Involvement of Polo-like kinase 1 (Plk1) in quiescence regulation of cancer stem-like cells of the gastric cancer cell lines.
Involvement of Polo-like kinase 1 (Plk1) in quiescence regulation of cancer stem-like cells of the gastric cancer cell lines.
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Polo 样激酶 1 (Plk1) 参与胃癌细胞系癌症干细胞的静止调节
DOI：
10.18632/oncotarget.16839
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发表时间：
2017-06-06
期刊：
影响因子：
--
通讯作者：
Yang WJ
中科院分区：
文献类型：
--
作者：
Zhu L;Xing S;Zhang L;Yu JM;Lin C;Yang WJ
肿瘤干细胞（CSC）被认为是肿瘤生长的启动细胞，对放化疗具有抵抗力，这些过程似乎与CSC的静止密切相关。在此，从人胃癌细胞系MKN 45和MKN 74获得具有高水平的CD44表达的CSC样细胞群。使用PKH26标记的保留试验，静止的CSC样细胞与低水平的Ki67和PCNA的表达被发现在无血清培养基中形成的球体，并表现出对药物和放射治疗的抗性。Polo样激酶1（Plk 1）和核糖体S6激酶1（RSK 1）在静止的CSC样细胞中被沉默。Plk 1特异性抑制剂抑制RSK 1的激活并诱导CSC样细胞的静止，但增加RSK 1活性并导致非CSC细胞的细胞凋亡。此外，抑制剂沉默RSK 1激活Plk 1，对CSC样细胞中球体的生长没有影响，但不影响Plk 1的磷酸化，导致非CSC中增殖减少。我们的研究结果表明，Plk 1和RSK 1在CSCs的活动和静止状态之间的转换中发挥重要作用。
Cancer stem cells (CSCs) have been hypothesized to initiate tumor growth and be resistant to chemoradiotherapy, and these processes appear to be closely related to CSC quiescence. Here, a CSC-like cell population with a high level of CD44 expression was obtained from the human gastric cancer cell lines MKN45 and MKN74. Using a PKH26-labeling retention assay, quiescent CSC-like cells with low levels of Ki67 and PCNA expression were found in spheres formed in serum-free medium, and exhibited resistance to drug and radiation treatments. Polo-like kinase 1 (Plk1) and ribosomal S6 kinase 1 (RSK1) were silenced in the quiescent CSC-like cells. The Plk1-specific inhibitors inhibited the activation of RSK1 and induced quiescence in the CSC-like cells, but increased RSK1 activity and resulted in apoptosis in non-CSCs. Furthermore, RSK1 silencing by inhibitors activated Plk1 and had no effect on the growth of spheres in the CSC-like cells, but did not affect phosphorylation of Plk1 and led to decreased proliferation in non-CSCs. Our results showed that Plk1 and RSK1 play important roles in the conversion of CSCs between active and quiescent states.
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