Molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer

Ching Chi Chiu, Chien Yu Lin, Li Yu Lee, Yin Ju Chen, Ya Ching Lu, Hung Ming Wang, Chun Ta Liao, Joseph Tung Chieh Chang, Ann Joy Cheng

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Purpose: The goal of this study was to establish a common set of molecules that regulate cell invasion in head and neck cancer (HNC). Experimental Design: 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). Conclusion: 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 orGANABand 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.

Original languageEnglish
Pages (from-to)4629-4641
Number of pages13
JournalClinical Cancer Research
Volume17
Issue number14
DOIs
Publication statusPublished - Jul 15 2011
Externally publishedYes

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Molecular Chaperones
Head and Neck Neoplasms
Glucosidases
Phenotype
Proteomics
Neoplasms
Proteins
Cell Line
Reverse Transcriptase Polymerase Chain Reaction
Cell Movement
Research Design
Up-Regulation
Down-Regulation
Technology
Pharmaceutical Preparations
Clinical Studies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer. / Chiu, Ching Chi; Lin, Chien Yu; Lee, Li Yu; Chen, Yin Ju; Lu, Ya Ching; Wang, Hung Ming; Liao, Chun Ta; Chang, Joseph Tung Chieh; Cheng, Ann Joy.

In: Clinical Cancer Research, Vol. 17, No. 14, 15.07.2011, p. 4629-4641.

Research output: Contribution to journalArticle

Chiu, Ching Chi ; Lin, Chien Yu ; Lee, Li Yu ; Chen, Yin Ju ; Lu, Ya Ching ; Wang, Hung Ming ; Liao, Chun Ta ; Chang, Joseph Tung Chieh ; Cheng, Ann Joy. / Molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 14. pp. 4629-4641.
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abstract = "Purpose: The goal of this study was to establish a common set of molecules that regulate cell invasion in head and neck cancer (HNC). Experimental Design: 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). Conclusion: 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 orGANABand 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.",
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AU - Chiu, Ching Chi

AU - Lin, Chien Yu

AU - Lee, Li Yu

AU - Chen, Yin Ju

AU - Lu, Ya Ching

AU - Wang, Hung Ming

AU - Liao, Chun Ta

AU - Chang, Joseph Tung Chieh

AU - Cheng, Ann Joy

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N2 - Purpose: The goal of this study was to establish a common set of molecules that regulate cell invasion in head and neck cancer (HNC). Experimental Design: 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). Conclusion: 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 orGANABand 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.

AB - Purpose: The goal of this study was to establish a common set of molecules that regulate cell invasion in head and neck cancer (HNC). Experimental Design: 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). Conclusion: 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 orGANABand 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.

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