Linked Life Data

17317726

Source:http://linkedlifedata.com/resource/pubmed/id/17317726

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2007-5-31
pubmed:abstractText
Cancer cell adhesion is traditionally viewed as random, occurring if the cell's receptors match the substrate. Cancer cells are subjected to pressure and shear during growth against a constraining stroma, surgical manipulation, and passage through the venous and lymphatic system. Cells shed into a cavity such as the abdomen postoperatively also experience increased pressure from postoperative edema. Increased extracellular pressure stimulates integrin-mediated cancer cell adhesion via FAK and Src. PI 3-kinase (PI3K) inhibitors (LY294002 or wortmannin), Akt inhibitors, or Akt1 siRNA blocked adhesion stimulated by 15 mmHg pressure in SW620 or primary human malignant colonocytes. Pressure activated PI3K, tyrosine-phosphorylated and membrane-translocated the p85 subunit, and phosphorylated Akt. PI3K inhibitor (LY294002) prevented pressure-stimulated Akt Ser473 and FAK Tyr397, but not FAK576 or Src416 phosphorylation. PP2 inhibited PI3K activity and Akt phosphorylation. FAK siRNA did not affect pressure-induced PI3K activation but blocked Akt phosphorylation. Pressure also stimulated FAK or FAKY397F mutant translocation to the membrane. Akt inhibitor IV blocked pressure-induced Akt and FAK translocation. Pressure activated Src- and PI3K-dependently induced p85 interaction with FAK, and FAK with beta1 integrin. These results delineate a novel force-activated inside-out Src/PI3K/FAK/Akt pathway by which cancer cells regulate their own adhesion. These signals may be potential targets for inhibition of metastatic adhesion.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1730-41
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
FAK association with multiple signal proteins mediates pressure-induced colon cancer cell adhesion via a Src-dependent PI3K/Akt pathway.
pubmed:affiliation
Department of Surgery, John D. Dingell VA Medical Center, 4646 John R. St., Detroit, Michigan 48201-1932, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural