Expression and Oncogenic Properties of Membranous Notch1 in Oral Leukoplakia and Oral Squamous Cell Carcinoma

Overview

Journal Oncol Rep

Specialty Oncology

Date 2018 Apr 6

PMID 29620248

Citations 11

Authors

Xu Ding

Yang Zheng

Zhao Wang

YiBo Dong

Wantao Chen

Jiang Li

Weiming Chu

Wei Zhang

Yi Zhong

Li Mao

Xiaomeng Song

Yunong Wu

Affiliations

Soon will be listed here.

Abstract

Notch1 signaling is essential for tissue development and tumor progression. This signaling pathway has also been implicated in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). However, the role of Notch1 expression in OL and its malignant transformation is unknown. This study aimed to examine the Notch1 expression patterns by immunohistochemistry (IHC) in a cohort of 78 Chinese patients with OL and to analyze the relationship between the patterns and progression of OL to OSCC. Strong Notch1 staining was observed in 10 (13%) of the 78 OL patients, but it was not associated with any of the clinicopathological parameters. However, we observed membranous Notch1 expression in 24 (31%) of the OL samples. Membranous Notch1 expression was significantly associated with the severity of dysplasia (P<0.001) and development of OSCC (P=0.003). By multivariate analysis, membranous Notch1 expression was found to be the only independent factor for OSCC development in the patient population (P=0.019). Among the 24 patients with membranous Notch1 expression, 11 (46%) developed OSCC compared to 8 (15%) of the 54 patients without such expression (P=0.001, determined by log‑rank test). Furthermore, we established a 4‑nitroquinoline‑1‑oxide (4NQO)‑induced murine OSCC model and studied the Notch1 expression patterns in different stages of carcinogenesis. We observed that the extent of expression of membranous Notch1 increased during carcinogenesis. These data indicated a relationship between membranous Notch1 expression and OSCC risk in patients with OL and suggested that membranous Notch1 served as a biomarker for assessing OSCC risk.

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References

Miele L . Notch signaling. Clin Cancer Res. 2006; 12(4):1074-9. DOI: 10.1158/1078-0432.CCR-05-2570. View

Panelos J, Tarantini F, Paglierani M, Di Serio C, Maio V, Pellerito S . Photoexposition discriminates Notch 1 expression in human cutaneous squamous cell carcinoma. Mod Pathol. 2008; 21(3):316-25. DOI: 10.1038/modpathol.3801007. View

Cao W, Feng Z, Cui Z, Zhang C, Sun Z, Mao L . Up-regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma. Cancer. 2011; 118(11):2858-71. DOI: 10.1002/cncr.26575. View

Sun W, Gaykalova D, Ochs M, Mambo E, Arnaoutakis D, Liu Y . Activation of the NOTCH pathway in head and neck cancer. Cancer Res. 2013; 74(4):1091-104. PMC: 3944644. DOI: 10.1158/0008-5472.CAN-13-1259. View

Sakamoto K, Fujii T, Kawachi H, Miki Y, Omura K, Morita K . Reduction of NOTCH1 expression pertains to maturation abnormalities of keratinocytes in squamous neoplasms. Lab Invest. 2012; 92(5):688-702. DOI: 10.1038/labinvest.2012.9. View

Nicolas M, Wolfer A, Raj K, Kummer J, Mill P, van Noort M . Notch1 functions as a tumor suppressor in mouse skin. Nat Genet. 2003; 33(3):416-21. DOI: 10.1038/ng1099. View

Mitra D, Fernandez P, Bian L, Song N, Li F, Han G . Smad4 loss in mouse keratinocytes leads to increased susceptibility to UV carcinogenesis with reduced Ercc1-mediated DNA repair. J Invest Dermatol. 2013; 133(11):2609-2616. PMC: 3783584. DOI: 10.1038/jid.2013.213. View

Lodi G, Sardella A, Bez C, Demarosi F, Carrassi A . Interventions for treating oral leukoplakia. Cochrane Database Syst Rev. 2006; (4):CD001829. DOI: 10.1002/14651858.CD001829.pub3. View

Yao J, Duan L, Fan M, Wu X . Gamma-secretase inhibitors exerts antitumor activity via down-regulation of Notch and Nuclear factor kappa B in human tongue carcinoma cells. Oral Dis. 2007; 13(6):555-63. DOI: 10.1111/j.1601-0825.2006.01334.x. View

10.

Zheng Y, Wang Z, Ding X, Dong Y, Zhang W, Zhong Y . Combined Erlotinib and PF-03084014 treatment contributes to synthetic lethality in head and neck squamous cell carcinoma. Cell Prolif. 2017; 51(3):e12424. PMC: 6528911. DOI: 10.1111/cpr.12424. View

11.

Lee S, Do S, Lee H, Kang H, Koo B, Lim Y . Notch1 signaling contributes to stemness in head and neck squamous cell carcinoma. Lab Invest. 2016; 96(5):508-16. DOI: 10.1038/labinvest.2015.163. View

12.

Xu W, Liang C, Li Y, Ji Y, Qiu W, Tang X . Involvement of Notch1/Hes signaling pathway in ankylosing spondylitis. Int J Clin Exp Pathol. 2015; 8(3):2737-45. PMC: 4440088. View

13.

Hijioka H, Setoguchi T, Miyawaki A, Gao H, Ishida T, Komiya S . Upregulation of Notch pathway molecules in oral squamous cell carcinoma. Int J Oncol. 2010; 36(4):817-22. DOI: 10.3892/ijo_00000558. View

14.

Ranganathan P, Weaver K, Capobianco A . Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer. 2011; 11(5):338-51. DOI: 10.1038/nrc3035. View

15.

Duan L, Yao J, Wu X, Fan M . Growth suppression induced by Notch1 activation involves Wnt-beta-catenin down-regulation in human tongue carcinoma cells. Biol Cell. 2006; 98(8):479-90. DOI: 10.1042/BC20060020. View

16.

Schepman K, van der Meij E, Smeele L, van der Waal I . Malignant transformation of oral leukoplakia: a follow-up study of a hospital-based population of 166 patients with oral leukoplakia from The Netherlands. Oral Oncol. 1998; 34(4):270-5. View

17.

Hasina R, Martin L, Kasza K, Jones C, Jalil A, Lingen M . ABT-510 is an effective chemopreventive agent in the mouse 4-nitroquinoline 1-oxide model of oral carcinogenesis. Cancer Prev Res (Phila). 2009; 2(4):385-93. PMC: 2702843. DOI: 10.1158/1940-6207.CAPR-08-0211. View

18.

Sriuranpong V, Borges M, Ravi R, Arnold D, Nelkin B, Baylin S . Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res. 2001; 61(7):3200-5. View

19.

Artavanis-Tsakonas S, Rand M, Lake R . Notch signaling: cell fate control and signal integration in development. Science. 1999; 284(5415):770-6. DOI: 10.1126/science.284.5415.770. View

20.

Yuan P, Temam S, El-Naggar A, Zhou X, Liu D, Lee J . Overexpression of podoplanin in oral cancer and its association with poor clinical outcome. Cancer. 2006; 107(3):563-9. DOI: 10.1002/cncr.22061. View