Linked Life Data

20937825

Source:http://linkedlifedata.com/resource/pubmed/id/20937825

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
2010-12-14
pubmed:abstractText
The Abl tyrosine kinases, Abl and Arg, play a role in the regulation of the actin cytoskeleton by modulating cell-cell adhesion and cell motility. Deregulation of both the actin cytoskeleton and Abl kinases have been implicated in cancers. Abl kinase activity is elevated in a number of metastatic cancers and these kinases are activated downstream of several oncogenic growth factor receptor signaling pathways. However, the role of Abl kinases in regulation of the actin cytoskeleton during tumor progression and invasion remains elusive. Here we identify the Abl kinases as essential regulators of invadopodia assembly and function. We show that Abl kinases are activated downstream of the chemokine receptor, CXCR4, and are required for cancer cell invasion and matrix degradation induced by SDF1?, serum growth factors, and activated Src kinase. Moreover, Abl kinases are readily detected at invadopodia assembly sites and their inhibition prevents the assembly of actin and cortactin into organized invadopodia structures. We show that active Abl kinases form complexes with membrane type-1 matrix metalloproteinase (MT1-MMP), a critical invadopodia component required for matrix degradation. Further, loss of Abl kinase signaling induces internalization of MT1-MMP from the cell surface, promotes its accumulation in the perinuclear compartment and inhibits MT1-MMP tyrosine phosphorylation. Our findings reveal that Abl kinase signaling plays a critical role in invadopodia formation and function, and have far-reaching implications for the treatment of metastatic carcinomas.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CXCL12 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CXCR4 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CXCR4 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL12, http://linkedlifedata.com/resource/pubmed/chemical/Cxcl12 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/MMP14 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 14, http://linkedlifedata.com/resource/pubmed/chemical/Mmp14 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-abl, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CXCR4, http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
40201-11
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Abl kinases are required for invadopodia formation and chemokine-induced invasion.
pubmed:affiliation
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural