title: The role of ubiquitin-specific protease 14 (USP14) in cell adhesion-mediated drug resistance (CAM-DR) of multiple myeloma cells.
abstract: OBJECTIVE
  Cell adhesion-mediated drug resistance (CAM-DR) is one of the mechanisms underlying the drug resistance in multiple myeloma (MM). Ubiquitin-specific protease 14 (USP14) is downregulated in the apoptotic model and upregulated in the adhesive model of MM. This study was undertaken to determine the role of USP14 in CAM-DR of MM cells.
  
  
  METHODS
  We examined the expression of USP14 in the apoptotic model of MM. The mechanism of USP14 in the process of apoptosis was further explored by flow cytometry assay and co-immunoprecipitation. We then performed the cell co-culture and adhesion assay and cell viability assay to investigate the effect of USP14 on adhesive rate and drug resistance in MM.
  
  
  RESULTS
  We discovered that USP14 played a negative role in cell apoptosis, which is correlated with Bcl-xl. Moreover, overexpression of USP14 in MM cell adhesion model could enhance the ability of cell adhesion by regulating Wnt-signaling pathways, thereby promoting the CAM-DR in MM.
  
  
  CONCLUSIONS
  USP14 participates in CAM-DR of MM through acting as a bridge between Bcl-xl apoptotic pathway and Wnt-signaling pathways and may be represented as a good candidate for pursuing clinical trials in MM.
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Chaoyan
authors.initials: C
authors.lastname: Shen
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Ding
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Yuchan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Song
authors.initials: S
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008942:Mitoxantrone / Q000494:pharmacology; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C509299:USP14 protein, human; D051020:bcl-X Protein; D008942:Mitoxantrone; D043222:Ubiquitin Thiolesterase
keywords: Multiple myeloma; Ubiquitin-specific protease 14; apoptosis; cell adhesion-mediated drug resistance