The Roles of post-translational Modifications and Coactivators of STAT6 Signaling in Tumor Growth and Progression

Huang, Hao; Zheng, Yizhou; Li, Linfu; Shi, Weimei; Zhang, Rui; Liu, Hai; Chen, Zhixi; Wu, Longhuo

doi:10.4155/fmc-2020-0224

Cited by 9 publications

(15 citation statements)

References 125 publications

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“…STAT6 plays a role in tumorigenesis, immunosuppression, proliferation, and metastasis of human cancers. The highly activated IL‐4/IL‐4Ra/STAT6 signaling in prostate cancer stem cell‐like cells validates the tumorigenic activity of STAT6 26 . However, the results of these studies contradict our findings.…”

Section: Discussioncontrasting

confidence: 76%

“…Sultan et al demonstrated that STAT5A induces E‐cadherin and promotes β‐catenin binding to the cell surface through E‐cadherin‐mediated linkage, thereby inhibiting human breast cancer cells 8 . In another study, increased expression of IL‐4/STAT6 signaling was associated with reduced tumor volume and weight, as well as the increased expression of apoptotic proteins 26 . However, the role of STAT5 in promoting tumor development has also been documented.…”

Section: Discussionmentioning

confidence: 99%

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Signal transducer and activator of transcription family is a prognostic marker associated with immune infiltration in endometrial cancer

Zhou

Dai

et al. 2022

Clinical Laboratory Analysis

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Background Signal transducer and activator of transcription (STAT) is a unique protein family that binds to DNA and plays a vital role in regulating major physiological cellular processes. Seven STAT genes have been identified in the human genome. Several studies suggest STAT family members to be involved in cancer development, progression, and metastasis. However, the predictive relationship between STAT family expression and immune cell infiltration in endometrial cancer remains unknown. Methods We explored STAT family expression and prognosis in endometrial cancer using various databases. The STRING, GeneMANIA, and DAVID databases, along with GO and KEGG analyses, were used to construct a protein interaction network of related genes. Finally, the TIMER database and ssGSEA immune infiltration algorithm were used to investigate the correlation of STAT family expression with the immune infiltration level in uterine corpus endometrial carcinoma (UCEC). Results Our study showed that different STAT family members are differentially expressed in UCEC. STAT1 and STAT2 expression increased at various stages of UCEC, and STAT5A, STAT5B, and STAT6 levels were decreased. STAT3 and STAT4 expression was not significantly different between UCEC and normal tissues. High STAT1 expression may be a prognostic disadvantage of UCEC, and high STAT6 expression may improve UCEC patient prognosis. The STAT family‐associated genes were significantly enriched in signal transduction, protein binding, DNA binding, and ATP binding upon GO analysis. Related genes in the KEGG analysis were mainly enriched in pathways in cancer, viral carcinogenesis, chemokine signaling pathway, JAK/STAT signaling pathway, and regulation of the actin cytoskeleton. In terms of immune infiltration, STAT1 and STAT2 were positively correlated with B, CD8+ T, CD4+ T, and dendritic cells, and neutrophils (p < 0.05). All STAT family members were positively correlated with neutrophils and dendritic cells (p < 0.05). STAT1 and STAT2 showed similar correlations with all immune cell types, whereas STAT1 and STAT6 showed opposite correlations. Conclusion These findings suggest that the STAT family is a prognostic marker, and the immune infiltration level, a therapeutic target, for endometrial cancer.

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Section: Discussioncontrasting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Signal transducer and activator of transcription family is a prognostic marker associated with immune infiltration in endometrial cancer

Zhou

Dai

et al. 2022

Clinical Laboratory Analysis

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“…The correlation between aberrant STAT6 activity/expression levels and the size of the PAs suggested that overactivation of STAT6 increased the risk of developing MACs as opposed to MICs. Previous studies have shown that STAT6 is associated with the tumorigenesis, immunosuppression, proliferation, metastasis and poor prognosis of human cancers [ 17 ]. For example, STAT6 activation promotes the malignant behavior of colon cancer, prostate cancer, breast cancer and mediastinal large B-cell lymphoma cells [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen Exerts Anticancer Effects on Pituitary Adenoma Progression via Inducing Cell Apoptosis and Inhibiting Cell Migration

Zhang

et al. 2022

IJMS

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Although pituitary adenomas are histologically benign, they are often accompanied by multiple complications, such as cardiovascular disease and metabolic dysfunction. In the present study, we repositioned the Food and Drug Administration -approved immune regulator tamoxifen to target STAT6 based on the genomics analysis of PAs. Tamoxifen inhibited the proliferation of GH3 and AtT-20 cells with respective IC50 values of 9.15 and 7.52 μM and increased their apoptotic rates in a dose-dependent manner. At the molecular level, tamoxifen downregulated phosphorylated PI3K, phosphorylated AKT and the anti-apoptotic protein Bcl-2 and increased the expression of pro-apoptotic proteins p53 and Bax in GH3 and AtT-20 cells. Furthermore, tamoxifen also inhibited the migration of both cell lines by reprogramming tumor-associated macrophages to the M1 phenotype through STAT6 inactivation and inhibition of the macrophage-specific immune checkpoint SHP1/SHP. Finally, administration of tamoxifen (20, 50, 100 mg·kg−1·d−1, for 21 days) inhibited the growth of pituitary adenomas xenografts in nude mice in a dose-dependent manner. Taken together, tamoxifen is likely to be a promising combination therapy for pituitary adenomas and should be investigated further.

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“…Available online at: https://www. accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=668818 28 Clinicaltrials.gov Available online at: https://clinicaltrials.gov/ct2/show/ NCT04322708 through the action of Janus family (JAKs) tyrosine kinases (Huang et al, 2020). It acts as a Th2-inducing transcriptional activator (Goenka and Kaplan, 2011) and is implicated in the immunity to helminths and in the pathophysiology of various allergic conditions (Karpathiou et al, 2021).…”

Section: Transcription Factors the Signal Transducer And Activator Of Transcription 6 Pathwaymentioning

confidence: 99%

“…IL-4 and IL-13, together with IL-3, IL-15, IL-33, IFNα and platelet-derived growth factor-PDGF, can activate STAT6 through the action of Janus family (JAKs) tyrosine kinases ( Huang et al, 2020 ). It acts as a Th2-inducing transcriptional activator ( Goenka and Kaplan, 2011 ) and is implicated in the immunity to helminths and in the pathophysiology of various allergic conditions ( Karpathiou et al, 2021 ).…”

Section: Focus On Type 2 Inflammation: the Protagonistsmentioning

confidence: 99%

Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets

et al. 2022

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Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients’ quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature.

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The Roles of post-translational Modifications and Coactivators of STAT6 Signaling in Tumor Growth and Progression

Cited by 9 publications

References 125 publications

Signal transducer and activator of transcription family is a prognostic marker associated with immune infiltration in endometrial cancer

Signal transducer and activator of transcription family is a prognostic marker associated with immune infiltration in endometrial cancer

Tamoxifen Exerts Anticancer Effects on Pituitary Adenoma Progression via Inducing Cell Apoptosis and Inhibiting Cell Migration

Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets

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