Hes1 is involved in the self-renewal and tumourigenicity of stem-like cancer cells in colon cancer.

Hes1 is involved in the self-renewal and tumourigenicity of stem-like cancer cells in colon cancer.
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Hes1参与结肠癌干细胞样癌细胞的自我更新和致瘤性

DOI:
10.1038/srep03963
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发表时间:
2014-02-04
期刊:
影响因子:
4.6
通讯作者:
Xiao D
Xiao D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gao F;Zhang Y;Wang S;Liu Y;Zheng L;Yang J;Huang W;Ye Y;Luo W;Xiao D

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具有干细胞样特征的癌细胞的一小部分亚群可能负责肿瘤的产生、进展和化学抗性。Hes1影响某些干细胞和祖细胞以及消化系统的维持。我们发现,与分化良好的肿瘤样本相比,低分化癌样本中的Hes1表达上调,并且与在匹配的正常结肠样本中观察到的Hes1 mRNA相比,大多数腺癌显示出显著更高的Hes1 mRNA水平。此外,发现Hes1表达与结肠癌样品中干细胞标志物的表达相关,并且Hes1上调结肠癌细胞中干细胞相关基因的表达。此外,Hes1通过增加CD 133+细胞和SP细胞的大小以及肿瘤球形成的能力来增强干细胞样细胞的自我更新特性。此外,通过殖民地和软琼脂测定,Hes 1过表达细胞形成了显著更大和更高数量的菌落。更重要的是,Hes1增强结肠癌细胞系在裸鼠体内的致瘤性,在1 × 103细胞密度下表现出很强的成瘤能力。总之,我们的数据表明,Hes1诱导干细胞样细胞自我更新,并增加结肠癌中肿瘤起始细胞的数量。
A small subpopulation of cancer cells with stem cell-like features might be responsible for tumour generation, progression, and chemoresistance. Hes1 influences the maintenance of certain stem cells and progenitor cells and the digestive systems. We found upregulated Hes1 in poorly differentiated cancer samples compared with well-differentiated tumour samples, and most of the adenocarcinomas exhibited significantly higher levels of Hes1 mRNA compared with that observed in matched normal colon samples. Moreover, Hes1 expression was found to be correlated with the expression of stem cell markers in colon cancer samples, and Hes1 upregulates the expression of stemness-related genes in colon cancer cells. In addition, Hes1 enhances the self-renewal properties of the stem-like cells by increasing the sizes of CD133+ cells and SP cells and the ability of tumour sphere formation. Additionally, the Hes1-overexpressing cells formed significantly larger and higher number of colonies, as determined through the colony and the soft agar assays. More importantly, Hes1 enhances the tumourigenicity of colon cancer cell lines in nude mice and exhibits a strong tumour-formation ability at a cell density of 1 × 103. Taken together, our data indicate that Hes1 induces stem-like cell self-renewal and increases the number of tumour-initiating cells in colon cancer.
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