Document Detail


Cancer stem-like cell properties are regulated by EGFR/AKT/β-catenin signaling and preferentially inhibited by gefitinib in nasopharyngeal carcinoma.
MedLine Citation:
PMID:  23461856     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We report that the epidermal growth factor receptor (EGFR) pathway plays a critical role in regulating cancer stem-like cells (CSCs) in nasopharyngeal carcinoma (NPC), one of the most common malignant tumors in Southeast Asia. Effects of EGFR on maintaining CSCs are mainly mediated by AKT signaling, and β-catenin is responsible for governing CSC properties in response to EGFR/AKT activation. Significantly, CSCs are enriched by cisplatin and decreased by gefitinib in NPC xenograft models. Upon reimplantation in secondary mice, tumor cells derived from cisplatin-treated mice grew rapidly, whereas regrowth of tumor cells from gefitinib-treated mice was severely diminished. We further demonstrate that expression of EGFR correlates with expression of β-catenin and Nanog in primary tumor specimens from NPC patients. These findings provide mechanistic and preclinical evidence supporting the use of gefitinib alone or in combination with a chemotherapeutic agent in first-line therapy for patients with NPC. In addition, our results suggest that targeting β-catenin represents a rational clinical modality for patients whose tumors harbor activated EGFR or AKT.
Authors:
Lei Ma; Gong Zhang; Xiao-Bo Miao; Xu-Bin Deng; Yue Wu; Ying Liu; Zhi-Ru Jin; Xi-Qing Li; Qiu-Zhen Liu; Du-Xin Sun; Joseph R Testa; Kai-Tai Yao; Guang-Hui Xiao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-04-08
Journal Detail:
Title:  The FEBS journal     Volume:  280     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-25     Completed Date:  2013-06-18     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2027-41     Citation Subset:  IM    
Copyright Information:
© 2013 The Authors Journal compilation © 2013 FEBS.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*
Carcinoma / drug therapy,  metabolism,  pathology*
Cell Line, Tumor
Cell Proliferation
Cell Survival / drug effects
Cell Transformation, Neoplastic / metabolism
Cisplatin / pharmacology
Gene Knockdown Techniques
Homeodomain Proteins / metabolism
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Nasopharyngeal Neoplasms / drug therapy,  metabolism,  pathology*
Neoplasm Transplantation
Neoplastic Stem Cells / drug effects,  metabolism*
Proto-Oncogene Proteins c-akt / metabolism
Quinazolines / pharmacology*
Receptor, Epidermal Growth Factor / antagonists & inhibitors,  genetics,  metabolism*
Side-Population Cells / drug effects,  metabolism
Signal Transduction*
Spheroids, Cellular / metabolism,  physiology
Xenograft Model Antitumor Assays
beta Catenin / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
CA77429/CA/NCI NIH HHS; R01 CA077429/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Homeodomain Proteins; 0/NANOG protein, human; 0/Quinazolines; 0/beta Catenin; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; Q20Q21Q62J/Cisplatin; S65743JHBS/gefitinib
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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