scholarly journals Increased B7-H4 expression during esophageal squamous cell carcinogenesis is associated with IL-6/STAT3 signaling pathway activation in mice

2017 ◽  
Vol 13 (4) ◽  
pp. 2207-2215 ◽  
Author(s):  
Xinran Chen ◽  
Wei Wang ◽  
Hongwei Man ◽  
Pengfei Li ◽  
Baoen Shan
Keyword(s):  
Signaling Pathway ◽  
Squamous Cell ◽  
Stat3 Signaling ◽  
Pathway Activation ◽  
Stat3 Signaling Pathway

scholarly journals Brusatol, a Nrf2 Inhibitor Targets STAT3 Signaling Cascade in Head and Neck Squamous Cell Carcinoma

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 550 ◽  
Author(s):  
Jong Hyun Lee ◽  
Shobith Rangappa ◽  
Chakrabhavi Dhananjaya Mohan ◽  
Basappa ◽  
Gautam Sethi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Transcription Factor ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Parp Cleavage ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

STAT3 is a latent transcription factor that plays a vital role in the transmission of extracellular signal from receptors to the nucleus. It has been regarded as a master transcription factor due to its role in the regulation of a broad spectrum of genes, which can contribute to oncogenesis. Persistent activation of STAT3 and deregulation of its signaling has been observed in various human cancers including head and neck squamous cell carcinoma (HNSCC). In the present work, we identified brusatol (BT) as a potential blocker of STAT3 signaling pathway in diverse HNSCC cells. The data from the cell-based experiments suggested that BT-induced cytotoxicity and abrogated the activation of STAT3 and that of upstream kinases such as JAK1, JAK2, and Src. It reduced the levels of nuclear STAT3 and its DNA binding ability. BT treatment increased annexin-V-positive cells, promoted procaspase-3 and PARP cleavage, and downregulated the mRNA and protein expression of diverse proteins (Bcl-2, Bcl-xl, survivin) in HNSCC cells. Taken together, brusatol can function as a promising inhibitor targeting STAT3 signaling pathway in HNSCC.

NME4 modulates PD-L1 expression via the STAT3 signaling pathway in squamous cell carcinoma

2020 ◽  
Vol 526 (1) ◽  
pp. 29-34
Author(s):  
Shutao Zheng ◽  
Qing Liu ◽  
Tao Liu ◽  
Lifei Yang ◽  
Qiqi Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals Metformin Downregulates PD-L1 Expression in Esophageal Squamous Cell Catrcinoma by Inhibiting IL-6 Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Yao Lu ◽  
Dao Xin ◽  
Lulu Guan ◽  
Mengli Xu ◽  
Yalan Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Esophageal Cancer ◽  
T Cell ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Antitumor Immune Response ◽  
Cancer Data ◽  
Stat3 Signaling ◽  
Coculture System ◽  
Stat3 Signaling Pathway

PurposeTo characterize the mechanism by which metformin inhibits PD-L1 expression in esophageal squamous cell carcinoma (ESCC) and to evaluate the effect of metformin on the antitumor immune response.MethodsThe Cancer Genome Atlas (TCGA) database was used to analyze the correlations between IL-6 and prognosis and between IL-6 and PD-L1 gene expression in esophageal cancer. Reverse transcription-quantitative polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence were used to study the mechanism by which metformin affects PD-L1 expression. Additionally, T cell function was assessed in a coculture system containing ESCC cells and peripheral blood mononuclear cells (PBMCs) treated with metformin or IL-6. In an in vivo assay, we used a model established with NPIdKO™ mice, which have a reconstituted immune system generated by transplanting PBMCs through intravenous injection, to evaluate the effect of metformin on tumors.ResultsThe TCGA esophageal cancer data showed that IL-6 expression was positively correlated with PD-L1 expression and that patients with high IL-6 expression had a significantly lower overall survival rate than patients with low IL-6 expression. PD-L1 expression in ESCC cell lines was significantly inhibited by metformin via the IL-6/JAK2/STAT3 signaling pathway but was not correlated with the canonical AMPK pathway. In the coculture system, the metformin pretreatment group showed higher T cell activation and better T cell killing function than the control group. Animal experiments confirmed that metformin downregulated PD-L1 expression and that combination treatment with metformin and PD-1 inhibitors synergistically enhanced the antitumor response.ConclusionsMetformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response.

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