E3-ligase Skp2 predicts poor prognosis and maintains cancer stem cell pool in nasopharyngeal carcinoma.
E3-ligase Skp2 predicts poor prognosis and maintains cancer stem cell pool in nasopharyngeal carcinoma.
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E3-连接酶 Skp2 预测鼻咽癌不良预后并维持癌症干细胞库
DOI：
10.18632/oncotarget.2149
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发表时间：
2014-07-30
期刊：
影响因子：
--
通讯作者：
Liu QQ
中科院分区：
文献类型：
--
作者：
Wang J;Huang Y;Guan Z;Zhang JL;Su HK;Zhang W;Yue CF;Yan M;Guan S;Liu QQ
鼻咽癌（NPC）是严重的头颈癌之一，在西方国家很少见，但在南亚特别是华南地区发病率较高。尽管鼻咽癌对放疗相对敏感，但由于诊断时已属晚期，患者预后较差。因此，了解肿瘤发生的机制并开发早期诊断技术非常重要。 S 期激酶相关蛋白 2 (Skp2) 在多种人类癌症中过度表达，并与不良预后相关。然而，其在 NPC 中的功能尚未得到充分解决。在这项研究中，我们发现 Skp2 在鼻咽癌标本中高表达，并且与不良预后相关。我们生成了 Skp2 敲低细胞，以进一步描述其在 NPC 发育中的作用。 Skp2的敲低部分减少了细胞增殖，促进了细胞衰老，并减少了醛脱氢酶1阳性细胞等干细胞的数量及其自我更新能力。我们的研究不仅解释了Skp2在鼻咽癌患者不良预后中的预测作用，而且揭示了Skp2调节鼻咽癌干细胞的维持，为临床应用中鼻咽癌的靶向治疗和早期诊断提供依据。
Nasopharyngeal carcinoma (NPC) is one of the severe head and neck carcinomas, which is rare in west countries but has high incidence in Southern Asia especially South China. Although NPC is relatively sensitive to radiotherapy, the prognosis of patients is poor due to the advanced stage at the time of diagnosis. Therefore, it is important to understand the mechanisms involved in tumorigenesis and develop early diagnostic techniques. S-phase kinase associated protein 2 (Skp2) is overexpressed in several human cancers and associates with poor prognosis. However, its function in NPC has not been fully addressed. In this study we found Skp2 was highly expressed in NPC specimen and correlated with poor prognosis. We generated Skp2 knockdown cells to further delineate its role in NPC development. Knockdown of Skp2 partially reduced cell proliferation, promoted cellular senescence, and decreased the population of stem cell like aldehyde dehydrogenase1 positive cells as well as their self-renewal ability. Our study not only interprets the predictive role of Skp2 in the poor prognosis of NPC patients, but also reveals that Skp2 regulates the NPC cancer stem cell maintenance, which shed lights on the target therapy and early diagnosis of NPC in clinical application.
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