Naoya Inamura1, Taichi Kimura2, Lei Wang3, Hiroko Yanagi1, Masumi Tsuda4, Mishie Tanino4, Hiroshi Nishihara3, Satoshi Fukuda1, Shinya Tanaka5. 1. Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan. 2. Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan. Electronic address: ktaichi@syd.odn.ne.jp. 3. Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan. 4. Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan. 5. Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan; Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan.
Abstract
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.
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.
Authors: Yang Zheng; Zhao Wang; Xu Ding; Wei Zhang; Gang Li; Laikui Liu; Heming Wu; Wenyi Gu; Yunong Wu; Xiaomeng Song Journal: Cancer Cell Int Date: 2018-01-08 Impact factor: 5.722
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