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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >NF-κB-mediated repression of growth arrest- and DNA-damage-inducible proteins 45α and γ is essential for cancer cell survival
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NF-κB-mediated repression of growth arrest- and DNA-damage-inducible proteins 45α and γ is essential for cancer cell survival

机译：NF-κB介导的抑制生长停滞和DNA损伤诱导蛋白45α和γ对癌细胞存活至关重要

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摘要

The NF-κB/IκB signaling pathway is a critical regulator of cell survival in cancer. Here, we report that combined down-regulation of growth arrest- and DNA-damage-inducible proteins (GADD)45α and γ expression by NF-κB is an essential step for various cancer types to escape programmed cell death. We demonstrate that inhibition of NF-κB in cancer cells results in GADD45α- and γ-dependent induction of apoptosis and inhibition of tumor growth. Inhibition of GADD45α and γ in cancer cells by small interfering RNA abrogates apoptosis induction by the inhibitor of NF-κB and blocks c-Jun N-terminal kinase activation, whereas overexpression of GADD45α and γ activates c-Jun N-terminal kinase and induces apoptosis. These results establish an unambiguous role for the GADD45 family as an essential mediator of cell survival in cancer cells with implications for cancer chemotherapy and novel drug discovery.
机译：NF-κB/IκB信号通路是癌症细胞存活的关键调节剂。在这里，我们报告说，NF-κB联合抑制生长停滞和DNA损伤诱导蛋白（GADD）45α和γ的表达下调是各种癌症逃避程序性细胞死亡的重要步骤。我们证明了抑制癌细胞中的NF-κB会导致GADD45α和γ依赖性的细胞凋亡诱导和肿瘤生长抑制。小干扰RNA对癌细胞中GADD45α和γ的抑制作用消除了NF-κB抑制剂诱导的凋亡诱导，并阻断了c-Jun N端激酶的激活，而GADD45α和γ的过表达则激活了c-Jun N端激酶并诱导了凋亡。 。这些结果确立了GADD45家族作为癌细胞中细胞存活的重要介体的明确作用，对癌症化学疗法和新药发现具有影响。

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