JCI：我科学家人类肝癌干细胞自我更新机制

2015-09-07 佚名生物谷

近日，来自中科院生物物理所的范祖森研究小组在国际学术期刊JCI上发表了一项最新研究进展，他们在肝癌干细胞中发现转录因子ZIC2表达水平较高，并对其维持肝癌干细胞自我更新的作用机制进行了研究。肝细胞癌（HCC）是全世界最常见的癌症类型之一，复发率高和肿瘤异质性是这种癌症的两个主要特征。近年来一些研究提出癌症干细胞模型，他们发现一小群具有自我更新能力的癌症干细胞能够分化形成新的肿瘤细胞，并认为癌症干细

近日，来自中科院生物物理所的范祖森研究小组在国际学术期刊JCI上发表了一项最新研究进展，他们在肝癌干细胞中发现转录因子ZIC2表达水平较高，并对其维持肝癌干细胞自我更新的作用机制进行了研究。

肝细胞癌（HCC）是全世界最常见的癌症类型之一，复发率高和肿瘤异质性是这种癌症的两个主要特征。近年来一些研究提出癌症干细胞模型，他们发现一小群具有自我更新能力的癌症干细胞能够分化形成新的肿瘤细胞，并认为癌症干细胞是维持肿瘤生长以及对传统治疗方法产生抵抗的重要原因。尽管目前已经能够通过一些表面标记对肝癌干细胞进行富集，但是人们对于肝癌干细胞的了解仍然不足。

在这项研究中，研究人员对肝癌干细胞和普通HCC细胞的转录组表达谱进行了分析,结果发现转录因子ZIC2在肝癌干细胞中表达水平很高。他们发现ZIC2对于肝癌干细胞的自我更新具有非常重要的作用，删除ZIC2能够显著减弱肝癌干细胞的球体形成（sphere formation）能力，并可以抑制移植瘤在小鼠体内的生长。

随后，研究人员对ZIC2的作用机制进行了探究，他们发现ZIC2作用于转录因子OCT4的上游，ZIC2能够将核重塑因子复合体NURF招募到OCT4的启动子区域，进而起始OCT4的转录激活。研究人员在HCC病人中发现NURF复合体的表达水平与HCC的临床进展和预后呈现一致性，并且ZIC2和OCT4的表达水平与HCC病人所处的临床病理学阶段成正相关性。

总的来说，这项研究表明转录因子ZIC2,OCT4以及核重塑因子复合物NURF可以作为HCC疾病诊断标记并可预测HCC病人的预后情况，同时这三个因子还可以作为根除肝癌干细胞的潜在靶向目标在HCC的治疗中发挥重要作用。

原文出处：

Pingping Zhu1, Yanying Wang1,et al.ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells.JCI.2015

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2015-10-26 hmwwww

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2016-01-22 caobinglei8079

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2015-09-10 he408015781

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期待进一步的研究

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2015-09-09 1249898am19暂无昵称

#癌干细胞#

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