GLI-mediated Keratin 17 expression promotes tumor cell growth through the anti-apoptotic function in oral squamous cell carcinomas
GLI-mediated Keratin 17 expression promotes tumor cell growth through the anti-apoptotic function in oral squamous cell carcinomas
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DOI：
10.1007/s00432-017-2398-2
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发表时间：
2017-03
影响因子：
3.6
通讯作者：
Y. Mikami;S. Fujii;K. Nagata;H. Wada;Kana Hasegawa;Misaki Abe;Reiko U. Yoshimoto;S. Kawano;
中科院分区：
文献类型：
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作者：
Y. Mikami;S. Fujii;K. Nagata;H. Wada;Kana Hasegawa;Misaki Abe;Reiko U. Yoshimoto;S. Kawano;
目的角蛋白17（KRT 17）被认为是口腔鳞状细胞癌（OSCC）的潜在诊断标志物。方法采用免疫组织化学方法检测KRT 17、GLI家族锌指蛋白（GLI）-1、GLI-2和caspase-3在口腔鳞癌中的表达。在OSCC细胞系中研究了KRT 17、GLI-1或GLI-2的表达，并使用siRNA或抑制剂研究了KRT 17或GLI功能丧失的影响，结果78例口腔鳞癌患者的组织标本的免疫组化分析显示，KRT 17在非口腔鳞癌组织中未被观察到。在肿瘤区域中表达，但在肿瘤区域中以高频率强烈表达。敲除KRT 17增加了裂解的半胱天冬酶-3阳性细胞的数量，导致细胞数量减少。GLI-1或GLI-2的功能丧失还增加了Annexin-V和碘化丙啶（PI）染色和末端脱氧核苷酸转移酶dUTP-生物素缺口末端标记（TUNEL）法阳性的凋亡细胞的细胞数量，并诱导DNA片段化。外源KRT 17表达部分挽救了这种对细胞生长的抑制作用。结论KRT 17在口腔鳞癌中的表达可能与GLI-1或GLI-2的过度表达有关。
PurposeKeratin 17 (KRT17) has been suggested as a potential diagnostic marker of squamous cell carcinoma including oral squamous cell carcinoma (OSCC). The current study was conducted to clarify the function of KRT17 and its expression mechanism in OSCC.MethodsImmunohistochemical analyses were carried out to examine the expression of KRT17, GLI family zinc finger (GLI)-1, GLI-2, or cleaved caspase-3 in OSCCs. The expression of KRT17, GLI-1, or GLI-2 was investigated among OSCC cell lines, and the effects of loss-of-function of KRT17 or GLI, using siRNA or inhibitor, on the cell growth of the OSCC cell line HSC-2 particularly with respect to apoptosis were examined.ResultsImmunohistochemical analyses of tissue specimens obtained from 78 OSCC patients revealed that KRT17 was not observed in non-tumor regions but was strongly expressed at high frequencies in tumor regions. Knockdown of KRT17 increased the number of cleaved caspase-3-positive cells, leading to the reduction of cell number. Loss-of-function of GLI-1 or GLI-2 also increased the cell numbers of apoptotic cells positive for staining of Annexin-V and propidium iodide (PI) and the terminal deoxynucleotidyl transferase dUTP-biotin nick-end labeling (TUNEL) method, and induced DNA fragmentation. This inhibitory effect on cell growth was partially rescued by exogenous KRT17 expression. In the KRT17-positive regions in OSCCs, GLI-1 or GLI-2 was frequently detected, and the number of cells with cleaved caspase-3 positive was decreased.ConclusionsKRT17 promotes tumor cell growth, at least partially, through its anti-apoptotic effect as a result of the KRT17 overexpression by GLIs in OSCC.