Plasticity of lung cancer stem-like cells is regulated by the transcription factor HOXA5 that is induced by oxidative stress.
Plasticity of lung cancer stem-like cells is regulated by the transcription factor HOXA5 that is induced by oxidative stress.
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DOI：
10.18632/oncotarget.10571
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发表时间：
2016-08-02
期刊：
影响因子：
--
通讯作者：
Sato N
中科院分区：
文献类型：
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作者：
Saijo H;Hirohashi Y;Torigoe T;Horibe R;Takaya A;Murai A;Kubo T;Kajiwara T;Tanaka T;Shionoya Y;Yamamoto E;Maruyama R;Nakatsugawa M;Kanaseki T;Tsukahara T;Tamura Y;Sasaki Y;Tokino T;Suzuki H;Kondo T;Takahashi H;Sato N
癌症干细胞样细胞（CSC）/癌症起始细胞（CIC）是癌症治疗的合理靶点。然而，最近的研究表明，一些非CSC/CIC具有可塑性，可以去分化为CSC/CIC。因此，理解控制可塑性的分子机制对于实现CSC/CIC靶向治疗是至关重要的。在本研究中，我们分析了肺癌细胞的可塑性，发现肺非CSC/CIC可以去分化为CSC/CIC，这与干细胞转录因子SOX 2的表达一致。SOX 2的表达由转录因子HOXA 5诱导。氧化应激抑制HDAC 8的表达，然后诱导组蛋白3乙酰化，并增加HOXA 5和SOX 2的表达。这些发现表明肺癌细胞在氧化应激条件下具有可塑性，HOAX 5在去分化中具有关键作用。
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are reasonable targets for cancer therapy. However, recent studies have revealed that some non-CSCs/CICs have plastic ability and can dedifferentiate into CSCs/CICs. Therefore, an understanding of the molecular mechanisms that control the plasticity is essential to achieve CSC/CIC-targeting therapy. In this study, we analyzed the plasticity of lung cancer cells and found that lung non-CSCs/CICs can dedifferentiate into CSCs/CICs in accordance with the expression of stem cell transcription factor SOX2. SOX2 expression was induced by the transcription factor HOXA5. Oxidative stress repressed the expression of HDAC8 and then induced histone 3 acetylation and increased the expression of HOXA5 and SOX2. These findings indicate that lung cancer cells have plasticity under a condition of oxidative stress and that HOAX5 has a critical role in dedifferentiation.