title: Glucose-regulated protein 58 modulates β-catenin protein stability in a cervical adenocarcinoma cell line.
abstract: BACKGROUND
  Cervical cancer continues to threaten women's health worldwide, and the incidence of cervical adenocarcinoma (AD) is rising in the developed countries. Previously, we showed that glucose-regulated protein 58 (Grp58) served as an independent factor predictive of poor prognosis of patients with cervical AD. However, the molecular mechanism underlying the involvement of Grp58 in cervical carcinogenesis is currently unknown.
  
  
  METHODS
  DNA microarray and enrichment analysis were used to identify the pathways disrupted by knockdown of Grp58 expression.
  
  
  RESULTS
  Among the pathway identified, the WNT signaling pathway was one of those that were significantly associated with knockdown of Grp58 expression in HeLa cells. Our experiments showed that β-catenin, a critical effector of WNT signaling, was stabilized thereby accumulated in stable Grp58 knockdown cells. Membrane localization of β-catenin was observed in Grp58 knockdown, but not control cells. Using a transwell assay, we found that accumulated β-catenin induced by Grp58 knockdown or lithium chloride treatment inhibited the migration ability of HeLa cells. Furthermore, an inverse expression pattern of Grp58 and β-catenin was observed in cervical tissues.
  
  
  CONCLUSIONS
  Our results demonstrate that β-catenin stability is negatively regulated by Grp58 in HeLa cells. Overexpression of Grp58 may be responsible for the loss of or decrease in membranous β-catenin expression in cervical AD.
authors: Chia-Jung
authors: CJ
authors: Liao
authors: Tzu-I
authors: TI
authors: Wu
authors: Ya-Hui
authors: YH
authors: Huang
authors: Ting-Chang
authors: TC
authors: Chang
authors: Chyong-Huey
authors: CH
authors: Lai
authors: Shih-Ming
authors: SM
authors: Jung
authors: Chuen
authors: C
authors: Hsueh
authors: Department of Biochemistry, Chang-Gung University, 259 Wen-hwa 1 Road, Taoyuan 333, Taiwan. khlin@mail.cgu.edu.tw.
authors: Kwang-Huei
authors: KH
authors: Lin
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D019704:Protein Disulfide-Isomerases / Q000235:genetics* / Q000378:metabolism; D055550:Protein Stability; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human; D018021:Lithium Chloride