Document Detail


Epithelial-mesenchymal transition transcription factor ZEB1/ZEB2 co-expression predicts poor prognosis and maintains tumor-initiating properties in head and neck cancer.
MedLine Citation:
PMID:  22892238     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Both epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties may be involved in metastasis, which contributes to the high mortality rate of patients with head and neck cancers (HNCs). However, the mechanisms through which the EMT transcription factors ZEB1 and ZEB2 regulate HNC are still unclear.
METHODS: Tumor initiating capability of HNC-CH133(+) cells with ZEB1/2 knockdown or co-overexpression was presented in vitro and in vivo.
RESULTS: In the present study, we demonstrated that ZEB1/ZEB2 expression was significantly increased in HNC-CD133(+) CSC-like cells compared with HNC-CD133(-) cells. The small interfering RNA (siRNA)-mediated co-knockdown of ZEB1 and ZEB2 (siZEB1/2) in HNC-CH133(+) cells suppressed their CSC-like properties, including self-renewal ability, the expression of stemness markers, and drug resistance. In contrast, the co-overexpression of ZEB1/ZEB2 in HNC-CD133(-) cells enhanced their sphere-forming ability and increased the percentage of CD44-positive cells and side population cells. In vivo studies showed that the delivery of siZEB1/2 to xenograft tumors in nude mice reduced tumor growth and the rate of distant metastasis. In clinical samples, the levels of ZEB1/ZEB2 expression were low in local lesions but high in metastatic lymph nodes in HNC tissues. Patients with tumors that co-expressed ZEB1(high) and ZEB2(high) had especially poor survival rates.
CONCLUSION: Therapies targeting ZEB1/ZEB2 in HNC-CD133(+) cells may provide a new approach for HNC therapy in the future.
Authors:
Pen-Yuan Chu; Fang-Wei Hu; Cheng-Chia Yu; Lo-Lin Tsai; Chuan-Hang Yu; Buor-Chang Wu; Yi-Wei Chen; Pin-I Huang; Wen-Liang Lo
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-11
Journal Detail:
Title:  Oral oncology     Volume:  49     ISSN:  1879-0593     ISO Abbreviation:  Oral Oncol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-24     Completed Date:  2013-05-30     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  9709118     Medline TA:  Oral Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  34-41     Citation Subset:  IM    
Copyright Information:
Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD / genetics
Antigens, CD44 / analysis
Cell Culture Techniques
Cell Line, Tumor
Cell Proliferation
Cell Survival / genetics
Cell Transformation, Neoplastic / genetics*
Drug Resistance, Neoplasm / genetics
Epithelial-Mesenchymal Transition / genetics*
Female
Gene Knockdown Techniques
Gene Silencing
Glycoproteins / genetics
Head and Neck Neoplasms / genetics*
Homeodomain Proteins / genetics*
Humans
Kruppel-Like Transcription Factors / genetics*
Lymph Nodes / pathology
Lymphatic Metastasis / genetics
Male
Mice
Mice, Nude
Middle Aged
Neoplastic Stem Cells / pathology
Peptides / genetics
Prognosis
RNA, Small Interfering / genetics
Repressor Proteins / genetics*
Transcription Factors / genetics*
Zinc Fingers / genetics*
Chemical
Reg. No./Substance:
0/AC133 antigen; 0/Antigens, CD; 0/Antigens, CD44; 0/Cd44 protein, mouse; 0/Glycoproteins; 0/Homeodomain Proteins; 0/Kruppel-Like Transcription Factors; 0/Peptides; 0/RNA, Small Interfering; 0/Repressor Proteins; 0/Transcription Factors; 0/ZEB1 protein, human; 0/ZEB1 protein, mouse; 0/ZEB2 protein, human; 0/Zfhx1b protein, mouse

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


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