title: PERK-mediated Autophagy in Osteosarcoma Cells Resists ER Stress-induced Cell Apoptosis.
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.
authors.affiliation: Department of Orthopaedics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Guang-rong
authors.initials: GR
authors.lastname: Ji
authors.affiliation: Department of Orthopaedics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Nai-chun
authors.initials: NC
authors.lastname: Yu
authors.affiliation: Department of Orthopaedics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Orthopaedics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Zong-guang
authors.initials: ZG
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism* / Q000503:physiopathology; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D046912:Multiprotein Complexes; C460640:EIF2AK3 protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D019892:eIF-2 Kinase
keywords: ER stress; PERK; autophagy; mTORC1; osteosarcoma