title: The overexpression of 14-3-3ζ and Hsp27 promotes non–small cell lung cancer progression.
abstract: BACKGROUND
  The 14-3-3ζ protein has been identified as a putative oncoprotein in several cancers, including non–small cell lung cancer (NSCLC). However, the mechanisms underlying its functions have not been well defined.
  
  
  METHODS
  Proteins that interact with 14-3-3ζ were identified through coimmunoprecipitation and mass spectrometry in NSCLC cells. The interaction of 14-3-3ζ with these molecular partners and their roles in the invasiveness and metastasis of NSCLC cells were assayed through specific disruptions in the 14-3-3ζ signaling network. In addition, the clinical implications of this 14-3-3ζ complex were examined in samples from patients with NSCLC.
  
  
  RESULTS
  Among the identified proteins that interacted with 14-3-3ζ, there were 230 proteins in 95-D cells, 181 proteins in 95-C cells, and 203 proteins in A549 cells; and 16 interacting proteins were identified that overlapped between all cell lines. Further studies revealed 14-3-3ζ complexes within the heat shock protein 27 (Hsp27) protein and demonstrated that the interference of Hsp27 or 14-3-3ζ inhibited the invasion and metastasis of NSCLC cells. The invasive and metastatic capabilities of cells with both Hsp27 and 14-3-3ζ interference could be completely restored only by Hsp27 and 14-3-3ζ complementary DNA transfection and not by either agent alone. Clinically, the postoperative 5-year overall survival (OS) in patients who had high expression of both 14-3-3ζ and Hsp27 was significantly lower than the 5-year OS in patients who had low expression of both 14-3-3ζ and Hsp27 (26.5% vs 59.7%, respectively). Multivariate analysis revealed that the combined expression of 14-3-3ζ and Hsp27 was an independent prognostic indicator of OS(P = .036).
  
  
  CONCLUSIONS
  The current data suggest that the combined expression of 14-3-3ζ and Hsp27 may be a biomarker for predicting survival in patients with NSCLC, and this combination may have potential as a therapeutic target for NSCLC.
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Zhao
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Ding
authors.forename: Chun-Lai
authors.initials: CL
authors.lastname: Lu
authors.forename: Zong-Wu
authors.initials: ZW
authors.lastname: Lin
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000328:Adult; D000595:Amino Acid Sequence; D000704:Analysis of Variance; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D047468:Immunoprecipitation; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D048948:14-3-3 Proteins; D015820:Cadherins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C572235:YWHAZ protein, human