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自噬与细胞器在癌症中的平衡。

Autophagy and organelle homeostasis in cancer.

机构信息

Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.

Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.

出版信息

Dev Cell. 2021 Apr 5;56(7):906-918. doi: 10.1016/j.devcel.2021.02.010. Epub 2021 Mar 8.

Abstract

Beginning with the earliest studies of autophagy in cancer, there have been indications that autophagy can both promote and inhibit cancer growth and progression; autophagy regulation of organelle homeostasis is similarly complicated. In this review we discuss pro- and antitumor effects of organelle-targeted autophagy and how this contributes to several hallmarks of cancer, such as evading cell death, genomic instability, and altered metabolism. Typically, the removal of damaged or dysfunctional organelles prevents tumor development but can also aid in proliferation or drug resistance in established tumors. By better understanding how organelle-specific autophagy takes place and can be manipulated, it may be possible to go beyond the brute-force approach of trying to manipulate all autophagy in order to improve therapeutic targeting of this process in cancer.

摘要

从最早的癌症自噬研究开始,就有迹象表明自噬既能促进又能抑制癌症的生长和进展;细胞器稳态的自噬调节同样复杂。在这篇综述中,我们讨论了靶向自噬的细胞器的促癌和抑癌作用,以及这如何导致癌症的几个特征,如逃避细胞死亡、基因组不稳定性和代谢改变。通常,清除受损或功能失调的细胞器可以防止肿瘤的发展,但也可以帮助已建立的肿瘤增殖或耐药。通过更好地了解细胞器特异性自噬是如何发生的以及如何进行操纵,就有可能超越试图操纵所有自噬以改善癌症中这一过程的治疗靶向的粗暴方法。

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