Abstract
Therapeutic outcome in head and neck squamous cell carcinoma (HNSCC) is poor in most advanced cases. To improve therapeutic efficiency, novel therapeutic targets and prognostic factors must be discovered. Our studies have identified several G protein-coupled receptors (GPCRs) as promising candidates. Significant epigenetic silencing of GPCR expression occurs in HNSCC compared with normal tissue, and is significantly correlated with clinical behavior. Together with the finding that GPCR activity can suppress tumor cell growth, this indicates that GPCR expression has potential utility as a prognostic factor. In this review, we discuss the roles that galanin receptor type 1 (GALR1) and type 2 (GALR2), tachykinin receptor type 1 (TACR1), and somatostatin receptor type 1 (SST1) play in HNSCC. GALR1 inhibits proliferation of HNSCC cells though ERK1/2-mediated effects on cell cycle control proteins such as p27, p57, and cyclin D1, whereas GALR2 inhibits cell proliferation and induces apoptosis in HNSCC cells. Hypermethylation of GALR1, GALR2, TACR1, and SST1 is associated with significantly reduced disease-free survival and a higher recurrence rate. Although their overall activities varies, each of these GPCRs has value as both a prognostic factor and a therapeutic target. These data indicate that further study of GPCRs is a promising strategy that will enrich pharmacogenomics and prognostic research in HNSCC.
Highlights
Head and neck carcinomas are defined as carcinomas of head and neck regions including pharynx, larynx, the tongue, oral cavity, nasal cavity and paranasal cavity
head and neck squamous cell carcinoma (HNSCC) cells, we showed that galanin receptor type 1 (GALR1) signaling inhibits cell proliferation (Figure 1A) and colony formation (Figure 1B), which is associated with ERK1/2 activation (Figure 1C)
The disease-free survival (DFS) of the patients with both SSTR1 and GALR1 methylation was significantly higher than that of patients without methylation of these genes [80]. These data indicate that SST and SSTR1 gene inactivation via CpG hypermethylation plays a role during HNSCC tumorigenesis, and that this methylation level may serve as a significant biomarker
Summary
Head and neck carcinomas are defined as carcinomas of head and neck regions including pharynx, larynx, the tongue, oral cavity, nasal cavity and paranasal cavity They are usually characterized histopathologically as squamous cell carcinomas. Current standard treatments for head and neck squamous cell carcinomas (HNSCC) are aggressive and multimodal treatments including surgery, radiotherapy, and chemotherapy. Despite these aggressive treatments, long-term survival rates are poor and remain between 40% and 50% [1,2,3]. To improve the survival rate of HNSCC patients, there is a requirement for novel treatment strategies that are less toxic, and that can improve survival in the long term This creates the need for development of new drugs and identification of novel biomarkers. We discuss results of studies on several GPCRs, and discuss the future direction of GPCR-focused studies in HNSCC
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