The IL6 STAT3 signaling pathway is a cytokine-driven signaling cascade that plays a central role in inflammation, immune regulation, cell survival, and proliferation. It is activated when interleukin-6 (IL-6) binds to its receptor complex, leading to JAK-mediated phosphorylation of STAT3 and transcriptional regulation of downstream target genes.
This pathway is essential for normal immune responses and tissue repair. However, persistent activation of IL6 STAT3 signaling is strongly associated with chronic inflammatory diseases, cancer progression, immune evasion, and resistance to therapy.
IL6 STAT3 pathway activity can be efficiently assessed by measuring gene expression of pathway regulators and STAT3-dependent biomarkers.
Highly suitable for biomarker discovery and gene expression profiling
Core components of the IL6 STAT3 signaling pathway
IL-6
A pleiotropic cytokine involved in immune activation, acute-phase responses, and tissue regeneration. Dysregulated IL-6 production sustains chronic inflammation and tumor-promoting environments.
JAK kinases
JAK1, JAK2, and TYK2 phosphorylate STAT3 following IL-6 receptor engagement.
STAT3
A transcription factor that controls genes involved in survival, proliferation, angiogenesis, immune suppression, and metastasis.
Negative regulators
SOCS proteins and phosphatases limit signal duration and intensity.
Mechanism of IL6 STAT3 signaling
IL-6 binds to IL-6R / gp130 receptor complex
JAK kinases are activated
STAT3 is phosphorylated and dimerizes
STAT3 translocates to the nucleus
Transcription of inflammation- and cancer-related genes
IL6 STAT3 signaling interacts with PI3K/AKT, NF-κB, MAPK, and mTOR pathways, amplifying disease-relevant responses.
Biological functions
The IL6 STAT3 pathway regulates:
Inflammatory cytokine production
Immune cell activation and balance
Cell survival and apoptosis resistance
Angiogenesis and tissue remodeling
Tumor growth and immune escape
IL6 STAT3 signaling pathway in disease
Cancer
Persistent STAT3 activation promotes:
Tumor cell proliferation
Angiogenesis (e.g. VEGF expression)
Immune suppression
Resistance to targeted therapies
Autoimmune and inflammatory diseases
Chronic IL6 STAT3 signaling contributes to:
Rheumatoid arthritis
Lupus
Psoriasis
Inflammatory bowel disease
Metabolic and cardiovascular diseases
STAT3-driven inflammation is linked to insulin resistance, obesity, and vascular dysfunction.
Therapeutic targeting and biomarker relevance
The IL6 STAT3 pathway is a major therapeutic target:
Anti-IL-6 and anti-IL-6R antibodies
JAK inhibitors
STAT3 pathway inhibitors
Gene expression–based biomarker analysis is essential for patient stratification and treatment monitoring.
Why study the IL6 STAT3 signaling pathway with AnyGenes?
At AnyGenes®, we provide high-performance qPCR arrays and customizable SignArrays® designed for IL6 STAT3 pathway analysis.
Our solutions enable researchers to:
Quantify IL6 STAT3 gene expression signatures
Analyze downstream STAT3 transcriptional targets
Study pathway cross-talk with inflammation and cancer pathways
By measuring expression of pathway regulators and downstream genes using targeted qPCR pathway arrays.
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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.
Galoczova M, et al. STAT3, stem cells, cancer stem cells and p63. Cell Mol Biol Lett. (2018)22;23:12.
Johnson DE, et al. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. (2018);15(4):234-248.
Yan Lin et al. Progress in Understanding the IL-6/STAT3 Pathway in Colorectal Cancer. Onco Targets Ther. (2020)21;13:13023-13032.
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.
Liu Y, et al. STAT3 and its targeting inhibitors in osteosarcoma. Cell Prolif. (2021);54(2):e12974.
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.
Mohrherr J, et al. STAT3: Versatile Functions in Non-Small Cell Lung Cancer. Cancers (Basel). (2020)29;12(5):1107.
IL6 STAT3 signaling pathway biomarker list
You can check the biomarker list included in this pathway, see below: