title: Molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer.
abstract: OBJECTIVE
  The goal of this study was to establish a common set of molecules that regulate cell invasion in head and neck cancer (HNC).
  
  
  METHODS
  Five invasive sublines derived from HNC cell lines were established using the Matrigel selection method. Proteomic technology, MetaCore algorithm, and reverse transcriptase-PCR methods were used to search for molecules that contribute to the invasion phenotype. Cellular functional analyses and clinical association studies were applied to examine the significance of the molecules.
  
  
  RESULTS
  Fifty-two proteins were identified in more than two of the four independent proteomic experiments, including 10 (19%) molecular chaperones. Seven chaperones were confirmed to be differentially expressed in five sublines, Hsp90α, Hsp90β, Hsp90-B1/Gp96, Hsp70-A5/Grp78, and HYOU1, that upregulate, whereas Hsp60 and glucosidase-α neutral AB (GANAB) downregulate. Four molecules were further investigated. In all cell lines, knockdown of Hsp60 or GANAB and silencing of Gp96 or Grp78 considerably enhanced or reduced cell migration and invasion, respectively. Clinical association studies consistently revealed that low levels of Hsp60 or GANAB and high levels of Gp96 or Grp78 are significantly associated with advanced cancer (P < 0.001 to P = 0.047, respectively, for the four molecules) and poor survival (P < 0.001 to P = 0.025, respectively, for the four molecules).
  
  
  CONCLUSIONS
  Our study defined molecular chaperones as a common set of proteins that regulate the invasion phenotype of HNC. Loss of the tumor suppression function of Hsp60 or GANAB and acquisition of the oncogenic function of Gp96 or Grp78 contribute to aggressive cancers. These molecules may serve as prognostic markers and targets for cancer drug development.
authors.affiliation: Department of Medical Biotechnology, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ching-Chi
authors.initials: CC
authors.lastname: Chiu
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Lee
authors.forename: Yin-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Lu
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Wang
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.forename: Joseph Tung-Chieh
authors.initials: JT
authors.lastname: Chang
authors.forename: Ann-Joy
authors.initials: AJ
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics; D010641:Phenotype; D040901:Proteomics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D018832:Molecular Chaperones