LZTS2 inhibits PI3K/AKT activation and radioresistance in nasopharyngeal carcinoma by interacting with p85
LZTS2 inhibits PI3K/AKT activation and radioresistance in nasopharyngeal carcinoma by interacting with p85
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LZTS2 通过与 p85 相互作用抑制鼻咽癌中 PI3K/AKT 的激活和放射抗性
DOI：
10.1016/j.canlet.2018.01.067
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Yang, Kunyu
中科院分区：
文献类型：
--
作者：
Xu, Shuangbing;Li, Yan;Yang, Kunyu
磷脂酰肌醇3-激酶(PI3K)活性在鼻咽癌中异常激活。然而，潜在的机制仍不清楚。在这里，我们发现亮氨酸拉链肿瘤抑制因子2(LZTS2)表达下调，并预测鼻咽癌患者的预后不良。此外，我们用无偏倚的蛋白质组学方法鉴定了PI3K亚基P85是一种新的LZTS2相互作用蛋白。此外，我们还证明了LZTS2与p110竞争P85结合，并抑制PI3K/AKT信号通路的激活。在功能上，我们发现LZTS2以P85依赖的方式抑制鼻咽癌的肿瘤发生和放射抵抗。综上所述，我们的结果不仅提供了PI3K/AKT信号被激活的分子机制，而且提示靶向LZTS2/PI3K/AKT信号轴是鼻咽癌放射增敏的一种有前景的治疗策略。(C)2018爱思唯尔B.V.保留所有权利。
Phosphoinositide 3-kinase (PI3K) activity is aberrantly activated in nasopharyngeal carcinoma. However, the underlying mechanisms remain unclear. Here, we found that Leucine zipper tumor suppressor 2 (LZTS2) was downregulated and predicted poor prognosis in nasopharyngeal carcinoma patients. Furthermore, we identified the PI3K subunit p85 as a novel LZTS2-interacting protein using an unbiased proteomics approach. Moreover, we demonstrated that LZTS2 competes with p110 for p85 binding and inhibits activation of the PI3K/AKT signaling pathway. Functionally, we showed that LZTS2 suppresses tumorigenesis and radioresistance in nasopharyngeal carcinoma in a p85-dependent manner. Taken together, our results not only provide understanding of the molecular mechanisms by which PI3K/AKT signaling is activated but also suggest that targeting the LZTS2/PI3K/AKT signaling axis is a promising therapeutic strategy for radiosensitization of nasopharyngeal carcinoma. (C) 2018 Elsevier B.V. All rights reserved.