Autophagy in tumor suppression and cancer therapy.
Autophagy in tumor suppression and cancer therapy.
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DOI：
10.1615/critreveukargeneexpr.v21.i1.50
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发表时间：
2011
影响因子：
1.6
通讯作者：
Murphy M
中科院分区：
文献类型：
--
作者：
Kung CP;Budina A;Balaburski G;Bergenstock MK;Murphy M
自噬是一种应激诱导的细胞存活程序，其中处于代谢、蛋白毒性或其他应激下的细胞通过将功能失调的细胞器和/或错误折叠/多聚泛素化的蛋白质经由称为自噬体的专门结构穿梭到溶酶体进行降解来去除它们。最终的结果是释放游离氨基酸和代谢物用于细胞存活。对于肿瘤细胞来说，自噬是一把双刃剑：自噬基因在人类肿瘤中经常被单等位基因删除、沉默或突变，导致氧化应激增加的环境，这有利于DNA损伤、基因组不稳定和肿瘤进展。因此，自噬是肿瘤抑制性的。相比之下，重要的是要注意，尽管肿瘤细胞具有降低的自噬水平，但它们并没有完全消除这种途径。此外，肿瘤细胞暴露于代谢和其他应激增加的环境中，使它们依赖于基础自噬来生存。因此，自噬抑制是鉴定新型抗癌疗法的积极途径。毫不奇怪，自噬和癌症领域在过去10年中经历了爆炸式的研究。这篇综述涵盖了自噬的基本机制，讨论了其在肿瘤抑制和癌症治疗中的作用，并提出了未来出现的问题。
Autophagy is a stress-induced cell survival program whereby cells under metabolic, proteotoxic, or other stress remove dysfunctional organelles and/or misfolded/polyubiquitylated proteins by shuttling them via specialized structures called autophagosomes to the lysosome for degradation. The end result is the release of free amino acids and metabolites for use in cell survival. For tumor cells, autophagy is a double-edged sword: autophagy genes are frequently mono-allelically deleted, silenced, or mutated in human tumors, resulting in an environment of increased oxidative stress that is conducive to DNA damage, genomic instability, and tumor progression. As such, autophagy is tumor suppressive. In contrast, it is important to note that although tumor cells have reduced levels of autophagy, they do not eliminate this pathway completely. Furthermore, the exposure of tumor cells to an environment of increased metabolic and other stresses renders them reliant on basal autophagy for survival. Therefore, autophagy inhibition is an active avenue for the identification of novel anti-cancer therapies. Not surprisingly, the field of autophagy and cancer has experienced an explosion of research in the past 10 years. This review covers the basic mechanisms of autophagy, discusses its role in tumor suppression and cancer therapy, and posits emerging questions for the future.
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影响因子：
6.2
作者：
Coppola, Domenico;Khalil, Farah;Eschrich, Steven A.;Boulware, David;Yeatman, Timothy;Wang, Hong-Gang
通讯作者：
Wang, Hong-Gang
影响因子：
11.2
作者：
Apel, Anja;Herr, Ingrid;Mayer, Andreas
通讯作者：
Mayer, Andreas
影响因子：
4.8
作者：
Cuddeback, SM;Yamaguchi, H;Wang, HG
通讯作者：
Wang, HG
p62/SQSTM1形成自噬降解的蛋白质聚集体，并对亨廷顿蛋白诱导的细胞死亡具有保护作用。
影响因子：
7.8
作者：
Bjorkoy, Geir;Lamark, Trond;Brech, Andreas;Outzen, Heidi;Perander, Maria;Overvatn, Aud;Stenmark, Harald;Johansen, Terje
通讯作者：
Johansen, Terje
影响因子：
5.3
作者：
Bellot, Gregory;Garcia-Medina, Raquel;Mazure, Nathalie M.
通讯作者：
Mazure, Nathalie M.