钙激活氯通道TMEM16A在头颈部鳞状细胞癌中的研究现状与进展

Recent status and progress of TMEM16A Ca^(2+)-activated chloride channel in head and neck squamous cell carcinoma

目的总结跨膜蛋白16A(TMEM16A)在头颈部鳞状细胞癌(HNSCC)中的研究现状,就临床预后、调控机制、癌症治疗、存在问题及未来研究方向进行系统综述,以期为TMEM16A在HNSCC的临床转化提供依据。方法以“跨膜蛋白16A、头颈部鳞状细胞癌、表皮生长因子受体、转化生长因子-β、免疫治疗”为中文关键词,以“transmembrane protein 16A(TMEM16A or ANO1)、head and neck squamous cell carcinoma、epidermal growth factor receptor、transforming growth factor-β、immunotherapy”为英文关键词,检索2006-01-01-2023-09-18中国知网及PubMed数据库发表的相关文献。纳入标准:(1)TMEM16A在HNSCC中的研究现状;(2)TMEM16A调控的表皮生长因子受体(EGFR)及转化生长因子-β(TGF-β)信号通路;(3)TMEM16A在抗肿瘤药物治疗中的研究现状。排除标准:(1)样本量小或数据不全的文献;(2)低质量文献;(3)综述文献。最终纳入50篇相关文献。结果TMEM16A高表达与HNSCC发生发展、低生存期及不良预后呈正相关。作为肿瘤促进因子,TMEM16A分别通过EGFR和TGF-β及其下游信号通路驱动HNSCC的生长和转移。TMEM16A抑制剂与HNSCC治疗药物的联合使用显著减少肿瘤生长。结论靶向TMEM16A的药物在HNSCC免疫治疗、靶向治疗和化学治疗中具有潜在价值。阐明TMEM16A在肿瘤免疫微环境中的作用是未来重要的研究方向。

Objective To summarize the current research progress of transmembrane protein 16A(TMEM16A)in head and neck squamous cell carcinoma(HNSCC),and systematically review the clinical prognosis,regulatory mechanisms,tumor therapy,existing issues,and future research directions in order to throw light on the clinical transformation of TMEM16A inHNSCC.Methodss Using"transmembrane protein 16A,ANO1,head and neck squamous cell carcinoma,epidermal growth factor receptor,transforming growth factor-β,immunotherapy"as keywords,relevant literature was searched in PubMed and CNKI databases from January 1,2006 to September 18,2023.Inclusion criteria:(1)the current state of TMEM16A in HNSCC;(2)epidermal growth factor receptor(EGFR)and transforming growth factor-β(TGF-β)signaling pathways that TMEM16A regulates;(3)the current status of TMEM16A in tumor therapy.Exclusion criteria:(1)literature with small sample size or incomplete data;(2)low quality literature;(3)reviews.Finally,50 related articles were included.Results High expression of TMEM16A is associated with HNSCC carcinogenesis and progression,poor prognosis,and short overall survival.As a tumor-promoting protein,TMEM16A stimulates cell proliferation through an EGFR-dependent signaling pathway and promotes metastasis through TGF-p.Tumor growth is dramatically reduced by combining TMEM16A inhibitors and HNSCC treatment medications.Conclusion TMEM16A-targeted drugs have promising potential values in chemotherapy,targeted treatment,and immunotherapy for HNSCC.Future research should focus on defining the role of TMEM16A in the tumor immune microenvironment.