Glucose-regulated protein 78 regulates multiple malignant phenotypes in head and neck cancer and may serve as a molecular target of therapeutic intervention

Ching Chi Chiu, Chien Yu Lin, Li Yu Lee, Yin Ju Chen, Ting Fang Kuo, Joseph Tung Chieh Chang, Chun Ta Liao, Hung Ming Wang, Tzu Chen Yen, Chia Rui Shen, Shuen Kuei Liao, Ann Joy Cheng

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46 Citations (Scopus)

Abstract

Glucose-regulated protein 78 (Grp78) is an endoplasmic reticulum chaperone protein and is overexpressed in various cancers. However, it is unclear how significance of this molecule play an active role contributing to the oncogenic effect of head and neck cancer (HNC). To investigate the potential function of Grp78, six HNC cell lines were used. We found that Grp78 is highly expressed in all six cell lines and many of the proteins were localized in the periphery regions, implying other function of this molecule aside from endoplasmic reticulum stress response. Knockdown of Grp78 by small interfering RNA significantly reduced cell growth and colony formation to 53% to 12% compared with that of controls in all six HNC cell lines. Using in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 23% to 2% in all these cell lines tested. In vivo xenograft studies showed that administration of Grp78-small interfering RNA plasmid into HNC xenografts significantly inhibited both tumor growth in situ (>60% inhibition at day 34) and liver metastasis (>90% inhibition at day 20). Our study showed that Grp78 actively regulates multiple malignant phenotypes, including cell growth, migration, and invasion. Because knockdown Grp78 expression succeeds in the reduction of tumor growth and metastatic potential, this molecule may serve as a molecular target of therapeutic intervention for HNC.

Original languageEnglish
Pages (from-to)2788-2797
Number of pages10
JournalMolecular Cancer Therapeutics
Volume7
Issue number9
DOIs
Publication statusPublished - 2008
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Chiu, C. C., Lin, C. Y., Lee, L. Y., Chen, Y. J., Kuo, T. F., Chang, J. T. C., Liao, C. T., Wang, H. M., Yen, T. C., Shen, C. R., Liao, S. K., & Cheng, A. J. (2008). Glucose-regulated protein 78 regulates multiple malignant phenotypes in head and neck cancer and may serve as a molecular target of therapeutic intervention. Molecular Cancer Therapeutics, 7(9), 2788-2797. https://doi.org/10.1158/1535-7163.MCT-08-0172