Extracellular HMGB1 prevents necroptosis in acute myeloid leukemia cells
Extracellular HMGB1 prevents necroptosis in acute myeloid leukemia cells
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细胞外 HMGB1 预防急性髓系白血病细胞坏死性凋亡
DOI：
10.1016/j.biopha.2019.108714
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发表时间：
2019-04-01
影响因子：
7.5
通讯作者：
Yang, Minghua
中科院分区：
文献类型：
--
作者：
Liu, Yingting;Chen, Pan;Yang, Minghua
高迁移率族蛋白1(HMGB1)是一种损伤相关分子模式(DAMP)分子，其表达和亚细胞定位的变化与肿瘤的发生和肿瘤细胞的死亡有关。具体地说，HMGB1的释放已经被证明发生在一种被称为坏死性下垂的特定形式的诱导细胞死亡中。在本研究中，我们研究了HMGB1在急性髓系白血病(AML)细胞坏死性下垂中的作用。在两个AML细胞系和两个患者的原代AML细胞中，当Caspase活性被Z-VAD-fmk抑制时，依托泊苷通过cIAP1/2降解诱导坏死性下垂，但细胞外HMGB1处理可阻止这种坏死性下垂。有趣的是，HMGB1并没有阻止cIAP1/2的降解，而是激活了核因子kappa B途径。本研究结果表明，细胞外HMGB1不仅是细胞坏死时释放的重要湿性分子，也是预防AML细胞坏死性下垂的调节因子。
Changes in the expression and subcellular localization of high mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, have been implicated in tumorigenesis and tumor cell death in response to cancer therapy. Specifically, HMGB1 release has been shown to occur with a specific form of induced cell death known as necroptosis. In the present study, we examined the role of HMGB1 in the necroptosis of acute myeloid leukemia (AML) cells. In two AML cell lines and primary AML cells from two patients, etoposide induced necroptosis via cIAP1/2 degradation when caspase activity was inhibited by Z-VAD-fmk, but treatment with extracellular HMGB1 prevented this necroptosis. Interestingly, HMGB1 did not prevent the degradation of cIAP1/2, but rather activated the nuclear factor kappa B pathway. The results of the present study provide evidence that extracellular HMGB1 is not only an important DAMP molecule released by cells upon necrosis, but also a regulatory factor that prevents necroptosis in AML cells.