p62/SQSTM1 involved in cisplatin resistance in human ovarian cancer cells by clearing ubiquitinated proteins

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• 作者：Huimei Yu^a ; ^c ; Jing Su^a ; ^c ; Ye Xu^a ; ^b ; Jinsong Kang^a ; Hongyan Li^a ; Ling Zhang^a ; Haowei Yi^a ; Xiyan Xiang^a ; Fei Liu^a ; Liankun Sun^a ; ^{sunlk@jlu.edu.cn"" rel=""nofollow}
• 关键词：p62/SQSTM1 ; Ubiquitinated proteins ; Apoptosis ; Cisplatin ; Drug resistance ; Ovarian cancer
• 刊名：European Journal of Cancer
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：47
• 期：10
• 页码：1585-1594
• 全文大小：1170 K

文摘

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.