hes1-protein--human and Head-and-Neck-Neoplasms

The Notch signaling pathway has been associated with the regulation of self-renewal capacity, cell cycle exit, and survival. However, the relationship between the Notch signaling pathway and HNSCC remains controversial.. A meta-analysis was conducted to evaluate the role of Notch signaling pathway in HNSCC.. Relevant studies published until March 31, 2015 were identified by searching the PubMed, EMBASE and Ovid database.. A total of 9 articles were eligible for this meta-analysis. The meta-analysis results showed that the expression of Notch1, Notch3 and NICD was significantly higher in HNSCC as compared with control tissue. There was no significant difference in Jagged1 and HES1 expression between HNSCC and control tissue. Stratified analysis results showed that the expression of Notch1 was significantly higher in poor differentiation, III and IV stage and positive lymph node metastasis patients. Additionally, over-expression of Notch1, NICD, HES1 and DLL4 significantly predicted poor OS in HNSCC patients.. The Notch signaling pathway plays an important role in tumor development of HNSCC. Inhibition of the Notch signaling pathway is a potential therapeutic method of HNSCC.

Topics: Adaptor Proteins, Signal Transducing; Calcium-Binding Proteins; Carcinoma, Squamous Cell; Cell Differentiation; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Intercellular Signaling Peptides and Proteins; Jagged-1 Protein; Neoplasm Staging; Odds Ratio; Receptor, Notch1; Receptors, Notch; Risk Factors; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; Survival Analysis; Time Factors; Transcription Factor HES-1

Head and neck squamous cell carcinoma (HNSCC), a common cancer worldwide, is etiologically associated with tobacco use, high alcohol consumption, and high-risk human papillomaviruses (HPV). The Notch signaling pathway, which is involved in cell differentiation decisions with differential downstream targets and effects depending on tissue type and developmental stage, has been implicated in human HNSCC.. To assess the role of Notch signaling in HPV-positive and HPV-negative HNSCC, we utilized genetically engineered mouse (GEM) models for conventional keratinizing HNSCC, in which either HPV16 E6 and E7 oncoproteins or a gain-of-function mutant p53 are expressed, and in which we inactivated canonical Notch signaling via expression of a dominant negative form of MAML1 (DNMAML1), a required transcriptional coactivator of Notch signaling.. Loss of canonical Notch signaling increased tumorigenesis in both contexts and also caused an increase in nuclear β-catenin, a marker for increased tumorigenic potential. When combined with loss of canonical Notch signaling, HPV oncogenes led to the highest frequency of cancers overall and the largest number of poorly differentiated (high-grade) cancers.. These findings inform on the contribution of loss of canonical Notch signaling in head and neck carcinogenesis.

Topics: Animals; Cell Transformation, Neoplastic; Cell Transformation, Viral; Disease Models, Animal; DNA-Binding Proteins; Female; Gene Expression; Head and Neck Neoplasms; Human papillomavirus 16; Humans; Male; Mice; Mice, Transgenic; Molecular Targeted Therapy; Oncogene Proteins, Viral; Papillomavirus E7 Proteins; Papillomavirus Infections; Receptors, Notch; Repressor Proteins; Severity of Illness Index; Signal Transduction; Transcription Factor HES-1; Transcription Factors