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

研究成果: 雜誌貢獻文章

42 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)4629-4641
頁數13
期刊Clinical Cancer Research
17
發行號14
DOIs
出版狀態已發佈 - 七月 15 2011
對外發佈Yes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Chiu, C. C., Lin, C. Y., Lee, L. Y., Chen, Y. J., Lu, Y. C., Wang, H. M., Liao, C. T., Chang, J. T. C., & Cheng, A. J. (2011). Molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer. Clinical Cancer Research, 17(14), 4629-4641. https://doi.org/10.1158/1078-0432.CCR-10-2107