title: Mutual regulation between Raf/MEK/ERK signaling and Y-box-binding protein-1 promotes prostate cancer progression.
abstract: OBJECTIVE
  Y-box-binding protein-1 (YB-1) is known to conduct various functions related to cell proliferation, anti-apoptosis, epithelial-mesenchymal transition, and castration resistance in prostate cancer. However, it is still unknown how YB-1 affects cancer biology, especially its correlations with the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, we aimed to examine the interaction between YB-1 and the MAPK pathway in prostate cancer.
  
  
  METHODS
  Quantitative real-time PCR, Western blotting, and co-immunoprecipitation assay were conducted in prostate cancer cells. YB-1, phosphorylated YB-1 (p-YB-1), and ERK2 protein expressions in 165 clinical specimens of prostate cancer were investigated by immunohistochemistry. YB-1, p-YB-1, and ERK2 nuclear expressions were compared with clinicopathologic characteristics and patient prognoses.
  
  
  RESULTS
  EGF upregulated p-YB-1, whereas MEK inhibitor (U0126, PD98059) decreased p-YB-1. Inversely, silencing of YB-1 using siRNA decreased the expression of ERK2 and phosphorylated MEK, ERK1/2, and RSK. Furthermore, YB-1 interacted with ERK2 and Raf-1 and regulated their expressions, through the proteasomal pathway. Immunohistochemical staining showed a significant correlation among the nuclear expressions of YB-1, p-YB-1, and ERK2. The Cox proportional hazards model revealed that high ERK2 expression was an independent prognostic factor [HR, 7.947; 95% confidence interval (CI), 3.527-20.508; P<0.0001].
  
  
  CONCLUSIONS
  We revealed the functional relationship between YB-1 and MAPK signaling and its biochemical relevance to the progression of prostate cancer. In addition, ERK2 expression was an independent prognostic factor. These findings suggest that both the ERK pathway and YB-1 may be promising molecular targets for prostate cancer diagnosis and therapeutics.
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Imada
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kohashi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kuroiwa
authors.forename: YooHyun
authors.initials: Y
authors.lastname: Song
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
mesh_terms: D063646:Carcinogenesis; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D051840:Y-Box-Binding Protein 1 / Q000235:genetics* / Q000378:metabolism; D048490:raf Kinases / Q000235:genetics*
chemical_list: D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D048490:raf Kinases