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AnyGenes

Signaling Pathways title  IL6-STAT3

 IL6

Interleukin-6 (IL-6) is a pleiotropic cytokine with roles in immunity, tissue regeneration, and metabolism, but excessive synthesis of IL-6 and dysregulation of IL-6 receptor signaling is involved in disease pathology (1) such as acute inflammatory responses, autoimmune diseases, and tumor formation (2).

STAT3

Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor with many important functions in the biology of normal and transformed cells. Besides other functions, STAT3 is an important regulator of normal stem cells and cancer stem cells (3).

The IL-6/JAK/STAT3 pathway is aberrantly hyperactivated in many types of cancer. In the tumour microenvironment, IL-6/JAK/STAT3 signalling acts to drive the proliferation, survival, invasiveness, and metastasis of tumour cells, while strongly suppressing the antitumour immune response (4).

Signaling Pathways title  Signaling Pathways

The main function of the classical pathway is to induce anti-inflammatory effects during the acute-phase response (5).
IL6-STAT3_mechanisme

 
Signalling downstream of the IL-6 receptor (4)
.

Signaling Pathways title  IL6-STAT3 signaling pathway and diseases

IL6-STAT3 signaling pathway is involved in a wide spectrum of diseases :
  • Saphenous vein graft failure (SVGF) (6).
  • STAT3 is considered a proto-oncogene and it is implicated in the development of various cancers, including multiple myeloma, leukaemia and lymphomas (7).
  • Osteosarcoma (7).
  • Colitis (8).
  • Non-Small Cell Lung Cancer (NSCLC) (9). (2).
(1) Kang S, et al. Targeting Interleukin-6 Signaling in Clinic. Immunity. (2019) 16;50(4):1007-1023.
(2) Song Z, et al. Molecular cross-talk of IL-6 in tumors and new progress in combined therapy. Thorac Cancer. (2018);9(6):669-675.
(3) Galoczova M, et al. STAT3, stem cells, cancer stem cells and p63. Cell Mol Biol Lett. (2018)22;23:12.
(4) Johnson DE, et al. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. (2018);15(4):234-248.
(5) Yan Lin et al. Progress in Understanding the IL-6/STAT3 Pathway in Colorectal Cancer. Onco Targets Ther. (2020)21;13:13023-13032.
(6) Moshapa FT, et al. Therapeutic Targeting of the Proinflammatory IL-6-JAK/STAT Signalling Pathways Responsible for Vascular Restenosis in Type 2 Diabetes Mellitus. Cardiol Res Pract. (2019)2;2019:9846312.
(7) Liu Y, et al. STAT3 and its targeting inhibitors in osteosarcoma. Cell Prolif. (2021);54(2):e12974.
(8) Kasembeli MM, et al. Contribution of STAT3 to Inflammatory and Fibrotic Diseases and Prospects for its Targeting for Treatment. Int J Mol Sci. (2018)5;19(8):2299.
 (9) Mohrherr J, et al. STAT3: Versatile Functions in Non-Small Cell Lung Cancer. Cancers (Basel). (2020)29;12(5):1107.
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