p62/SQSTM1 involved in cisplatin resistance in human ovarian cancer cells by clearing ubiquitinated proteins
p62/SQSTM1 involved in cisplatin resistance in human ovarian cancer cells by clearing ubiquitinated proteins
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p62/SQSTM1通过清除泛素化蛋白参与人卵巢癌细胞的顺铂耐药性
DOI：
10.1016/j.ejca.2011.01.019
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发表时间：
2011-07-01
影响因子：
8.4
通讯作者：
Sun, Liankun
中科院分区：
文献类型：
--
作者：
Yu, Huimei;Su, Jing;Sun, Liankun
癌细胞中顺铂耐药的机制尚未完全了解。在这里，我们展示了泛素结合蛋白p62/SQSTM 1在人卵巢癌细胞（HOCC）顺铂耐药中的关键作用。具体来说，我们发现顺铂耐药SKOV 3/DDP细胞表达的p62水平比顺铂敏感SKOV 3细胞高得多。蛋白p62结合泛素化蛋白，用于转运至自噬降解，从而减少SKOV 3/DDP细胞中由内质网（ER）应激诱导的凋亡。敲低p62或使用3-甲基腺嘌呤抑制自噬使SKOV 3/DDP细胞对顺铂重新敏感。总的来说，我们的数据表明，p62作为一个受体或适配器的泛素化蛋白的自噬降解，并在防止ER应激诱导的细胞凋亡，导致顺铂耐药的HOCC中发挥重要作用。(C)2011爱思唯尔有限公司保留所有权利。
Mechanisms of cisplatin resistance in cancer cells are not fully understood. Here, we show a critical role for the ubiquitin-binding protein p62/SQSTM1 in cisplatin resistance in human ovarian cancer cells (HOCCs). Specifically, we found that cisplatin-resistant SKOV3/DDP cells express much higher levels of p62 than do cisplatin-sensitive SKOV3 cells. The protein p62 binds ubiquitinated proteins for transport to autophagic degradation, reducing apoptosis induced by endoplasmic reticulum (ER) stress in SKOV3/DDP cells. Knockdown of p62 or inhibition of autophagy using 3-methyladenine resensitises SKOV3/DDP cells to cisplatin. Collectively, our data indicate that p62 acts as a receptor or adaptor for autophagic degradation of ubiquitinated proteins, and plays an important role in preventing ER stress-induced apoptosis, leading to cisplatin resistance in HOCCs. (C) 2011 Elsevier Ltd. All rights reserved.