhibition of STAT3 DNA binding and STAT3-mediated but not serum response element-mediated gene transcription, giving strong support for pharmacologically targeting the JAK/STAT3 signaling pathway for anticancer drug discovery.
Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity
It is shown that Stat3 is constitutively activated in diverse tumor-infiltrating immune cells, and ablating Stat3 in hematopoietic cells triggers an intrinsic immune-surveillance system that inhibits tumor growth and metastasis.
Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells
It is proposed that tumor Stat-3 activity can mediate immune evasion by blocking both the production and sensing of inflammatory signals by multiple components of the immune system.
Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity
- K. Siddiquee, Shumin M. Zhang, J. Turkson
- Chemistry, BiologyProceedings of the National Academy of Sciences
- 1 May 2007
Findings strongly suggest that the antitumor activity of S3I-201 is mediated in part through inhibition of aberrant Stat3 activation and provide the proof-of-concept for the potential clinical use of Stat3 inhibitors such as S3i-201 in tumors harboring aberrantStat3.