Document Detail


EGFR through STAT3 modulates ΔN63α expression to sustain tumor-initiating cell proliferation in squamous cell carcinomas.
MedLine Citation:
PMID:  23018838     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many squamous cell carcinomas (SCCs) are characterized by high levels of EGFR and by overexpression of the ΔNp63α isoform. Here, we investigated the regulation of ΔNp63α expression upon EGFR activation and the role of the EGFR-ΔNp63α axis in proliferation of SCC tumor-initiating cells (TICs). SCC cell lines A-431, Cal-27, and SCC-25 treated with EGF showed a time-dependent increase in ΔNp63α expression at the protein and mRNA levels, which was blocked by the tyrosine kinase inhibitor (TKI) Lapatinib. RNA interference experiments suggested the role of STAT3 in regulating ΔNp63α expression downstream of EGFR. Inactivation of EGFR by the monoclonal antibody Cetuximab and RNA interference against STAT3 or ΔNp63α impaired the TICs ability to grow under non-differentiating conditions. Radiation treatment, which triggers EGFR activation, induced ΔNp63α accumulation without affecting TICs proliferation, whereas the combination Cetuximab plus radiation significantly reduced TICs growth under non-differentiating conditions. Together, our findings provide evidence that ΔNp63α expression is regulated by EGFR activation through STAT3 and that the EGFR-ΔNp63α axis is crucial for proliferation of TICs present in SCCs.
Authors:
Francesca Ripamonti; Luisa Albano; Anna Rossini; Serena Borrelli; Sonia Fabris; Roberto Mantovani; Antonino Neri; Andrea Balsari; Alessandra Magnifico; Elda Tagliabue
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  228     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-05-22     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  871-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Molecular Targeting Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / pharmacology
Carcinoma, Squamous Cell / genetics,  metabolism*,  pathology*
Cell Differentiation / drug effects,  genetics
Cell Line, Tumor
Cell Proliferation / drug effects
Humans
MCF-7 Cells
Neoplastic Stem Cells / drug effects,  metabolism*,  pathology*
Protein Kinase Inhibitors / pharmacology
Quinazolines / pharmacology
RNA, Messenger / genetics
Receptor, Epidermal Growth Factor / genetics,  metabolism*
STAT3 Transcription Factor / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Protein Kinase Inhibitors; 0/Quinazolines; 0/RNA, Messenger; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0VUA21238F/lapatinib; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; PQX0D8J21J/cetuximab

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


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