STAT3 and STAT5 Activation in Solid Cancers
1
Department of Biochemistry and Molecular Medicine, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, QC, H3C 3J7, Canada
2
CRCHUM, 900 Saint-Denis St, Montréal, QC H2X 0A9, Canada
3
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna 1210, Austria
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(10), 1428; https://doi.org/10.3390/cancers11101428
Received: 1 August 2019 / Revised: 14 September 2019 / Accepted: 18 September 2019 / Published: 25 September 2019
(This article belongs to the Special Issue Targeting STAT3 and STAT5 in Cancer)
The Signal Transducer and Activator of Transcription (STAT)3 and 5 proteins are activated by many cytokine receptors to regulate specific gene expression and mitochondrial functions. Their role in cancer is largely context-dependent as they can both act as oncogenes and tumor suppressors. We review here the role of STAT3/5 activation in solid cancers and summarize their association with survival in cancer patients. The molecular mechanisms that underpin the oncogenic activity of STAT3/5 signaling include the regulation of genes that control cell cycle and cell death. However, recent advances also highlight the critical role of STAT3/5 target genes mediating inflammation and stemness. In addition, STAT3 mitochondrial functions are required for transformation. On the other hand, several tumor suppressor pathways act on or are activated by STAT3/5 signaling, including tyrosine phosphatases, the sumo ligase Protein Inhibitor of Activated STAT3 (PIAS3), the E3 ubiquitin ligase TATA Element Modulatory Factor/Androgen Receptor-Coactivator of 160 kDa (TMF/ARA160), the miRNAs miR-124 and miR-1181, the Protein of alternative reading frame 19 (p19ARF)/p53 pathway and the Suppressor of Cytokine Signaling 1 and 3 (SOCS1/3) proteins. Cancer mutations and epigenetic alterations may alter the balance between pro-oncogenic and tumor suppressor activities associated with STAT3/5 signaling, explaining their context-dependent association with tumor progression both in human cancers and animal models.
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Keywords:
solid cancers; cell cycle; apoptosis; inflammation; mitochondria; stemness; tumor suppression
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MDPI and ACS Style
Igelmann, S.; Neubauer, H.A.; Ferbeyre, G. STAT3 and STAT5 Activation in Solid Cancers. Cancers 2019, 11, 1428. https://doi.org/10.3390/cancers11101428
AMA Style
Igelmann S, Neubauer HA, Ferbeyre G. STAT3 and STAT5 Activation in Solid Cancers. Cancers. 2019; 11(10):1428. https://doi.org/10.3390/cancers11101428
Chicago/Turabian StyleIgelmann, Sebastian; Neubauer, Heidi A.; Ferbeyre, Gerardo. 2019. "STAT3 and STAT5 Activation in Solid Cancers" Cancers 11, no. 10: 1428. https://doi.org/10.3390/cancers11101428
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