Role of the IL-6-JAK1-STAT3-Oct-4 pathway in the conversion of non-stem cancer cells into cancer stem-like cells.
Role of the IL-6-JAK1-STAT3-Oct-4 pathway in the conversion of non-stem cancer cells into cancer stem-like cells.
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DOI：
10.1016/j.cellsig.2013.01.007
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发表时间：
2013-04
影响因子：
4.8
通讯作者：
Lee YJ
中科院分区：
文献类型：
--
作者：
Kim SY;Kang JW;Song X;Kim BK;Yoo YD;Kwon YT;Lee YJ
先前的研究表明，一小部分癌细胞能够形成肿瘤。肿瘤启动性肿瘤干细胞（CSCs）的存在对未来的癌症治疗和治疗具有重要意义。然而，最近一些研究人员提出，分化的癌细胞（非cscs）可以转化为干细胞样细胞以维持平衡。这些结果表明，去除CSCs可能会促使肿瘤中的非CSCs转化为干细胞以维持平衡。白细胞介素-6 （IL-6）在CSCs的诱导形成及其与非干细胞的动态平衡中起着重要作用。在这项研究中，我们使用csc样人乳腺癌细胞及其替代亚群非csc来研究IL-6如何调节非csc向csc的转化。MDA-MB-231和MDA-MB-453 csc样细胞能很好地形成乳腺球，而大多数非干细胞因细胞凋亡而死亡，只有部分剩余的非干细胞能形成存活的乳腺球。在异种移植物肿瘤形成中也观察到类似的结果。细胞因子阵列分析结果显示，在超低贴壁培养皿中，非csc细胞分泌IL-6。IL-6在非csc中通过IL-6- jak1 - stat3信号转导途径调控csc相关OCT-4基因的表达。抗il -6抗体（1 μg/ml）或氯硝柳胺(0.5-2 μM)/LLL12 （5-10 μM）抑制该通路可有效抑制OCT-4基因的表达。这些结果表明，IL-6-JAK1-STAT3信号转导通路通过调控OCT-4基因的表达，在非CSCs向CSCs转化过程中发挥了重要作用。
Previous studies have demonstrated that a small subset of cancer cells is capable of tumor initiation. The existence of tumor initiating cancer stem cells (CSCs) has several implications in terms of future cancer treatment and therapies. However, recently, several researchers proposed that differentiated cancer cells (non-CSCs) can convert to stem-like cells to maintain equilibrium. These results imply that removing CSCs may prompt non-CSCs in the tumor to convert into stem cells to maintain the equilibrium. Interleukin-6 (IL-6) has been found to play an important role in the inducible formation of CSCs and their dynamic equilibrium with non-stem cells. In this study, we used CSC-like human breast cancer cells and their alternate subset non-CSCs to investigate how IL-6 regulates the conversion of non-CSCs to CSCs. MDA-MB-231 and MDA-MB-453 CSC-like cells formed mammospheres well, whereas most of non-stem cells died by anoikis and only part of the remaining non-stem cells produced viable mammospheres. Similar results were observed in xenograft tumor formation. Data from cytokine array assay show that IL-6 was secreted from non-CSCs when cells were cultured in ultra-low attachment plates. IL-6 regulates CSC-associated OCT-4 gene expression through the IL-6-JAK1-STAT3 signal transduction pathway in non-CSCs. Inhibiting this pathway by treatment with anti-IL-6 antibody (1 μg/ml) or niclosamide (0.5–2 μM)/LLL12 (5–10 μM) effectively prevented OCT-4 gene expression. These results suggest that the IL-6-JAK1-STAT3 signal transduction pathway plays an important role in the conversion of non-CSCs into CSCs through regulation of OCT-4 gene expression.
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DOI：
10.1186/bcr1680
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Berishaj M;Gao SP;Ahmed S;Leslie K;Al-Ahmadie H;Gerald WL;Bornmann W;Bromberg JF
通讯作者：
Bromberg JF
影响因子：
11.5
作者：
Duan, Zhenfeng;Bradner, James E.;Seiden, Michael V.
通讯作者：
Seiden, Michael V.
DOI：
10.1098/rstb.1996.0012
发表时间：
1996-02-29
影响因子：
6.3
作者：
Ihle, JN
通讯作者：
Ihle, JN
影响因子：
56.9
作者：
Darnell, JE
通讯作者：
Darnell, JE
影响因子：
3.7
作者：
Azare, Janeen;Doane, Ashley;Bromberg, Jacqueline
通讯作者：
Bromberg, Jacqueline