The Notch pathway promotes the cancer stem cell characteristics of CD90+ cells in hepatocellular carcinoma.
The Notch pathway promotes the cancer stem cell characteristics of CD90+ cells in hepatocellular carcinoma.
复制标题
Notch通路促进肝细胞癌中CD90细胞的癌症干细胞特性。
DOI：
10.18632/oncotarget.6672
复制
发表时间：
2016-02-23
期刊：
影响因子：
--
通讯作者：
Cheng B
中科院分区：
文献类型：
--
作者：
Luo J;Wang P;Wang R;Wang J;Liu M;Xiong S;Li Y;Cheng B
CD90已被确定为肝癌干细胞（CSCs）的一个标志物，它负责致瘤活性，但CD90+细胞如何促进肿瘤的发生和进展尚不清楚。我们的数据表明，CD90在肝细胞癌（HCC）组织中的高表达与HCC患者的静脉滤过有关。从HCC细胞系中分离的CD90+细胞表现出增强的致瘤性、化疗耐药、肿瘤侵袭和转移。Notch通路在CD90+细胞中被激活，我们发现在CD90+ CSCs中抑制Notch通路可降低致瘤性、细胞侵袭、迁移和干细胞相关基因的表达。CD90−细胞中Notch通路的激活诱导自我更新、侵袭和迁移。此外，我们观察到，通过刺激细胞周期期G1-S转变和抑制Notch通路介导的细胞凋亡，促进了癌症干细胞的特征。我们的研究结果表明，CD90可以作为HCC CSCs的潜在生物标志物，并且在CD90+ CSCs中，通过上激活的Notch通路，癌症干细胞活性升高。
CD90 has been identified as a marker for liver cancer stem cells (CSCs) that are responsible for tumorigenic activity, but it is not known how CD90+ cells contribute to tumor initiation and progression. Our data demonstrated that high expression of CD90 in Hepatocellular Carcinoma (HCC) tissues correlated with venous filtration in HCC patients. CD90+ cells isolated from HCC cell lines exhibited increased tumorigenicity, chemoresistance, tumor invasion and metastasis. Notch pathway was activated in CD90+ cells and we found that inhibition of Notch pathway in CD90+ CSCs decreased tumorigenicity, cell invasion, migration and expression of stem cell related genes. Activation of Notch pathway in CD90− cells induced self-renewal, invasion and migration. Furthermore, we observed that cancer stem cell features were facilitated by stimulating G1-S transition in the cell cycle phase and inhibiting apoptosis mediated by Notch pathway. Our findings suggested CD90 could be used as a potential biomarker for HCC CSCs, and that cancer stem cell activity was elevated through up activated Notch pathway in CD90+ CSCs.