Targeting of EZH2 inhibits epithelial‑mesenchymal transition in head and neck squamous cell carcinoma via regulating the STAT3/VEGFR2 axis

Zhao,Minghui; Hu,Xiaomeng; Xu,Yini; Wu,Chuanqiang; Chen,Jinliang; Ren,Yu; Kong,Lingping; Sun,Shanshan; Zhang,Lun; Jin,Rui; Zhou,Xuan

doi:10.3892/ijo.2019.4880

Targeting of EZH2 inhibits epithelial‑mesenchymal transition in head and neck squamous cell carcinoma via regulating the STAT3/VEGFR2 axis

Authors:
- Minghui Zhao
- Xiaomeng Hu
- Yini Xu
- Chuanqiang Wu
- Jinliang Chen
- Yu Ren
- Lingping Kong
- Shanshan Sun
- Lun Zhang
- Rui Jin
- Xuan Zhou
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Affiliations: Department of Maxillofacial and Otorhinolaryngology Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin 300060, P.R. China, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, P.R. China
Published online on: September 18, 2019 https://doi.org/10.3892/ijo.2019.4880
Pages: 1165-1175

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Abstract

Tumor metastasis regulated by epithelial‑mesenchymal transition (EMT) plays a significant role in the development of human cancers, whereas the molecular mechanisms of this process in head and neck squamous cell carcinoma (HNSCC) remain elusive. In this study, we found that inhibition of enhancer of zeste homolog 2 (EZH2) resulted in suppressed EMT in HNSCC in vitro and in vivo. 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. EZH2 inhibition downregulated the expression of key molecules of the STAT3/VEGFR2 axis and EMT‑related markers, while the expression of E‑cadherin was upregulated in HNSCC cells. Targeting the EZH2/STAT3/VEGFR2 axis significantly reduced motility of HNSCC cells. Furthermore, EZH2 knockdown reduced the growth of xenograft HNSCC tumors via inhibiting the EZH2/STAT3/VEGFR2 axis. In conclusion, we proposed that EZH2 regulates EMT and tumor invasion and metastasis in HNSCC by governing the STAT3/VEGFR2 axis. These findings provide a rationale for developing novel strategies to treat invasive and metastatic HNSCC via targeting the EZH2/STAT3/VEGFR2 pathway.

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