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Sirtuin-1 Activation Controls Tumor Growth by Impeding Th17 Differentiation via STAT3 Deacetylation
- Source :
- Cell Reports, Vol 19, Iss 4, Pp 746-759 (2017), Cell Reports, Cell Reports, Elsevier Inc, 2017, 19 (4), pp.746-759. ⟨10.1016/j.celrep.2017.04.004⟩, Cell Reports, Elsevier Inc, 2017, 19 (4), pp.746-759. 〈http://www.sciencedirect.com/science/article/pii/S2211124717304631〉. 〈10.1016/j.celrep.2017.04.004〉
- Publication Year :
- 2017
- Publisher :
- Elsevier, 2017.
-
Abstract
- International audience; Sirtuin-1 deacetylates proteins and has emerged as a critical regulator of different cellular processes, particularly inflammation. Basal SIRT1 activity was previously found to limit Th9 and enhance Th17 differentiation in mice, but the effect of pharmacological SIRT1 activation on T cell differentiation and antitumor responses remains unclear. Here, we find that SIRT1 pharmacological agonists selectively impede mouse and human Th17 cell differentiation. SIRT1 activation induces STAT3 deacetylation, thus reducing its ability to translocate into the nucleus, bind to Rorc promoter, and induce its transcription. SIRT1 agonists reduce tumor growth in mice by blocking Th17 cell differentiation. In cancer patients, the SIRT1 agonist metformin reduced the frequency of Th17 cells and STAT3 acetylation levels. Altogether, these data underscore that SIRT1 activation impedes Th17 cell differentiation and thereby limits tumor growth and suggest that SIRT1 activators may directly target IL-17A functions.
- Subjects :
- CD4-Positive T-Lymphocytes
0301 basic medicine
endocrine system diseases
Cellular differentiation
Melanoma, Experimental
Regulator
environment and public health
[ SDV.CAN ] Life Sciences [q-bio]/Cancer
STAT3
Mice
Sirtuin 1
RAR-related orphan receptor gamma
lcsh:QH301-705.5
Mice, Inbred BALB C
biology
Acetylation
Cell Differentiation
Nuclear Receptor Subfamily 1, Group F, Member 3
Metformin
Cell biology
Th17
RORγt
medicine.symptom
biological phenomena, cell phenomena, and immunity
hormones, hormone substitutes, and hormone antagonists
STAT3 Transcription Factor
Agonist
medicine.drug_class
Transplantation, Heterologous
Carbazoles
Mice, Nude
Inflammation
[SDV.CAN]Life Sciences [q-bio]/Cancer
Heterocyclic Compounds, 4 or More Rings
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
SIRT1
Cell Line, Tumor
medicine
Animals
Humans
cancer
Molecular biology
Mice, Inbred C57BL
enzymes and coenzymes (carbohydrates)
030104 developmental biology
lcsh:Biology (General)
biology.protein
Th17 Cells
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 19
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....b348a4010ac9348ac9ee3ef93b38d58e