We reported that signal transducer and activator of transcription factor 3 (STAT3)/vascular endothelial growth factor receptor 2 (VEGFR2) axis served as the downstream signaling of EZH2 and mediated EMT in HNSCC.
Persistent activation of STAT3 and deregulation of its signaling has been observed in various human cancers including head and neck squamous cell carcinoma (HNSCC).
Taken together, these results indicate that C188-9 could be a promising therapeutic strategy for patients suffered from HNSCC by suppressing the STAT3 pathway.
STOML2 as a novel prognostic biomarker modulates cell proliferation, motility and chemo-sensitivity via IL6-Stat3 pathway in head and neck squamous cell carcinoma.
In summary, our discoveries illuminate how aberrant STAT3 activation confers an oncogenic function in HNSCC and therefore may provide a theoretical foundation for STAT3 as a therapeutic target in HNSCC.
Importantly, we found that active STAT3 in tumors directly correlated with response to cisplatin-based chemoradiotherapy in HNSCC patients (<i>p</i> = 0.006).
In this study, we show that HJC0152, a recently developed anticancer agent and a STAT3 signaling inhibitor, exhibits promising antitumor effects against HNSCC both <i>in vitro</i> and <i>in vivo</i> via inactivating STAT3 and downstream miR-21/β-catenin axis.
We further show that PTPRT promoter methylation is significantly associated with sensitivity to STAT3 inhibition in HNSCC cells, suggesting that PTPRT promoter methylation may serve as a predictive biomarker for responsiveness to STAT3 inhibitors in clinical development.
We found that HN3 and FaDu cells expressed strongly phosphorylated STAT3 on both tyrosine 705 and serine 727 residues as compared to other SCCHN cells.
Since STAT3 activation is involved in tumor progression and metastasis, we investigated the effect of GSNO in cell culture and mouse xenograft model of head and neck squamous cell carcinoma (HNSCC).
Since STAT3 and NF-κB are key transcription factors involved in tumor progression, chemoresistance, and metastasis of head and neck cancer, we investigated the effect of GSNO in cell culture and mouse xenograft models of head and neck squamous cell carcinoma (HNSCC).
We additionally found that PTPRD mRNA expression does not correlate with pSTAT3 expression, suggesting that alterations that manifest through altered mRNA expression, including hypermethylation and gene copy number alterations, do not significantly contribute to STAT3 overactivation in HNSCC.
Immunohistochemical analysis confirmed that HPV- HNSCC is characterized by co-activated STAT3 and NF-κB pathways and functional studies demonstrate that this phenotype can be effectively targeted with combined anti-NF-κB and anti-STAT therapies.
Signal transducer and activator of transcription 3 (STAT3) has shown to play a critical role in head and neck squamous cell carcinoma (HNSCC) and we have recently completed clinical trials of STAT3 decoy oligonucleotide in patients with recurrent or metastatic HNSCC.
The findings were further supported using chemical inhibitors of STAT3 activity (a downstream effecter of uPAR signaling pathway), showing that STAT3 suppression altered HNSCC cell line cisplatin sensitivity.