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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling

Authors: Meng-Ju Wu, Chia-Ing Jan, Yeou-Guang Tsay, Yau-Hua Yu, Chih-Yang Huang, Shu-Chun Lin, Chung-Ji Liu, Yu-Syuan Chen, Jeng-Fan Lo, Cheng-Chia Yu

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) is a highly lethal cancer that contains cellular and functional heterogeneity. Previously, we enriched a subpopulation of highly tumorigenic head and neck cancer initiating cells (HN-CICs) from HNSCC. However, the molecular mechanisms by which to govern the characteristics of HN-CICs remain unclear. GRP78, a stress-inducible endoplasmic reticulum chaperone, has been reported to play a crucial role in the maintenance of embryonic stem cells, but the role of GRP78 in CICs has not been elucidated.

Results

Initially, we recognized GRP78 as a putative candidate on mediating the stemness and tumorigenic properties of HN-CICs by differential systemic analyses. Subsequently, cells with GRP78 anchored at the plasma membrane (memGRP78+) exerted cancer stemness properties of self-renewal, differentiation and radioresistance. Of note, xenotransplantation assay indicated merely 100 memGRP78+ HNSCCs resulted in tumor growth. Moreover, knockdown of GRP78 significantly reduced the self-renewal ability, side population cells and expression of stemness genes, but inversely promoted cell differentiation and apoptosis in HN-CICs. Targeting GRP78 also lessened tumorigenicity of HN-CICs both in vitro and in vivo. Clinically, co-expression of GRP78 and Nanog predicted the worse survival prognosis of HNSCC patients by immunohistochemical analyses. Finally, depletion of GRP78 in HN-CICs induced the expression of Bax, Caspase 3, and PTEN.

Conclusions

In summary, memGRP78 should be a novel surface marker for isolation of HN-CICs, and targeting GRP78 signaling might be a potential therapeutic strategy for HNSCC through eliminating HN-CICs.
Appendix
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Metadata
Title
Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling
Authors
Meng-Ju Wu
Chia-Ing Jan
Yeou-Guang Tsay
Yau-Hua Yu
Chih-Yang Huang
Shu-Chun Lin
Chung-Ji Liu
Yu-Syuan Chen
Jeng-Fan Lo
Cheng-Chia Yu
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-283

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