scholarly journals Targeting STAT3 in Cancer Immunotherapy

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Sailan Zou ◽  
Qiyu Tong ◽  
Bowen Liu ◽  
Wei Huang ◽  
Yan Tian ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Therapeutic Strategy ◽  
Current Status ◽  
Therapeutic Approaches ◽  
Oncogenic Signaling ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Oncogenic Signaling Pathways ◽  
Transcription 3 ◽  
Cancerous Cells

Abstract As a point of convergence for numerous oncogenic signaling pathways, signal transducer and activator of transcription 3 (STAT3) is central in regulating the anti-tumor immune response. STAT3 is broadly hyperactivated both in cancer and non-cancerous cells within the tumor ecosystem and plays important roles in inhibiting the expression of crucial immune activation regulators and promoting the production of immunosuppressive factors. Therefore, targeting the STAT3 signaling pathway has emerged as a promising therapeutic strategy for numerous cancers. In this review, we outline the importance of STAT3 signaling pathway in tumorigenesis and its immune regulation, and highlight the current status for the development of STAT3-targeting therapeutic approaches. We also summarize and discuss recent advances in STAT3-based combination immunotherapy in detail. These endeavors provide new insights into the translational application of STAT3 in cancer and may contribute to the promotion of more effective treatments toward malignancies.

scholarly journals KDM3A histone demethylase functions as an essential factor for activation of JAK2−STAT3 signaling pathway

2018 ◽  
Vol 115 (46) ◽  
pp. 11766-11771 ◽  
Author(s):  
Hyunkyung Kim ◽  
Dongha Kim ◽  
Seon Ah Choi ◽  
Chang Rok Kim ◽  
Se Kyu Oh ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Therapeutic Strategy ◽  
Transcriptional Coactivator ◽  
Essential Factor ◽  
Stat3 Signaling ◽  
Lysine Specific Demethylase ◽  
Tyrosine Kinase 2 ◽  
Stat3 Signaling Pathway ◽  
Janus Tyrosine Kinase 2 ◽  
Transcription 3

Janus tyrosine kinase 2 (JAK2)−signal transducer and activator of transcription 3 (STAT3) signaling pathway is essential for modulating cellular development, differentiation, and homeostasis. Thus, dysregulation of JAK2−STAT3 signaling pathway is frequently associated with human malignancies. Here, we provide evidence that lysine-specific demethylase 3A (KDM3A) functions as an essential epigenetic enzyme for the activation of JAK2−STAT3 signaling pathway. KDM3A is tyrosine-phosphorylated by JAK2 in the nucleus and functions as a STAT3-dependent transcriptional coactivator. JAK2−KDM3A signaling cascade induced by IL-6 leads to alteration of histone H3K9 methylation as a predominant epigenetic event, thereby providing the functional and mechanistic link between activation of JAK2−STAT3 signaling pathway and its epigenetic control. Together, our findings demonstrate that inhibition of KDM3A phosphorylation could be a potent therapeutic strategy to control oncogenic effect of JAK2−STAT3 signaling pathway.

scholarly journals 3-Formylchromone Counteracts STAT3 Signaling Pathway by Elevating SHP-2 Expression in Hepatocellular Carcinoma

Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 29
Author(s):  
Chakrabhavi Dhananjaya Mohan ◽  
Min Hee Yang ◽  
Shobith Rangappa ◽  
Arunachalam Chinnathambi ◽  
Sulaiman Ali Alharbi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Tyrosine Kinases ◽  
Present Report ◽  
Migration And Invasion ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Substantial Toxicity ◽  
Transcription 3 ◽  
Constitutive Phosphorylation

Hepatocellular carcinoma (HCC) is one of the leading cancers that contribute to a large number of deaths throughout the globe. The signal transducer and activator of transcription 3 (STAT3) is a tumorigenic protein that is overactivated in several human malignancies including HCC. In the present report, the effect of 3-formylchromone (3FC) on the STAT3 signaling pathway in the HCC model was investigated. 3FC downregulated the constitutive phosphorylation of STAT3 and non-receptor tyrosine kinases such as JAK1 and JAK2. It also suppressed the transportation of STAT3 to the nucleus and reduced its DNA-binding ability. Pervanadate treatment overrode the 3FC-triggered STAT3 inhibition, and the profiling of cellular phosphatase expression revealed an increase in SHP-2 levels upon 3FC treatment. The siRNA-driven deletion of SHP-2 led to reinstate STAT3 activation. 3FC downmodulated the levels of various oncogenic proteins and decreased CXCL12-driven cell migration and invasion. Interestingly, 3FC did not exhibit any substantial toxicity, whereas it significantly regressed tumor growth in an orthotopic HCC mouse model and abrogated lung metastasis. Overall, 3FC can function as a potent agent that can display antitumor activity by targeting STAT3 signaling in HCC models.

scholarly journals Interplay between microRNAs and the STAT3 signaling pathway in human cancers

2013 ◽  
Vol 45 (24) ◽  
pp. 1206-1214 ◽  
Author(s):  
Qing Cao ◽  
Yun-Yun Li ◽  
Wen-Feng He ◽  
Zhong-Zu Zhang ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Messenger Rna ◽  
Cancer Therapeutics ◽  
Protein Coding ◽  
Reciprocal Regulation ◽  
Regulate Gene Expression ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Egfr Genes ◽  
Transcription 3

MicroRNAs (miRNAs, also miR) are a class of noncoding endogenous RNAs that regulate gene expression through binding to protein-coding messenger RNA (mRNA) molecules, predominantly within the 3′-untranslated region (3′-UTR). Signal transducer and activator of transcription 3 ( STAT3) is a transcription factor that regulates a battery of genes involved in regulating a variety of biological processes. There is a growing body of evidence demonstrating that miRNAs are closely associated with the STAT3 signaling pathway. In this review, we focus on interactions between miRNAs and the STAT3 signaling pathway, focusing on their reciprocal regulation and roles in cancer. For instance, several papers independently support the existence of regulatory feedback loops between miRNAs and the STAT3 pathway in different cancer contexts including IL-6-STAT3-miR-24/miR-629-HNF4α-miR-124 and IL-6R-STAT3-NF-κB-Lin-28-let-7a. Furthermore, several miRNA components are reported to be involved in STAT3-mediated tumorigenesis, for example miR-21, miR-155, and miR-181b. Through binding to STAT3-binding sites within the promoters of these oncomiRs, STAT3 activates their transcription and mediates tumorigenesis. Some miRNAs directly modulate STAT3 activity through targeting the STAT3 3′-UTR; other miRNAs target SOCS, PIAS3, and EGFR genes, which encode proteins that regulate the STAT3 signaling pathway. Given that miRNAs represent a newly discovered class of regulatory molecules, investigating their biological functions and contribution to pathologies caused by STAT3 dysregulation is essential to improve our understanding of tumorigenesis and to develop novel anticancer therapeutics. The more we can learn about miRNAs- STAT3 interactions, the better able we will be to manipulate them for developing cancer therapeutics.

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