Linked Life Data

21222362

Source:http://linkedlifedata.com/resource/pubmed/id/21222362

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-1-12
pubmed:abstractText
Increased signaling from Met, the receptor for Hepatocyte Growth Factor, promotes pancreatic tumorigenesis and poor patient prognosis by enhancing tumor cell growth, survival and motility. Increased Met levels can result from gene amplification or increased transcription. However, receptor down regulation--a process that normally functions to attenuate Met signaling in vivo--could if impaired, amplify Met signaling in pancreatic tumor cells. Here we report that the lysosomal down regulation of Met is uncoupled in pancreatic adenocarcinoma cell lines. Interestingly, different endocytic mechanisms are employed to escape receptor down regulation and prolong Met signaling. Specifically, ligand treatment does not result in Met retention on the plasma membrane. Rather impaired binding of the E3 ubiquitin ligase Cbl to internalized Met in pancreatic Suit-2 cells causes reduced receptor ubiquitination and enhances Met recycling to the cell surface. Conversely, transient ligand-induced Met ubiquitination in pancreatic BxPC-3 cells correlates with prolonged Met stability and signaling. Moreover, increased Met stability and signaling enhances Suit-2 and BxPC-3 cell viability and chemotaxis towards Hepatocyte Growth Factor. Together our data indicate that uncoupled Met down regulation likely functions to amplify the oncogenic signaling of Met in pancreatic tumor cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1359-4117
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
297-312
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Altered down regulation of the receptor tyrosine kinase met in pancreatic adenocarcinoma cells.
pubmed:affiliation
Department of Neuroscience and Cell Biology, Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1074, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural