CYLD的主要生物功能是去掉一些重要底物分子如Traf2/6, Bcl3, Nemo等的泛素而改变它们的功能。CYLD通过负调控一些致肿瘤分子信号传导如NF-kB,TGF-β,WNT,Bcl3,JNK等导致细胞增殖抑制。我们前期的实验显示小鼠CYLD缺失导致致癌剂诱导的小鼠皮肤鳞状细胞癌癌症干细胞增多并有较强的致肿瘤特征。CYLD是否通过影响癌症干细胞的自我更新和分化而抑制皮肤癌的生长未见报道。我们将用流式细胞仪分离肿瘤组织中CD34highа6 integrinhighN-cadherinhigh癌症干细胞以观察它们在免疫缺陷小鼠中的致肿瘤特征和在有或无CYLD存在时的区别。我们将用免疫荧光染色方法对皮肤癌细胞系中对称和非对称细胞分裂进行检测以探讨CYLD缺失时癌症干细胞增多的分子机制。此外，还用免疫组化方法检测CYLD在人皮肤癌组织的表达并研究其与临床病理分化程度、预后和转移癌的关系。

The major function of CYLD is to remove ubiquitin from its substrates such as Traf 2/6, Bcl3, and Nemo and modify their functions. CYLD is recognized as a critical tumor suppressor since it negatively regulates oncogenic pathways such as NF-kB, TGF-beta, WNT, Bcl3, JNK and leads to suppression of tumor growth. Our preliminary study shows that loss of CYLD leads to an increase number of cancer stem cells (CSCs) and the CSCs are more tumorigenic. However, whether CYLD inhibits the SCC progression by affecting the selfrenewal and differentiation of CSCs is unknown. In order to study the CYLD regulations on CSCs by in vivo and in vitro assays, we will isolate CD34high а6 integrinhigh N-cadherinhigh/low CSCs with or without CYLD expression from squamous cell carcinoma (SCC) tissues and compare their in vivo tumor initiating effect in immune-compromised nude mice. We will determine the symmetrical and asymmetrical cell divisions by immune fluorescence to explore the mechanisms of CYLD effect on CSCs. Moreover, the CYLD expression in human SCC tissues and their correlations with pathological stages, prognosis, and metastasis will be studied.