Int J Biol Sci 2015; 11(7):803-812. doi:10.7150/ijbs.11100 This issue

Research Paper

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

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Citation:
Ji Gr, Yu Nc, Xue X, Li Zg. PERK-mediated Autophagy in Osteosarcoma Cells Resists ER Stress-induced Cell Apoptosis. Int J Biol Sci 2015; 11(7):803-812. doi:10.7150/ijbs.11100. Available from https://www.ijbs.com/v11p0803.htm

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Abstract

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.

Keywords: PERK, osteosarcoma, autophagy, ER stress, mTORC1