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

By Hua Yu, D. Pardoll, R. Jove. Nature Reviews. Cancer, 2009

4,361 citations recorded by the source corpus.

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-κB (NF-κB) and interleukin-6 (IL-6)–GP130–Janus kinase (JAK) pathways, and by opposing STAT1- and NF-κB-mediated T helper 1 anti-tumour immune responses. Consequently, STAT3 is a promising target to redirect inflammation for cancer therapy.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/f9e6a2bfbf3a3a9484e08acdb4fdd0f2755213a2

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Citations in the corpus

STAT3 activation of miR-21 and miR-181b-1, via PTEN and CYLD, are part of the epigenetic switch linking inflammation to cancer (2010, result): “This observation is consistent with the conventional view that STAT3 is a downstream effector of IL-6 (Frank, 2007; Yu et al., 2007, 2009), but not part of the central regulatory circuit that mediates the epigenetic switch.”
Inflammation and Cancer: Triggers, Mechanisms and Consequences (2019, background): “Signals activating STAT3 protect epithelial cells from CD8 T cytotoxic cell attack (Yu et al., 2009; Ziegler et al., 2018) and signaling by IFNκ, albeit a typically anti-tumorigenic cytokine, upregulates expression of T cell exhaustion inducing molecule programmed death (PD)-L1 on transformed epithe”
Regulation of PD-L1: a novel role of pro-survival signalling in cancer. (2016, background): “Gowrishankar K, Gunatilake D, Gallagher SJ et al. Inducible but not constitutive expression of PD-L1 in human melanoma cells is dependent on activation of NF-κB.”
IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis. (2014, background): “Nonetheless, tissue and cell-type–specific differences in the activation of the IL-6R/STAT3/ miR-34a loop may exist, since STAT3 activation can be achieved via multiple other signaling pathways, such as receptor-tyrosine kinases, deregulated in cancer (41).”
Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. (2011, background): “Stat3 regulates its own endogenous inhibitor, Socs3, to form a negative feedback loop (Yu et al., 2009).”
FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling. (2016, background): “The role of STAT3 in cancer has been largely focused on tumor cells and myeloid cells (18,32), however, we showed robust STAT3 activation in CAFs, which is consistent with several studies (29,33), and identify FAP as a persistent activator of fibroblastic STAT3, which in turn mediates inflammatory p”
Targeting interleukin-6 in inflammatory autoimmune diseases and cancers. (2014, background): “STAT3 is an important regulator for a number of anti-apoptotic genes, and its activity is associated with tumor growth, survival, angiogenesis, andmetastatic processes (Yu et al., 2009).”
IL-6 in inflammation, autoimmunity and cancer (2020, background): “Other inhibitors against the IL-6–STAT3 signaling pathway are under development (19, 21, 24–26, 76, 374).”
Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors. (2014, background): “mediators, such as IL-6, IL-1β, macrophage colony-stimulating factor, prostaglandins and cyclooxygenase-2 (COX-2) are crucial for inducing and maintaining a cancer-promoting inflammatory environment, and STAT3 is crucial for regulating their expression [13].”