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促进生存的自噬:通过维持癌症特征促进肿瘤进展的新兴候选者。

Pro-survival autophagy: An emerging candidate of tumor progression through maintaining hallmarks of cancer.

机构信息

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India.

出版信息

Semin Cancer Biol. 2020 Nov;66:59-74. doi: 10.1016/j.semcancer.2019.08.020. Epub 2019 Aug 17.

Abstract

Autophagy is an evolutionary conserved catabolic process that regulates the cellular homeostasis by targeting damaged cellular contents and organelles for lysosomal degradation and sustains genomic integrity, cellular metabolism, and cell survival during diverse stress and adverse conditions. Recently, the role of autophagy is extremely debated in the regulation of cancer initiation and progression. Although autophagy has a dichotomous role in the regulation of cancer, growing numbers of studies largely indicate the pro-survival role of autophagy in cancer progression and metastasis. In this review, we discuss the detailed mechanisms of autophagy, the role of pro-survival autophagy that positively drives several classical as well as emerging hallmarks of cancer for tumorigenic progression, and also we address various autophagy inhibitors that could be harnessed against pro-survival autophagy for effective cancer therapeutics. Finally, we highlight some outstanding problems that need to be deciphered extensively in the future to unravel the role of autophagy in tumor progression.

摘要

自噬是一种进化上保守的分解代谢过程,通过靶向溶酶体降解受损的细胞内容物和细胞器来调节细胞内稳态,在各种应激和不利条件下维持基因组完整性、细胞代谢和细胞存活。最近,自噬在癌症发生和发展中的调节作用引起了极大的争议。尽管自噬在调节癌症方面具有双重作用,但越来越多的研究表明,自噬在癌症进展和转移中具有促生存作用。在这篇综述中,我们讨论了自噬的详细机制、促生存自噬的作用,该作用正向驱动几种经典和新兴的癌症特征,促进肿瘤发生进展,并且还讨论了多种自噬抑制剂,这些抑制剂可以被利用来对抗促生存自噬,从而实现有效的癌症治疗。最后,我们强调了一些突出的问题,这些问题需要在未来进行广泛的研究,以揭示自噬在肿瘤进展中的作用。

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