Document Detail


A role for endoglin as a suppressor of malignancy during mouse skin carcinogenesis.
MedLine Citation:
PMID:  17974968     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endoglin is a membrane glycoprotein that acts as a coreceptor for transforming growth factor-beta. We and others have previously suggested a function of endoglin as a tumor suppressor in epithelial cancer. Here, we study the expression of endoglin during chemical mouse skin carcinogenesis. We find that shedding of membrane endoglin, allowing the secretion of a soluble endoglin form, is a late event associated with progression from squamous to spindle cell carcinomas. Knockdown of endoglin in transformed keratinocytes activates the Smad2/3 signaling pathway resulting in cell growth arrest, delayed tumor latencies, and a squamous to spindle phenotypic conversion. Forced expression of the long endoglin isoform in spindle carcinoma cells blocks transforming growth factor-beta1 stimulation of Smad2/3 signaling and prevents tumor formation. In contrast, expression of the short endoglin isoform has no effect on spindle cell growth in vitro or in vivo. Our results show that endoglin behaves as a suppressor of malignancy during the late stages of carcinogenesis. Therefore, disruption of membrane endoglin emerges as a crucial event for progression to spindle cell carcinomas.
Authors:
Eduardo Pérez-Gómez; María Villa-Morales; Javier Santos; José Fernández-Piqueras; Carlos Gamallo; Javier Dotor; Carmelo Bernabéu; Miguel Quintanilla
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  67     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-02     Completed Date:  2007-11-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10268-77     Citation Subset:  IM    
Affiliation:
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cadherins / genetics
Cell Movement
Intracellular Signaling Peptides and Proteins / genetics,  physiology*
Keratinocytes / pathology
Mice
Mice, SCID
Protein-Serine-Threonine Kinases / genetics
RNA, Messenger / analysis
RNA, Small Interfering / genetics
Receptors, Transforming Growth Factor beta / genetics
Signal Transduction
Skin Neoplasms / pathology,  prevention & control*
Smad2 Protein / physiology
Smad3 Protein / physiology
Transforming Growth Factor beta1 / physiology
Tumor Suppressor Proteins / physiology*
Chemical
Reg. No./Substance:
0/Cadherins; 0/Intracellular Signaling Peptides and Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Receptors, Transforming Growth Factor beta; 0/Smad2 Protein; 0/Smad2 protein, mouse; 0/Smad3 Protein; 0/Smad3 protein, mouse; 0/Transforming Growth Factor beta1; 0/Tumor Suppressor Proteins; 0/endoglin protein, mouse; EC 2.7.1.11/TGF-beta type I receptor; EC 2.7.11.1/Protein-Serine-Threonine Kinases

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


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