LOX is a novel mitotic spindle-associated protein essential for mitosis.
LOX is a novel mitotic spindle-associated protein essential for mitosis.
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DOI：
10.18632/oncotarget.8628
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发表时间：
2016-05-17
期刊：
影响因子：
--
通讯作者：
Kebebew E
中科院分区：
文献类型：
--
作者：
Boufraqech M;Wei D;Weyemi U;Zhang L;Quezado M;Kalab P;Kebebew E
LOX在多种人类恶性肿瘤中调节癌症进展。它在侵袭性癌症中过表达，LOX的较高表达与较高的癌症死亡率相关。在这里，我们报告了LOX在有丝分裂中的新功能。我们发现，LOX共定位于有丝分裂纺锤体从中期到末期，和p-H3（Ser 10）阳性细胞海港强LOX染色。此外，从同步化的细胞中纯化有丝分裂纺锤体显示LOX在诺考达唑存在下不能结合微管，而紫杉醇处理的样品显示LOX表达富集，表明LOX结合稳定的微管。LOX敲低导致G2/M期阻滞; p-H3（Ser 10）、细胞周期蛋白B1、CDK 1和Aurora B减少。此外，LOX敲低显著增加了癌细胞对靶向微管的化疗剂的敏感性。我们的研究结果表明，LOX在癌细胞有丝分裂中发挥作用，并可能被靶向增强微管抑制剂的活性，用于癌症治疗。
LOX regulates cancer progression in a variety of human malignancies. It is overexpressed in aggressive cancers and higher expression of LOX is associated with higher cancer mortality. Here, we report a new function of LOX in mitosis. We show that LOX co-localizes to mitotic spindles from metaphase to telophase, and p-H3(Ser10)-positive cells harbor strong LOX staining. Further, purification of mitotic spindles from synchronized cells show that LOX fails to bind to microtubules in the presence of nocodazole, whereas paclitaxel treated samples showed enrichment in LOX expression, suggesting that LOX binds to stabilized microtubules. LOX knockdown leads to G2/M phase arrest; reduced p-H3(Ser10), cyclin B1, CDK1, and Aurora B. Moreover, LOX knockdown significantly increased sensitivity of cancer cells to chemotherapeutic agents that target microtubules. Our findings suggest that LOX has a role in cancer cell mitosis and may be targeted to enhance the activity of microtubule inhibitors for cancer therapy.
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影响因子：
11.2
作者：
Nappi, Tito Claudio;Salerno, Paolo;Santoro, Massimo
通讯作者：
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44.1
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通讯作者：
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影响因子：
25.7
作者：
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通讯作者：
Neufeld, G