STATs in cancer inflammation and immunity: a leading role for STAT3

Yu, Hua; Pardoll, Drew; Jove, Richard

doi:10.1038/nrc2734

Cited by 4,383Cytokine Signaling Pathways and InteractionsImmune cells in cancerNF-κB Signaling Pathways

STATs in cancer inflammation and immunity: a leading role for STAT3

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Yu, Hua, Pardoll, Drew, Jove, Richard·2009·Nature reviews. Cancer

DOI 10.1038/nrc2734PMC PMC4856025

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Abstract

Commensurate with their roles in regulating cytokine-dependent inflammation and immunity, signal transducer and activator of transcription (STAT) proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer. Persistently activated STAT3 and, to some extent, STAT5 increase tumour cell proliferation, survival and invasion while suppressing anti-tumour immunity. The persistent activation of STAT3 also mediates tumour-promoting inflammation. STAT3 has this dual role in tumour inflammation and immunity by promoting pro-oncogenic inflammatory pathways, including nuclear factor-kappaB (NF-kappaB) and interleukin-6 (IL-6)-GP130-Janus kinase (JAK) pathways, and by opposing STAT1- and NF-kappaB-mediated T helper 1 anti-tumour immune responses. Consequently, STAT3 is a promising target to redirect inflammation for cancer therapy.

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IL-6 is a key factor in inflammation, autoimmunity and cancer, with its effect mainly exerted through the IL-6-STAT3 pathway.
“IL-6 is also a key factor in inflammation, autoimmunity and cancer, with its effect mainly exerted through the IL-6–signal transducer and activator of transcription 3 (STAT3) pathway (18–26, 61–65).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [19]
The ‘STAT proteins in immune modulation’ section describes IL-6 signalling through GP130–JAK to activate STAT3, and ‘STAT3 induces cancer inflammation’ describes IL-6-driven STAT3 activation in myeloma. The paper also calls STAT3 the major IL-6R-dependent transcription factor in T cells (‘STATs in anti-cancer or pro-cancer inflammation’). These passages support the inflammation-and-cancer link, but do not establish that IL-6 acts mainly through STAT3 across all the claimed contexts or directly characterize IL-6 as a key factor in autoimmunity; autoimmunity appears in reference titles. (LLM, conf=0.83)
Experimental — accuracy not yet measured
The IL-6-STAT3 pathway is now considered a major target for the treatment of inflammatory diseases.
“The IL-6–STAT3 pathway is now considered a major target for the treatment of inflammatory diseases (15, 19, 21, 24–26, 76).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [19]
In “Targeting STAT3 for cancer therapy” (page not supplied), the paper calls JAK kinases in IL-6–STAT3 signalling crucial targets for inflammation-induced cancer and cancer-associated inflammation. That supports targeting the pathway in a cancer-related setting, but not the broader claim that it is a major treatment target for inflammatory diseases generally. (LLM, conf=0.86)
Experimental — accuracy not yet measured
The crosstalk between STAT3 and NF-κB is an active field of research with studies showing contradictory outcomes of concomitant activation of the two TFs.
“The crosstalk between STAT3 and NF-κB is an active field of research with studies showing contradictory outcomes of concomitant activation of the two TFs.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [16]
Some studies suggest cooperation between STAT3 and NF-κB, while others show antagonism.
“Some suggest cooperation between them, while others show antagonism2, 16–21.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [16]
STAT3 is a key transcriptional mediator of cellular processes.
“STAT3, a member of the STATs family, is a key transcriptional mediator of cellular processes [43, 44].”
From Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation (2025) · cites this paper as [44]

These multiple signal transduction pathways intimately regulate cell survival, proliferation, inflammation, immunity, angiogenesis, and tumor development and progression through the expression of several genes.
“These multiple signal transduction pathways intimately regulate cell survival, proliferation, inflammation, immunity, angiogenesis, and tumor development and progression through the expression of several genes (1, 19, 21, 26, 31).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [19]
NF-κB and STAT3 play crucial roles in cancer development and progression.
“Furthermore, NF-κB and STAT3 play crucial roles in cancer development and progression (19, 25, 67, 279).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [19]
Other inhibitors against the IL-6-STAT3 signaling pathway are under development.
“Other inhibitors against the IL-6–STAT3 signaling pathway are under development (19, 21, 24–26, 76, 374).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [19]
Inhibition of aberrant STAT3 activation is a compelling target for HNSCC and CRC.
“the inhibition of aberrant STAT3 activation emerges as a compelling HNSCC and CRC target (8, 14, 15).”
From Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer (2022) · cites this paper as [15]
The events bringing about the hepatic immune response during inflammation remain elusive.
“Several models have been suggested2, 16 but the events bringing about the hepatic immune response during inflammation remain elusive.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [16]
The section “STAT3–NF-κB in cancer inflammation” says that a mechanism of immune-gene regulation in tumours remains unresolved, but it does not address what brings about the hepatic immune response during inflammation. A search for hepatic immune-response mechanisms found no passage in our copy that makes the attributed point. (LLM, conf=0.74)
Experimental — accuracy not yet measured
Activation of STAT signaling via cytokines such as IL-6 enhances cancer cell proliferation, survival, and invasion while suppressing host anti-tumor immunity.
“Activation of signal transducer and activator of transcription protein (STAT) signaling, via cytokines such as IL-6, is known to enhance cancer cell proliferation, survival, and invasion while also suppressing host anti-tumor immunity (71).”
From Diabetes and Cancer (2010) · cites this paper as [71]

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Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours
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Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target
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The Interleukin-10 Signal Transduction Pathway and Regulation of Gene Expression in Mononuclear Phagocytes
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Activation of Stat3 in Human Melanoma Promotes Brain Metastasis
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Stat3 regulates genes common to both wound healing and cancer
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STAT3 deletion during hematopoiesis causes Crohn’s disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity
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In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses
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A Critical Role for Stat3 Signaling in Immune Tolerance
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A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms
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Spinning molecular immunology into successful immunotherapy
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Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis
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STAT3 and STAT1 mediate IL-11–dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice
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Regulation of Dendritic Cell Differentiation and Antitumor Immune Response in Cancer by Pharmacologic-Selective Inhibition of the Janus-Activated Kinase 2/Signal Transducers and Activators of Transcription 3 Pathway
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STAT family of transcription factors in cytokine-mediated biological responses
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Role of STAT2 in the alpha interferon signaling pathway
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Indirubin derivatives inhibit Stat3 signaling and induce apoptosis in human cancer cells
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Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein
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The Role of STATs in Apoptosis
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Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells
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Novel peptidomimetic inhibitors of signal transducer and activator of transcription 3 dimerization and biological activity
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STAT3 tyrosine phosphorylation is critical for interleukin 1 beta and interleukin-6 production in response to lipopolysaccharide and live bacteria
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Constitutively activated Stat3 protects fibroblasts from serum withdrawal and UV-induced apoptosis and antagonizes the proapoptotic effects of activated Stat1
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Selectivity and therapeutic inhibition of kinases: to be or not to be?
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STAT signaling in the pathogenesis and treatment of leukemias
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Therapeutic targeting of Janus kinases
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Comparison of gene expression in HCT116 treatment derivatives generated by two different 5-fluorouracil exposure protocols.
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Activation of Signal Transducers and Activators of Transcription 3 and Focal Adhesion Kinase by Stromal Cell-Derived Factor 1 Is Required for Migration of Human Mesenchymal Stem Cells in Response to Tumor Cell-Conditioned Medium
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Knockdown of STAT3 Expression by RNA Interference Inhibits the Induction of Breast Tumors in Immunocompetent Mice
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β1 Integrin Adhesion Enhances IL-6–Mediated STAT3 Signaling in Myeloma Cells: Implications for Microenvironment Influence on Tumor Survival and Proliferation
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Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity
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Deletion of the SOCS3 Gene in Liver Parenchymal Cells Promotes Hepatitis–Induced Hepatocarcinogenesis
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Receptor‐mediated tobacco toxicity: cooperation of the Ras/Raf‐1/MEK1/ERK and JAK‐2/STAT‐3 pathways downstream of a7 nicotinic receptor in oral keratinocytes
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Interleukin-6 in the bone marrow microenvironment promotes the growth and survival of neuroblastoma cells
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The Serine Protease Plasmin Triggers Expression of MCP-1 and CD40 in Human Primary Monocytes via Activation of p38 MAPK and Janus Kinase (JAK)/STAT Signaling Pathways
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VEGF differentially activates STAT3 in microvascular endothelial cells
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Helicobacter pylori Cytotoxin-Associated Gene A Activates the Signal Transducer and Activator of Transcription 3 Pathway In vitro and In vivo
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A Novel Platinum Compound Inhibits Constitutive Stat3 Signaling and Induces Cell Cycle Arrest and Apoptosis of Malignant Cells
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Silibinin Inhibits Inflammatory and Angiogenic Attributes in Photocarcinogenesis in SKH-1 Hairless Mice
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Neuroendocrine modulation of signal transducer and activator of transcription-3 in ovarian cancer
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Activation of the Signal Transducers and Activators of the Transcription 3 Pathway in Alveolar Epithelial Cells Induces Inflammation and Adenocarcinomas in Mouse Lung
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Serine phosphorylation of STAT3 is essential for Mcl-1 expression and macrophage survival
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STAT3 Activation Regulates Growth, Inflammation, and Vascularization in a Mouse Model of Gastric Tumorigenesis
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STAT5A is epigenetically silenced by the tyrosine kinase NPM1-ALK and acts as a tumor suppressor by reciprocally inhibiting NPM1-ALK expression
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Inhibition of Bcr–Abl kinase activity by PD180970 blocks constitutive activation of Stat5 and growth of CML cells
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A Novel Inhibitor of Signal Transducers And Activators Of Transcription 3 Activation Is Efficacious Against Established Central Nervous System Melanoma and Inhibits Regulatory T Cells
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Toll-like receptor 9 activation of signal transducer and activator of transcription 3 constrains its agonist-based immunotherapy
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Autocrine Regulation of IL-21 Production in Human T Lymphocytes
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Toll-like receptors: lessons to learn from normal and malignant human B cells
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Thrombin Regulates Vascular Smooth Muscle Cell Growth and Heat Shock Proteins via the JAK-STAT Pathway
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IL-5 and Granulocyte-Macrophage Colony-Stimulating Factor Activate STAT3 and STAT5 and Promote Pim-1 and Cyclin D3 Protein Expression in Human Eosinophils
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Stat3 in Resident Macrophages as a Repressor Protein of Inflammatory Response
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Selective Expansion of Foxp3-Positive Regulatory T Cells and Immunosuppression by Suppressors of Cytokine Signaling 3-Deficient Dendritic Cells
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Cyclooxygenase-2-Dependent Activation of Signal Transducer and Activator of Transcription 3 by Interleukin-6 in Non–Small Cell Lung Cancer
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Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3α
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Defects along the TH17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome
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Effects of the JAK2 Inhibitor, AZ960, on Pim/BAD/BCL-xL Survival Signaling in the Human JAK2 V617F Cell Line SET-2
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Signal Transducer and Activator of Transcription 3 Is a Key Regulator of Keratinocyte Survival and Proliferation following UV Irradiation
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PTEN is a negative regulator of STAT3 activation in human papillomavirus-infected cells
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Distinct Roles of Different NF-κB Subunits in Regulating Inflammatory and T Cell Stimulatory Gene Expression in Dendritic Cells
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Sorafenib inhibits signal transducer and activator of transcription 3 signaling associated with growth arrest and apoptosis of medulloblastomas
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The Role of Interleukin 13 in Classical Hodgkin Lymphoma
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Deactivation of Akt and STAT3 signaling promotes apoptosis, inhibits proliferation, and enhances the sensitivity of hepatocellular carcinoma cells to an anticancer agent, Atiprimod
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“Many tumour viruses are also known to activate STAT3 by various distinct mechanisms, including hepatitis B viru”
Serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels in colorectal adenoma and cancer patients
Groblewska, M., Mroczko, B., Wereszczyńska-Siemiątkowska, U., Kędra, B., Łukaszewicz‐Zając, M., Baniukiewicz, A., & Szmitkowski, M. (2008) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2008.278 · Cited by 88 · see citing works
Protein Kinase Cε, which Sensitizes Skin to Sun's UV Radiation–Induced Cutaneous Damage and Development of Squamous Cell Carcinomas, Associates with Stat3
Aziz, M. H., Manoharan, H. T., & Verma, A. K. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3350 · Cited by 76 · see citing works
Stat3 enhances vimentin gene expression by binding to the antisilencer element and interacting with the repressor protein, ZBP-89
Wu, Y., Diab, I. H., Zhang, X., Izmailova, E. S., & Zehner, Z. E. (2004) · Oncogene · doi:10.1038/sj.onc.1207003 · Cited by 73 · see citing works
The role of constitutively active Stat6 in leukemia and lymphoma
Bruns, H. A., & Kaplan, M. H. (2005) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2005.08.005 · Cited by 73 · see citing works
c-Jun AND c-Fos COOPERATE WITH STAT3 IN IL-6-INDUCED TRANSACTIVATION OF THE IL-6 RESPONSE ELEMENT (IRE)
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Cytokine Overexpression and Constitutive NFκB in Cancer
Lu, T., & Stark, G. R. (2004) · Cell Cycle · doi:10.4161/cc.3.9.1130 · Cited by 60 · see citing works
Conformationally Constrained Peptidomimetic Inhibitors of Signal Transducer and Activator of Transcription 3: Evaluation and Molecular Modeling
Mandal, P. K., Limbrick, D., Coleman, D. R., Dyer, G. A., Ren, Z., Birtwistle, J. S., Xiong, C., Chen, X., Briggs, J. M., & McMurray, J. S. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm801491w · Cited by 58 · see citing works
New complexities in helper T cell fate determination and the implications for autoimmune diseases
Takatori, H., Kanno, Y., Chen, Z. J., & O’Shea, J. J. (2008) · Modern Rheumatology · doi:10.1007/s10165-008-0099-z · Cited by 56 · see citing works
Lack of toxicity of a STAT3 decoy oligonucleotide
Sen, M., Tosca, P. J., Zwayer, C., Ryan, M. J., Johnson, J. D., Knostman, K. A. B., Giclas, P. C., Peggins, J. O., Tomaszewski, J. E., McMurray, T. P., et al. (2009) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-008-0823-6 · Cited by 53 · see citing works
Src activation of Stat3 is an independent requirement from NF-κB activation for constitutive IL-8 expression in human pancreatic adenocarcinoma cells
Trevino, J. G., Gray, M. J., Nawrocki, S. T., Summy, J. M., Lesslie, D. P., Evans, D. B., Sawyer, T. K., Shakespeare, W. C., Watowich, S. S., Chiao, P. J., et al. (2006) · Angiogenesis · doi:10.1007/s10456-006-9038-9 · Cited by 52 · see citing works
Impaired development of human Th1 cells in patients with deficient expression of STAT4
Chang, H., Han, L., Goswami, R., et al. (2009) · Blood · doi:10.1182/blood-2008-09-179820 · Cited by 49 · see citing works
Epstein-Barr virus-derived EBNA2 regulates STAT3 activation
Muromoto, R., Ikeda, O., Okabe, K., Togi, S., Kamitani, S., Fujimuro, M., Harada, S., Oritani, K., & Matsuda, T. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.11.053 · Cited by 42 · see citing works
Stat6 Signaling Suppresses VLA-4 Expression by CD8+ T Cells and Limits Their Ability to Infiltrate Tumor Lesions In Vivo
Sasaki, K., Zhao, X., Pardee, A. D., Ueda, R., Fujita, M., Sehra, S., Kaplan, M. H., Kane, L., Okada, H., & Storkus, W. J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.1.104 · Cited by 31 · see citing works
New complexities in helper T cell fate determination and the implications for autoimmune diseases
Takatori, H., Kanno, Y., Chen, Z. J., et al. (2008) · Modern Rheumatology · doi:10.3109/s10165-008-0099-z · Cited by 26 · see citing works

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[127]Barton BE Karras JG Murphy TF Barton A Huang HF Signal transducer and activator of transcription 3 (STAT3) activation in prostate cancer: Direct STAT3 inhibition induces apoptosis in prostate cancer lines Mol. Cancer Ther 2004 3 11 20 14749471

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BackgroundInfluential
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STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor
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Stat3 controls lysosomal-mediated cell death in vivo
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Baricitinib restrains the immune dysregulation in patients with severe COVID-19
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MicroRNA-26a suppresses tumor growth and metastasis of human hepatocellular carcinoma by targeting interleukin-6-Stat3 pathway
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Hippo signaling interactions with Wnt/β-catenin and Notch signaling repress liver tumorigenesis
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IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation
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Breast cancer cells condition lymphatic endothelial cells within pre-metastatic niches to promote metastasis
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Cytokine Response Is Determined by Duration of Receptor and Signal Transducers and Activators of Transcription 3 (STAT3) Activation
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TNFα-senescence initiates a STAT-dependent positive feedback loop, leading to a sustained interferon signature, DNA damage, and cytokine secretion
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The expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia
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Dual inhibition of STAT1 and STAT3 activation downregulates expression of PD-L1 in human breast cancer cells
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A new link between diabetes and cancer: enhanced WNT/β-catenin signaling by high glucose
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DAMPs, ageing, and cancer: The ‘DAMP Hypothesis’
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Natural Withanolides in the Treatment of Chronic Diseases
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HER2 overexpression elicits a proinflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis
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STAT3 inhibition sensitizes colorectal cancer to chemoradiotherapy in vitro and in vivo
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STAT3, a master regulator of anti-tumor immune response
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Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis
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STAT3-YAP/TAZ signaling in endothelial cells promotes tumor angiogenesis
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Cell-state dynamics and therapeutic resistance in melanoma from the perspective of MITF and IFNγ pathways
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Nuclear PKM2 contributes to gefitinib resistance via upregulation of STAT3 activation in colorectal cancer
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Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells
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Assessing the future of solid tumor immunotherapy
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Mouse species-specific control of hepatocarcinogenesis and metabolism by FGF19/FGF15
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Chemotherapy-induced senescence, an adaptive mechanism driving resistance and tumor heterogeneity
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Filamentous recombinant human Tau activates primary astrocytes via an integrin receptor complex
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Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading
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“The JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway is one of the major mechanisms that regulates cytokine production (22, 23).”
Mesenchymal stem cells promote osteosarcoma cell survival and drug resistance through activation of STAT3
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RETRACTED ARTICLE: Transcriptional repression of SOCS3 mediated by IL-6/STAT3 signaling via DNMT1 promotes pancreatic cancer growth and metastasis
Huang, L., Hu, B., Ni, J., Wu, J., Jiang, W., Chen, C., Yang, L., Zeng, Y., Wan, R., Hu, G., et al. (2016) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-016-0301-7 · Cited by 86 · see citing works
Retracted
Targeting TGFβR2‐mutant tumors exposes vulnerabilities to stromal TGFβ blockade in pancreatic cancer
Huang, H., Zhang, Y., Gallegos, V., Sorrelle, N., Zaid, M. M., Toombs, J., Du, W., Wright, S., Hagopian, M., Wang, Z., et al. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201910515 · Cited by 87 · see citing works
“Tumor-infiltrating immune cells, including myeloid cells and lymphocytes, display a constitutive activation of STAT3 due to the stromal paracrine signals in the tumor niche (Yu et al, 2009).”
Background
Targeting myeloid derived suppressor cells reverts immune suppression and sensitizes BRAF-mutant papillary thyroid cancer to MAPK inhibitors
Zhang, P., Guan, H., Yuan, S., Cheng, H., Zheng, J., Zhang, Z., Liu, Y., Yu, Y., Meng, Z., Zheng, X., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29000-5 · Cited by 86 · see citing works
Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype
Ohanna, M., Cheli, Y., Bonet, C., Bonazzi, V. F., Allegra, M., Giuliano, S., Bille, K., Bahadoran, P., Giacchero, D., Lacour, J. P., et al. (2013) · Oncotarget · doi:10.18632/oncotarget.1143 · Cited by 78 · see citing works
Dietary iron enhances colonic inflammation and IL-6/IL-11-Stat3 signaling promoting colonic tumor development in mice
Chua, A. C. G., Klopcic, B. R. S., Ho, D. S., Fu, S. K., Forrest, C. H., Croft, K. D., Olynyk, J. K., Lawrance, I. C., & Trinder, D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078850 · Cited by 76 · see citing works
STAT3 in hepatocellular carcinoma: new perspectives
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Heparanase, cell signaling, and viral infections
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Aldose reductase inhibitors attenuate β-amyloid-induced TNF-α production in microlgia via ROS-PKC-mediated NF-κB and MAPK pathways
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The Mutant KRAS Gene Up-regulates BCL-XL Protein via STAT3 to Confer Apoptosis Resistance That Is Reversed by BIM Protein Induction and BCL-XL Antagonism
Zaanan, A., Okamoto, K., Kawakami, H., Khazaie, K., Huang, S., & Sinicrope, F. A. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.657833 · Cited by 59 · see citing works
DNA‐Binding Small Molecules as Inhibitors of Transcription Factors
Leung, C., Chan, D. S., Ma, V. P., & Ma, D. (2013) · Medicinal Research Reviews · doi:10.1002/med.21266 · Cited by 58 · see citing works
Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer
Jin, J., Wu, Y., Zhao, Z., Wu, Y., Zhou, Y.-D., Liu, S., Sun, Q., Yang, G., Lin, J., Nagle, D. G., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.160606 · Cited by 57 · see citing works
“Because the suppression of tumor cell apoptosis further contributes to reduced treatment response, the inhibition of aberrant STAT3 activation emerges as a compelling HNSCC and CRC target (8, 14, 15).”
Pharmacological features, health benefits and clinical implications of honokiol
Khatoon, F., Ali, S., Kumar, V., Elasbali, A. M., Alhassan, H. H., Alharethi, S. H., Islam, A., & Hassan, M. I. (2023) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2022.2120541 · Cited by 50 · see citing works
Antagonism of Interleukin-17A ameliorates experimental hepatic fibrosis by restoring the IL-10/STAT3-suppressed autophagy in hepatocytes
Zhang, X.-W., Mi, S., Li, Z., Zhou, J.-C., Xie, J., Hua, F., Li, K., Cui, B., Lv, X.-X., Yu, J.-J., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.14266 · Cited by 48 · see citing works
Regulation of Inflammatory Response by 3-Methyladenine Involves the Coordinative Actions on Akt and Glycogen Synthase Kinase 3β Rather than Autophagy
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Nuclear translocation of STAT3 and NF-κB are independent of each other but NF-κB supports expression and activation of STAT3
Martincuks, A., Andryka, K., Küster, A., Schmitz-Van de Leur, H., Komorowski, M., & Müller-Newen, G. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.01.006 · Cited by 45 · see citing works
Role of natural products in breast cancer related symptomology: Targeting chronic inflammation
Andrijauskaite, K., & Wargovich, M. J. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.08.011 · Cited by 38 · see citing works
STAT3 acts through pre-existing nucleosome-depleted regions bound by FOS during an epigenetic switch linking inflammation to cancer
Fleming, J. D., Giresi, P. G., Lindahl-Allen, M., Krall, E. B., Lieb, J. D., & Struhl, K. (2015) · Epigenetics & Chromatin · doi:10.1186/1756-8935-8-7 · Cited by 39 · see citing works
Genomic and computational approaches to dissect the mechanisms of STAT3’s universal and cell type-specific functions
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Sunitinib inhibits PD-L1 expression in osteosarcoma by targeting STAT3 and remodels the immune system in tumor-bearing mice
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Single cell profiling of phospho-protein levels in chronic lymphocytic leukemia
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Lack of gp130 expression in hepatocytes attenuates tumor progression in the DEN model
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STAT3 expression is associated with poor survival in non-elderly adult patients with newly diagnosed multiple myeloma
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Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation
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“STAT3, a member of the STATs family, is a key transcriptional mediator of cellular processes [43, 44].”
Inhibit versus Destroy: Are PROTAC Degraders the Solution to Targeting STAT3?
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Authors: Yu, H., Pardoll, D., & Jove, R.
Affiliations: City Of Hope National Medical Center (US)
Johns Hopkins University (US)
ORCID: Yu, Hua
Pardoll, Drew
Venue: Nature reviews. Cancer
Publisher: Springer Science and Business Media LLC
Published: 2009-11
Volume: 9
Issue: 11
Pages: 798-809
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc2734
PMC: PMC4856025
OpenAlex: W2044227662
Cited by: 4,383
References: 158
Citations by year: 2026: 233 · 2025: 234 · 2024: 286 · 2023: 264 · 2022: 288 · 2021: 363 · 2020: 276 · 2019: 259 · 2018: 268 · 2017: 283 · 2016: 283 · 2015: 248 · 2014: 295 · 2013: 268 · 2012: 205
FWCI: 15.58
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (P30CA021765, P30CA006973)
Topics: Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: STAT3, STAT5, STAT1, tumor microenvironment, antitumor immunity, NF-κB, interleukin-6, JAK signaling, Th1 cells, cancer therapy targets
MeSH terms: Animals, Humans, Immunity, Neoplasms, Signal Transduction, STAT Transcription Factors, STAT3 Transcription Factor, STAT5 Transcription Factor

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STATs in cancer inflammation and immunity: a leading role for STAT3

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