Extracellular pressure stimulates tumor cell adhesion in vitro by paxillin activation

van Zyp, J. V., Conway, W. C., Craig, D. H., van Zyp, N. V., Thamilselvan, V. and Basson, M. D. (2006) Extracellular pressure stimulates tumor cell adhesion in vitro by paxillin activation. Cancer biology & therapy, 5 9: 1169-1178.

Author van Zyp, J. V.
Conway, W. C.
Craig, D. H.
van Zyp, N. V.
Thamilselvan, V.
Basson, M. D.
Title Extracellular pressure stimulates tumor cell adhesion in vitro by paxillin activation
Journal name Cancer biology & therapy   Check publisher's open access policy
ISSN 1538-4047
Publication date 2006-09-01
Year available 2006
Sub-type Article (original research)
Volume 5
Issue 9
Start page 1169
End page 1178
Total pages 10
Place of publication Austin, TX, United States
Publisher Landes Bioscience
Language eng
Abstract Metastasizing colon cancer cells bind target tissues primarily via integrins. Extracellular pressure or shear stress stimulates integrin-mediated adhesion to matrix proteins or endothelial cells by activating the focal adhesion proteins FAK and Src. Because this effect is blocked by cytoskeletal perturbation and paxillin may link the cytoskeleton to the focal adhesion complex, we evaluated the role of paxillin in pressureinduced malignant colonocyte adhesion. We studied SW620 colon cancer cells and confirmed key results in Caco-2 colon cancer cells, primary human colon cancer cells, and a murine colonic adenocarcinoma. We evaluated adhesion to collagen at ambient and 15 mmHg increased pressure after 30 minutes, and paxillin, FAK, and Src phosphorylation in suspended cells prior to adhesion. Some cells were treated with siRNA to paxillin or FAK, or the Src inhibitor PP2. We also compared pressure-induced signals in suspended cells with adhesion-induced signals after adhesion to collagen. Pressure stimulated adhesion and paxillin phosphorylation in SW620 and Caco-2 cells and human primary colon cancer cells. Pressure also increased paxillin phosphorylation in murine carcinoma cells. SiRNA to paxillin decreased SW620 and Caco-2 paxillin without altering basal levels of phosphorylated paxillin. Paxillin reduction decreased basal adhesion to collagen, and inhibited pressure-stimulated adhesion, as well as paxillin, FAK397, FAK576, and Src476 phosphorylation. Neither PP2 nor siRNA to FAK inhibited induction of paxillin phosphorylation by pressure. In contrast, adhesion stimulated FAK, Src, and paxillin phosphorylation regardless of paxillin reduction. In summary, pressure induced paxillin phosphorylation in colon cancer cells. Paxillin reduction inhibited basal adhesion and blocked the pressure-mediated increase in adhesion, as well as pressure-induced FAK and Src signals, while adhesion-induced signals were preserved. Paxillin may be an upstream mediator of pressure-stimulated adhesion, important in metastasis.
Keyword paxillin
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID R01DK06771
T32 GM008420
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 14 Mar 2011, 18:52:58 EST