Notch1 regulates invasion and metastasis of head and neck squamous cell carcinoma by inducing EMT through c-Myc

Naoya Inamura, Taichi Kimura, Lei Wang, Hiroko Yanagi, Masumi Tsuda, Mishie Tanino, Hiroshi Nishihara, Satoshi Fukuda, Shinya Tanaka

研究成果: Article査読

23 被引用数 (Scopus)

抄録

Objective As 50% of patients of head and neck squamous carcinoma (HNSCC) exhibit poor prognosis, the identification of new therapeutic targets is required. Recently, there have been several reports about the correlation between Notch1 and HNSCC, but the precise mechanism is still obscure. Therefore, in this study, we examined the involvement of Notch1 in HNSCC by using HNSCC cell lines and surgical specimens. Methods To investigate the role of Notch1 in HNSCC, we examined the effect of Notch inhibitor DAPT on cell growth, invasion, and tumorigenicity using five HNSCC cell lines in vitro and in vivo. We further examined that the correlation with Notch expression and clinical prognostic factors was evaluated by using 101 HNSCC surgical specimens. Results DAPT reduced the nuclear expression of Notch and c-Myc and repressed cell growth, EMT-dependent cell invasion in vitro, and tumorigenicity in vivo. An overexpression of Myc enhanced EMT with an increase of Snail and vimentin together with decreased levels of E-cadherin in HSC3 cells. Finally, we discovered that Notch expression was well correlated with MIB-1 index and lymph node metastases. Conclusion We discovered that Notch1 was strongly correlated with HNSCC growth, invasion, and metastases. Therefore, Notch1 might be a new therapeutic target and a predictive marker of proliferation and metastasis of HNSCC.

本文言語English
ページ(範囲)447-457
ページ数11
ジャーナルAuris Nasus Larynx
44
4
DOI
出版ステータスPublished - 2017 8月
外部発表はい

ASJC Scopus subject areas

  • 外科
  • 耳鼻咽喉科学

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