International Journal Of Bilogical Sciences
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PERK-mediated Autophagy in Osteosarcoma Cells Resists ER Stress-induced Cell Apoptosis
Guang-rong Ji, Nai-chun Yu, Xiang Xue, Zong-guang Li
Department of Orthopaedics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China Corresponding author: Prof. Guang-rong Ji, Department of Orthopaedics, The 2nd Affiliated Hospital of Harbin Medical University, No. 246, Rd Xuefu, District Nangang, Harbin, 150001, China. Tel: +86-451-8660-5152; Fax: +86-451-8660-5152; Email: email@example.com or Jiguangrong08@163.com.
Osteosarcoma is a bone cancer that develops commonly in children and adolescents. However, osteosarcoma treatments often fail by the development of chemoresistance to apoptosis, and the molecular mechanisms remain unclear. In this study, we propose that autophagy is responsible for osteosarcomatous resistance to apoptosis. We implicate PERK-mediated autophagy as a significant contributor to apoptosis resistance due to ER stress in osteosarcoma cells. By immunostainings and western blots, we identified that PERK activated osteosarcomatous autophagy via inhibiting mTORC1 pathway, thereby preventing cell apoptosis. While using RNAi, we knocked down PERK and found that autophagy was suppressed, result in osteosarcomatous apoptosis. Our results identify a novel role of PERK-mediated autophagy as a significant mechanism for osteosarcoma cell survival. These results will help to understand the mechanism of chemoresistance in osteosarcoma cells, and indicate a novel target for improving osteosarcoma therapy.
PERK, osteosarcoma, autophagy, ER stress, mTORC1
Date Deposited : 25 Feb 2016 11:27
Official URL: http://www.ijbs.com/v11i7
Last Modified : 25 Feb 2016 11:27
Volume 11, Number 7, - 2015 , ISSN 1449-2288
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