Interplay between unfolded protein response and autophagy promotes tumor drug resistance.
Interplay between unfolded protein response and autophagy promotes tumor drug resistance.
复制标题
未折叠蛋白反应和自噬之间的相互作用促进肿瘤耐药性。
DOI：
10.3892/ol.2015.3508
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发表时间：
2015-10
期刊：
影响因子：
2.9
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Yan MM;Ni JD;Song D;Ding M;Huang J
内质网（ER）通过促进新生蛋白的正确折叠和介导未折叠或错误折叠蛋白的降解，即内质网相关降解，参与分泌蛋白的质量控制。当未折叠或错误折叠的蛋白丰富时，未折叠蛋白反应（UPR）被激发，这是一个从内质网到细胞核的自适应信号级联，恢复内质网的稳态功能。自噬是一种保守的分解代谢过程，细胞中的长寿命蛋白质和受损细胞器被吞噬并降解以维持体内平衡。UPR和自噬同时发生，并参与病理过程，包括肿瘤发生、恶性肿瘤的化疗耐药和神经变性。累积的数据表明，UPR可能诱导自噬，而自噬能够减轻UPR。然而，自噬与UPR相互作用的详细机制尚不完全清楚。本文旨在描述这两个过程的核心途径，并阐明自噬和UPR是如何被调节的。此外，本文还讨论了UPR与自噬串扰的分子机制及其在恶性肿瘤生存和耐药中的作用。
The endoplasmic reticulum (ER) is involved in the quality control of secreted protein via promoting the correct folding of nascent protein and mediating the degradation of unfolded or misfolded protein, namely ER-associated degradation. When the unfolded or misfolded proteins are abundant, the unfolded protein response (UPR) is elicited, an adaptive signaling cascade from the ER to the nucleus, which restores the homeostatic functions of the ER. Autophagy is a conserved catabolic process where cellular long-lived proteins and damaged organelles are engulfed and degraded for recycling to maintain homeostasis. The UPR and autophagy occur simultaneously and are involved in pathological processes, including tumorigenesis, chemoresistance of malignancies and neurodegeneration. Accumulative data has indicated that the UPR may induce autophagy and that autophagy is able to alleviate the UPR. However, the detailed mechanism of interplay between autophagy and UPR remains to be fully understood. The present review aimed to depict the core pathways of the two processes and to elucidate how autophagy and UPR are regulated. Moreover, the review also discusses the molecular mechanism of crosstalk between the UPR and autophagy and their roles in malignant survival and drug resistance.