背景:由于已知苦味受体(TAS2R)在各种口外细胞中表达并具有功能活性,它们的遗传变异性和由它们的激活引发的功能反应已经引起了更广泛的兴趣,包括在癌症的背景下。
方法:在PubMed和GoogleScholar中进行了一项系统研究,以确定有关TAS2R在癌症中的作用的相关出版物。
结果:虽然关于TAS2R基因型和表型的变异及其与患癌症风险的关系的发现仍然没有定论,基因表达分析显示,与非癌细胞系和组织样品相比,TAS2R表达,并且其中一些在癌性细胞中主要下调。此外,受体特异性,激动剂介导的激活诱导各种抗癌作用,如细胞增殖减少,迁移,和入侵,以及增加细胞凋亡。此外,在一项体内研究中,TAS2R的过表达导致肿瘤发病率降低,而TAS2R的激活甚至可以增强体外化疗药物的治疗效果.最后,TAS2R在原发性癌细胞和组织中的较高表达水平与人类预后改善相关.
结论:由于目前的证据表明TAS2R在癌变中的功能作用,进一步的研究应该利用它们作为化疗药物(联合)靶点的潜力.
BACKGROUND: Since it is known that bitter taste receptors (
TAS2Rs) are expressed and functionally active in various extra-oral cells, their genetic variability and functional response initiated by their activation have become of broader interest, including in the context of cancer.
METHODS: A systematic research was performed in PubMed and Google Scholar to identify relevant publications concerning the role of
TAS2Rs in cancer.
RESULTS: While the findings on variations of TAS2R genotypes and phenotypes and their association to the risk of developing cancer are still inconclusive, gene expression analyses revealed that TAS2Rs are expressed and some of them are predominately downregulated in cancerous compared to non-cancerous cell lines and tissue samples. Additionally, receptor-specific, agonist-mediated activation induced various anti-cancer effects, such as decreased cell proliferation, migration, and invasion, as well as increased apoptosis. Furthermore, the overexpression of
TAS2Rs resulted in a decreased tumour incidence in an in vivo study and TAS2R activation could even enhance the therapeutic effect of chemotherapeutics in vitro. Finally, higher expression levels of
TAS2Rs in primary cancerous cells and tissues were associated with an improved prognosis in humans.
CONCLUSIONS: Since current evidence demonstrates a functional role of
TAS2Rs in carcinogenesis, further studies should exploit their potential as (co-)targets of chemotherapeutics.