GRP78 inhibition enhances ATF4-induced cell death by the deubiquitination and stabilization of CHOP in human osteosarcoma

• Published in: Cancer letters Vol. 410; pp. 112 - 123
• Main Authors: Luo, Jie, Xia, Yuanzheng, Luo, Jun, Li, Junhe, Zhang, Chao, Zhang, Hao, Ma, Ting, Yang, Lei, Kong, Lingyi
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.12.2017; Elsevier Limited
• Subjects: Activating Transcription Factor 4 - genetics; Activating Transcription Factor 4 - metabolism; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; ATF4; Bone cancer; Bone Neoplasms - drug therapy; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Bortezomib; Bortezomib - pharmacology; Cancer therapies; Cell death; Cell Death - drug effects; Cell Line, Tumor; Chemotherapy; CHOP; CHOP protein; Dose-Response Relationship, Drug; E1A-Associated p300 Protein - metabolism; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; Event-related potentials; Gene Expression Regulation, Neoplastic; GRP78; Heat-Shock Proteins - antagonists & inhibitors; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Humans; Immunoglobulins; Laboratory animals; Male; Mice, Nude; Osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma - genetics; Osteosarcoma - metabolism; Osteosarcoma - pathology; Plasmids; Polyacetylenes - pharmacology; Protein Binding; Protein biosynthesis; Protein Interaction Domains and Motifs; Protein Stability; Proteins; RNA Interference; Sarcoma; Signal transduction; Signal Transduction - drug effects; Time Factors; Transcription Factor CHOP - genetics; Transcription Factor CHOP - metabolism; Transfection; Tumorigenesis; Tumors; Ubiquitination; Xenograft Model Antitumor Assays; Xenografts; China; CFDA SE; HSPA5; OS; GRP78; BTZ; PERK; ER; Ubiquitination; CHX; Tg; Osteosarcoma; DDIT3; UPR; EdU; IRE1; ROS; CHOP; ATF4

New targeted therapies are urgently needed to improve the survival of patients with refractory osteosarcoma (OS). In this study, we show that bortezomib (BTZ), not for OS treatment in the clinic, induces endoplasmic reticulum (ER) stress in U-2 OS cells. Loss of GRP78 sensitizes OS to BTZ with conco...