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

Abstract 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...

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Bibliographic Details
Published in:European journal of cancer (1990) 2011-07, Vol.47 (10), p.1585-1594
Main Authors: Yu, Huimei, Su, Jing, Xu, Ye, Kang, Jinsong, Li, Hongyan, Zhang, Ling, Yi, Haowei, Xiang, Xiyan, Liu, Fei, Sun, Liankun
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Apoptosis
Autophagy
Biological and medical sciences
Cell Survival
Cisplatin
Cisplatin - pharmacology
Drug resistance
Drug Resistance, Neoplasm
Endoplasmic Reticulum - metabolism
Female
Gene Expression Regulation, Neoplastic
Hematology, Oncology and Palliative Medicine
Humans
Medical sciences
Microscopy, Confocal - methods
Microscopy, Fluorescence - methods
Ovarian cancer
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - metabolism
p62/SQSTM1
Pharmacology. Drug treatments
Sequestosome-1 Protein
Tumors
Ubiquitin - metabolism
Ubiquitinated proteins
Ubiquitinated Proteins - chemistry
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Summary:Abstract 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.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2011.01.019