title: Nogo-B receptor promotes the chemoresistance of human hepatocellular carcinoma via the ubiquitination of p53 protein.
abstract: Nogo-B receptor (NgBR), a type I single transmembrane domain receptor is the specific receptor for Nogo-B. Our previous work demonstrated that NgBR is highly expressed in breast cancer cells, where it promotes epithelial mesenchymal transition (EMT), an important step in metastasis. Here, we show that both in vitro and in vivo increased expression of NgBR contributes to the increased chemoresistance of Bel7402/5FU cells, a stable 5-FU (5-Fluorouracil) resistant cell line related Bel7402 cells. NgBR knockdown abrogates S-phase arrest in Bel7402/5FU cells, which correlates with a reduction in G1/S phase checkpoint proteins p53 and p21. In addition, NgBR suppresses p53 protein levels through activation of the PI3K/Akt/MDM2 pathway, which promotes p53 degradation via the ubiquitin proteasome pathway and thus increases the resistance of human hepatocellular cancer cells to 5-FU. Furthermore, we found that NgBR expression is associated with a poor prognosis of human hepatocellular carcinoma (HCC) patients. These results suggest that targeting NgBR in combination with chemotherapeutic drugs, such as 5-FU, could improve the efficacy of current anticancer treatments.
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiiated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Chengyong
authors: C
authors: Dong
authors: Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.|Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Division of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Baofeng
authors: B
authors: Zhao
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiiated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Fei
authors: F
authors: Long
authors: Department of Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China.|Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Ying
authors: Y
authors: Liu
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiiated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Zhenzhen
authors: Z
authors: Liu
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiiated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Song
authors: S
authors: Li
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiiated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Xuejun
authors: X
authors: Yang
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiiated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Deguang
authors: D
authors: Sun
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiiated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Haibo
authors: H
authors: Wang
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiiated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Qinlong
authors: Q
authors: Liu
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiiated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Rui
authors: R
authors: Liang
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Yan
authors: Y
authors: Li
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiiated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Zhenming
authors: Z
authors: Gao
authors: Key Laboratory of Proteomics, Dalian Medical University, Dalian, China.
authors: Shujuan
authors: S
authors: Shao
authors: Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Division of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.
authors: Qing Robert
authors: QR
authors: Miao
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiiated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Liming
authors: L
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination; D023041:Xenograft Model Antitumor Assays
chemical_list: C512614:NUS1 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005472:Fluorouracil
keywords: HCC; NgBR; chemoresistance