Linked Life Data

16847455

Source:http://linkedlifedata.com/resource/pubmed/id/16847455

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-1-19
pubmed:abstractText
Leucine-rich repeats and immunoglobulin-like domains-1 (LRIG1) is a transmembrane protein with an ectodomain containing 15 leucine-rich repeats (LRRs) homologous to mammalian decorin and the Drosophila kekkon1 gene. In this study, we demonstrate that a soluble ectodomain of LRIG1, containing only the LRRs, inhibits ligand-independent epidermal growth factor receptor (EGFR) activation and causes growth inhibition of A431, HeLa and MDA-468 carcinoma cells. In contrast, cells that do not express detectable levels of EGFR fail to respond to soluble LRIG1. However, when a functional EGFR gene is introduced in these cells, they become growth-inhibited by soluble LRIG1 protein. Furthermore, we demonstrate the existence of high-affinity (K(d)=10 nM) binding sites on the A431 cells that can be competitively displaced (up to 75%) by molar excess of EGF. Even more powerful effects are obtained with a chimeric proteoglycan harboring the N-terminus of decorin, substituted with a single glycosaminoglycan chain, fused to the LRIG1 ectodomain. Both proteins also inhibit ligand-dependent activation of the EGFR and extracellular signal-regulated protein kinase 1/2 signaling in a rapid and dose-dependent manner. These results suggest a novel mechanism of action evoked by a soluble ectodomain of LRIG1 protein that could modulate EGFR signaling and its growth-promoting activity. Attenuation of EGFR activity without physical downregulation of the receptor could represent a novel therapeutic approach toward malignancies in which EGFR plays a primary role in tumor growth and survival.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
368-81
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16847455-Amino Acid Sequence, pubmed-meshheading:16847455-Animals, pubmed-meshheading:16847455-Binding Sites, pubmed-meshheading:16847455-CHO Cells, pubmed-meshheading:16847455-Cell Proliferation, pubmed-meshheading:16847455-Cricetinae, pubmed-meshheading:16847455-Cricetulus, pubmed-meshheading:16847455-Decorin, pubmed-meshheading:16847455-Extracellular Matrix Proteins, pubmed-meshheading:16847455-Gene Expression Regulation, pubmed-meshheading:16847455-Genes, Dominant, pubmed-meshheading:16847455-HeLa Cells, pubmed-meshheading:16847455-Humans, pubmed-meshheading:16847455-Ligands, pubmed-meshheading:16847455-Membrane Glycoproteins, pubmed-meshheading:16847455-Molecular Sequence Data, pubmed-meshheading:16847455-Protein Binding, pubmed-meshheading:16847455-Proteoglycans, pubmed-meshheading:16847455-Receptor, Epidermal Growth Factor, pubmed-meshheading:16847455-Recombinant Proteins, pubmed-meshheading:16847455-Sequence Homology, Amino Acid, pubmed-meshheading:16847455-Signal Transduction, pubmed-meshheading:16847455-Tumor Cells, Cultured
pubmed:year
2007
pubmed:articleTitle
A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity.
pubmed:affiliation
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural