G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer?
G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer?
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DOI：
10.3390/toxins7082959
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发表时间：
2015-08-05
期刊：
影响因子：
4.2
通讯作者：
Carey TE
中科院分区：
文献类型：
--
作者：
Kanazawa T;Misawa K;Misawa Y;Uehara T;Fukushima H;Kusaka G;Maruta M;Carey TE
头颈部鳞状细胞癌（HNSCC）的治疗效果在大多数晚期病例中都很差。为了提高治疗效率，必须发现新的治疗靶点和预后因素。我们的研究已经确定了几种G蛋白偶联受体（gpcr）作为有希望的候选者。与正常组织相比，HNSCC中GPCR表达的表观遗传沉默显著，且与临床行为显著相关。再加上发现GPCR活性可以抑制肿瘤细胞生长，这表明GPCR表达作为预后因素具有潜在的效用。本文就甘丙肽受体1型（GALR1）和2型（GALR2）、速激肽受体1型（TACR1）和生长抑素受体1型（SST1）在HNSCC中的作用进行综述。GALR1通过erk1 /2介导的对细胞周期控制蛋白如p27、p57和cyclin D1的作用抑制HNSCC细胞的增殖，而GALR2抑制HNSCC细胞的增殖并诱导细胞凋亡。GALR1、GALR2、TACR1和SST1的高甲基化与显著降低的无病生存期和更高的复发率相关。尽管它们的总体活性各不相同，但每种gpcr都具有作为预后因素和治疗靶点的价值。这些数据表明，进一步研究gpcr是一种有前途的策略，将丰富HNSCC的药物基因组学和预后研究。
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.