Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2007-11-2
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth..., http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein, http://linkedlifedata.com/resource/pubmed/chemical/Smad2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein, http://linkedlifedata.com/resource/pubmed/chemical/Smad3 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/TGF-beta type I receptor, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/endoglin protein, mouse
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10268-77
pubmed:meshHeading
pubmed-meshheading:17974968-Animals, pubmed-meshheading:17974968-Cadherins, pubmed-meshheading:17974968-Cell Movement, pubmed-meshheading:17974968-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:17974968-Keratinocytes, pubmed-meshheading:17974968-Mice, pubmed-meshheading:17974968-Mice, SCID, pubmed-meshheading:17974968-Protein-Serine-Threonine Kinases, pubmed-meshheading:17974968-RNA, Messenger, pubmed-meshheading:17974968-RNA, Small Interfering, pubmed-meshheading:17974968-Receptors, Transforming Growth Factor beta, pubmed-meshheading:17974968-Signal Transduction, pubmed-meshheading:17974968-Skin Neoplasms, pubmed-meshheading:17974968-Smad2 Protein, pubmed-meshheading:17974968-Smad3 Protein, pubmed-meshheading:17974968-Transforming Growth Factor beta1, pubmed-meshheading:17974968-Tumor Suppressor Proteins
pubmed:year
2007
pubmed:articleTitle
A role for endoglin as a suppressor of malignancy during mouse skin carcinogenesis.
pubmed:affiliation
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't