Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis of lung cancer

Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis of lung cancer
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癌症干细胞中转录因子 SOX2 的下调可抑制肺癌的生长和转移。

DOI:
10.1038/bjc.2011.210
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发表时间:
2011-06-07
影响因子:
8.8
通讯作者:
Luo, Y.
Luo, Y.
中科院分区:
医学1区
文献类型:
--
作者:
Xiang, R.;Liao, D.;Cheng, T.;Zhou, H.;Shi, Q.;Chuang, T. H.;Markowitz, D.;Reisfeld, R. A.;Luo, Y.

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背景:癌症干细胞假说认为肿瘤克隆仅由一小群细胞维持,这些细胞具有无限的增殖和分化潜力,并产生表型多样的癌细胞。癌症干细胞已被分离的能力外排Hoechst 33342染料,并被称为'侧人口'(SP)的方法和结果:Hoechst外排试验被用来分离和表征SP从小鼠D121肺癌细胞。在这里,我们证明了D121-SP细胞含有癌症干细胞特征,即,在D121-SP细胞中上调转录因子SOX 2和Oct 4。此外,敲低SOX 2基因后,D121-SP的迁移能力降低,凋亡率增加。重要的是,下调的SOX 2在D121细胞显着抑制其转移潜力在同基因mice.Conclusions:这些结果表明,SP是一个丰富的来源,肺肿瘤细胞的干细胞特性和SOX 2有一个重要的作用,在维持干细胞的特性和功能,可能是一个潜在的目标,有效的肺癌治疗。
Background:The cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a small subpopulation of cells, which have indefinite proliferation and differentiation potentials and give rise to phenotypically diverse cancer cells. Cancer stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the ‘side population’(SP).Methods and results:The Hoechst efflux assay was used to isolate and characterize the SP from murine D121 lung carcinoma cells. Here, we demonstrated that D121-SP cells contain cancer stem cell characteristics, that is, upregulation of the transcription factors SOX2 and Oct 4 in D121-SP cells. In addition, the migration of D121-SP was decreased, and apoptosis of D121-SP was upregulated following knocking down of SOX2 in D121 cells. Importantly, downregulation of SOX2 in D121 cells markedly suppressed their metastatic potential in syngeneic mice.Conclusions:These results suggest that the SP is an enriched source of lung tumour cells with stem cell properties and that SOX2 has an important role in maintaining stem cell properties and functions that may be a potential target for effective lung cancer therapy.
DOI: 10.1038/bjc.2011.94
发表时间: 2011-04-26
影响因子: 8.8
作者:
Xiang, R.;Liao, D.;Cheng, T.;Zhou, H.;Shi, Q.;Chuang, T. S.;Markowitz, D.;Reisfeld, R. A.;Luo, Y.
通讯作者: Luo, Y.