Src protein kinase pp60c-src influences adhesion stabilization of HT-29 colon carcinoma cells to extracellular matrix components under dynamic conditions of laminar flow
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Src protein kinase pp60c-src influences adhesion stabilization of HT-29 colon carcinoma cells to extracellular matrix components under dynamic conditions of laminar flow. / Haier, Jörg; Gallick, Garry E; Nicolson, Garth L.
In: THER ADV MED ONCOL, Vol. 2, No. 4, 06.11.2002, p. 237-45.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Src protein kinase pp60c-src influences adhesion stabilization of HT-29 colon carcinoma cells to extracellular matrix components under dynamic conditions of laminar flow
AU - Haier, Jörg
AU - Gallick, Garry E
AU - Nicolson, Garth L
PY - 2002/11/6
Y1 - 2002/11/6
N2 - Tumor cell adhesion to extracellular matrix (ECM) and its stabilization are important determinants in metastasis formation, and they are mediated, in part, by integrins and regulated by a variety of protein kinases. Protein tyrosine kinase pp60c-src is found in adhesion-dependent focal adhesion plaques where it may regulate different integrin-mediated signaling cascades. Using human HT-29 colon carcinoma cells stably transfected with pp60c-src--specific antisense oligonucleotides (HT-29AS15), we investigated the role of pp60c-src in integrin-mediated adhesion and its stabilization to ECM components collagen I or IV under static and laminar fluid flow conditions. Under static adhesion conditions transfection of pp60c-src antisense oligonucleotides did not modify adhesive properties. Phosphorylation of focal adhesion kinase (FAK) and paxillin induced by static adhesion to collagen I or IV were similar in HT-29P and HT-29AS15 cells. However, using hydrodynamic conditions in a laminar flow chamber we found a slight reduction in early adhesion events and an even greater difference in adhesion stabilization rates (ASRs). The transfected cells showed a significant reduction in their ability to withstand shear forces and stabilize adhesive bounds. These changes correlated with the cellular expression levels of pp60c-src. Our results suggest that pp60c-src may be involved in stabilization of dynamic HT-29 cell adhesion to ECM components, and this kinase appears to be part of a mechanosensory protein complex during integrin-mediated cell adhesion.
AB - Tumor cell adhesion to extracellular matrix (ECM) and its stabilization are important determinants in metastasis formation, and they are mediated, in part, by integrins and regulated by a variety of protein kinases. Protein tyrosine kinase pp60c-src is found in adhesion-dependent focal adhesion plaques where it may regulate different integrin-mediated signaling cascades. Using human HT-29 colon carcinoma cells stably transfected with pp60c-src--specific antisense oligonucleotides (HT-29AS15), we investigated the role of pp60c-src in integrin-mediated adhesion and its stabilization to ECM components collagen I or IV under static and laminar fluid flow conditions. Under static adhesion conditions transfection of pp60c-src antisense oligonucleotides did not modify adhesive properties. Phosphorylation of focal adhesion kinase (FAK) and paxillin induced by static adhesion to collagen I or IV were similar in HT-29P and HT-29AS15 cells. However, using hydrodynamic conditions in a laminar flow chamber we found a slight reduction in early adhesion events and an even greater difference in adhesion stabilization rates (ASRs). The transfected cells showed a significant reduction in their ability to withstand shear forces and stabilize adhesive bounds. These changes correlated with the cellular expression levels of pp60c-src. Our results suggest that pp60c-src may be involved in stabilization of dynamic HT-29 cell adhesion to ECM components, and this kinase appears to be part of a mechanosensory protein complex during integrin-mediated cell adhesion.
KW - Cell Adhesion
KW - Collagen
KW - Colorectal Neoplasms
KW - Cytoskeletal Proteins
KW - Extracellular Matrix
KW - Focal Adhesion Kinase 1
KW - Focal Adhesion Protein-Tyrosine Kinases
KW - HT29 Cells
KW - Humans
KW - Paxillin
KW - Phosphoproteins
KW - Phosphorylation
KW - Protein-Tyrosine Kinases
KW - Proto-Oncogene Proteins pp60(c-src)
KW - Stress, Mechanical
KW - Tumor Cells, Cultured
M3 - SCORING: Journal article
C2 - 12416028
VL - 2
SP - 237
EP - 245
JO - THER ADV MED ONCOL
JF - THER ADV MED ONCOL
SN - 1758-8340
IS - 4
ER -