SIRT4 regulates cancer cell survival and growth after stress
SIRT4 regulates cancer cell survival and growth after stress
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DOI：
10.1016/j.bbrc.2016.01.078
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发表时间：
2016-02-05
影响因子：
3.1
通讯作者：
Seong, Rho Hyun
中科院分区：
文献类型：
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作者：
Jeong, Seung Min;Hwang, Sunsook;Seong, Rho Hyun
细胞应激启动协调良好的信号应答途径。由于对应激的适当调节对于细胞内稳态是必不可少的，因此应激反应途径的缺陷导致功能缺陷和细胞死亡。虽然线粒体SIRT4已被证明参与细胞应激反应和肿瘤抑制，但其在癌细胞存活和耐药性中的作用尚未得到很好的确定。在这里，我们表明SIRT4是癌细胞抗应激的关键调节因子。SIRT4被各种细胞应激高度诱导，并有助于应激后的细胞存活和生长。SIRT4缺失使细胞对DNA损伤或ER应激敏感。此外，SIRT4诱导是致瘤转化所必需的，因为SIRT4无效细胞易受癌基因激活的影响。因此，这些结果表明SIRT4在抗应激中具有重要作用，并且可能是癌症治疗的重要治疗靶点。(C)2016 Elsevier Inc. All rights reserved.
Cellular stresses initiate well-coordinated signaling response pathways. As the proper regulation of stress is essential for cellular homeostasis, the defects of stress response pathways result in functional deficits and cell death. Although mitochondrial SIRT4 has been shown to be involved in cellular stress response and tumor suppression, its roles in survival and drug resistance of cancer cells are not well determined. Here we show that SIRT4 is a crucial regulator of the stress resistance of cancer cells. SIRT4 is highly induced by various cellular stresses and contributes to cell survival and growth after stresses. SIRT4 loss sensitizes cells to DNA damage or ER stress. Moreover, SIRT4 induction is required for tumorigenic transformation, as SIRT4 null cells are vulnerable to oncogene activation. Thus, these results suggest that SIRT4 has essential roles in stress resistance and may be an important therapeutic target for cancer treatment. (C) 2016 Elsevier Inc. All rights reserved.