Coordes A, Zhifeng S, Sangvatanakul V, Qian X, Lenarz M, Kaufmann A M, Albers A E
Hals-, Nasen- und Ohrenklinik, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Deutschland.
HNO. 2014 Dec;62(12):867-72. doi: 10.1007/s00106-014-2931-4.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. HNSCC is caused by persistent high-risk human papillomavirus (HR-HPV) infection or excessive consumption of alcohol or tobacco. The persistently low survival rates result from local recurrences and metastases, which are probably caused by so-called tumor stem cells (TSCs). The epithelial-mesenchymal transition (EMT) or transformation is a key event in metastasis initiation and is being increasingly associated with TSCs.
This review describes new therapeutic targets in HNSCC, focusing on the TSC hypothesis and EMT regulation.
MATERIALS AND METHODS, RESULTS: TSCs and EMT are regulated directly and indirectly via transcription factors and microRNAs (miRNAs). These miRNAs regulate multiple cellular processes and may serve as new therapeutic targets, whose modulation could increase the effectiveness of HNSCC treatments. Post-transcriptionally, miRNAs regulate transcription factors associated with EMT (ZEB1/2, EZH2, Bmi-1), tumor suppressors (p53), TSC markers (ALDH, CD44, EpCAM, p63) and both epithelial (E-cadherin) and mesenchymal markers (vimentin).
Alterations in HNSSC TSC miRNA expression before and after chemotherapy could potentially serve as a therapeutic control. In the long term, knowledge of a patient's individual protein expression pattern may permit application of specific chemotherapy. Such individualized therapy might prohibit the development of metastases and potentially unresectable recurrences with a high resistance to radiation and chemotherapy, thus improving the prognosis in HNSCC patients.
头颈部鳞状细胞癌（HNSCC）是全球第六大常见癌症。HNSCC由持续性高危型人乳头瘤病毒（HR-HPV）感染或过量饮酒或吸烟引起。生存率持续低下是由局部复发和转移导致的，这可能是由所谓的肿瘤干细胞（TSC）引起的。上皮-间质转化（EMT）或转变是转移起始中的关键事件，并且越来越多地与TSC相关联。
本综述描述了HNSCC中的新治疗靶点，重点关注TSC假说和EMT调节。
材料与方法、结果：TSC和EMT通过转录因子和微小RNA（miRNA）直接和间接调节。这些miRNA调节多种细胞过程，并且可能作为新的治疗靶点，对其进行调节可以提高HNSCC治疗的有效性。在转录后水平，miRNA调节与EMT相关的转录因子（ZEB1/2、EZH2、Bmi-1）、肿瘤抑制因子（p53）、TSC标志物（醛脱氢酶、CD44、上皮细胞黏附分子、p63）以及上皮标志物（E-钙黏蛋白）和间质标志物（波形蛋白）。
化疗前后HNSSC TSC miRNA表达的改变可能潜在地用作治疗控制。从长远来看，了解患者的个体蛋白表达模式可能允许应用特定的化疗。这种个体化治疗可能会阻止转移的发生以及可能出现的对放疗和化疗具有高抗性的不可切除复发，从而改善HNSCC患者的预后。
