title: [Expression of SOCS3 and Pyk2 and their correlation in non-small cell lung cancer].
abstract: OBJECTIVE
  To investigate the expression of SOCS3 and Pyk2 and their correlations in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  The expression of SOCS3 and Pyk2 was detected in 100 cases of NSCLC, human bronchial epithelial cells (HBE) and 6 lung cancer cell lines by immunohistochemistry and immunofluorescence staining. The methylation status of SOCS3 was investigated in A549 cells by methylation-specific PCR. A549 cells were either treated with a demethylation agent 5-aza-2'-deoxycytidine (5-aza) or transfected with three SOCS3 mutants with various functional domains deleted. Besides, the cells were pretreated with a proteasome inhibitor β-lactacystin where indicated. The effects of SOCS3 on Pyk2 expression, Pyk2 Tyr 402 and ERK1/2 phosphorylations were assessed by Western blot. RT-PCR was used to estimate Pyk2 mRNA levels. Transwell experiments were performed to evaluate cell migration.
  
  
  RESULTS
  SOCS3 (43.0%, 43/100) and Pyk2 (65.0%, 65/100) were expressed in NSCLC. A significant negative correlation was found between SOCS3 and Pyk2 in both NSCLC tissues and cell lines. SOCS3 was aberrantly methylated and 5-aza restored SOCS3 expression. Transfection studies indicated that exogenous SOCS3 interacted with Pyk2, and both Src homology 2 (SH2) and kinase inhibitory region (KIR) domains contributed to Pyk2 binding. Furthermore, SOCS3 was found to inhibit Pyk2-associated ERK1/2 activity in A549 cells. SOCS3 possibly promoted degradation of Pyk2 in a SOCS-box-dependent manner and interfered with cell migration.
  
  
  CONCLUSIONS
  The data indicates that SOCS3 definitely plays roles in regulating Pyk2 signaling, and cell motility. Decreased SOCS3 induced by methylation may confer a migration advantage to A549 cells.
authors.affiliation: Department of Pathology, the First Affiliated Hospital and College of Basic Sciences, China Medical University, Shenyang 110001, China.
authors.forename: Si-yang
authors.initials: SY
authors.lastname: Zhang
authors.forename: Xue-shan
authors.initials: XS
authors.lastname: Qiu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D019175:DNA Methylation; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D009154:Mutation; D010766:Phosphorylation; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051418:Focal Adhesion Kinase 2