TY - JOUR
T1 - Focal adhesion kinase (FAK) phosphorylation is not required for genistein-induced FAK-β-1-integrin complex formation
AU - Liu, Yueqin
AU - Kyle, Edward
AU - Lieberman, Ronald
AU - Crowell, James
AU - Kelloff, Gary
AU - Bergan, Raymond C.
PY - 2000
Y1 - 2000
N2 - It has previously been shown that changes in the activity of focal adhesion kinase (FAK), and its binding to β-1-integrin, accompany genistein-induced adhesion of prostate cells. Consumption of genistein world wide is associated with a lower incidence of metastatic prostate cancer. Early human clinical trials of genistein are under way to evaluate genistein's potential causal role in this regard. Though an important cell adhesion-associated signaling molecule, FAK's role in regulating prostate cell adhesion was not clear. Elucidation of this process would provide important information relating to both biology and potential clinical endpoints. It was hypothesized that FAK activation and complex formation are temporally related in prostate cells, and can thus be separated. Significant activation of FAK was demonstrated when cells adhered to fibronectin, as compared to poly-L-lysine, thus demonstrating that β-1-integrin plays a significant role in activating FAK. Neither FAK activation, nor FAK-integrin complex formation, required β-1-integrin ligand. However, disruption of the cellular cytoskeleton by cytochalasin D prevented FAK activation, but did not block genistein-induced complex formation. In the face of a disrupted cytoskeleton, signaling through FAK could not be restored through either integrin cross linking, or re-establishment of tensile forces via attachment to solid matrix. These studies demonstrate that FAK-β-1-integrin complex formation does not require FAK activation, suggesting that it is an early event in prostate cell adhesion. An intact cytoskeleton is necessary for FAK activation. The functional importance of β-1-integrin in prostate cells is demonstrated. Current findings support plans to test genistein in prostate cancer.
AB - It has previously been shown that changes in the activity of focal adhesion kinase (FAK), and its binding to β-1-integrin, accompany genistein-induced adhesion of prostate cells. Consumption of genistein world wide is associated with a lower incidence of metastatic prostate cancer. Early human clinical trials of genistein are under way to evaluate genistein's potential causal role in this regard. Though an important cell adhesion-associated signaling molecule, FAK's role in regulating prostate cell adhesion was not clear. Elucidation of this process would provide important information relating to both biology and potential clinical endpoints. It was hypothesized that FAK activation and complex formation are temporally related in prostate cells, and can thus be separated. Significant activation of FAK was demonstrated when cells adhered to fibronectin, as compared to poly-L-lysine, thus demonstrating that β-1-integrin plays a significant role in activating FAK. Neither FAK activation, nor FAK-integrin complex formation, required β-1-integrin ligand. However, disruption of the cellular cytoskeleton by cytochalasin D prevented FAK activation, but did not block genistein-induced complex formation. In the face of a disrupted cytoskeleton, signaling through FAK could not be restored through either integrin cross linking, or re-establishment of tensile forces via attachment to solid matrix. These studies demonstrate that FAK-β-1-integrin complex formation does not require FAK activation, suggesting that it is an early event in prostate cell adhesion. An intact cytoskeleton is necessary for FAK activation. The functional importance of β-1-integrin in prostate cells is demonstrated. Current findings support plans to test genistein in prostate cancer.
KW - Cell adhesion
KW - Focal adhesion kinase
KW - Genistein
KW - Integrin
KW - Prostate cancer
KW - Tyrosine kinase inhibitor
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U2 - 10.1023/A:1006729106034
DO - 10.1023/A:1006729106034
M3 - Article
C2 - 11315093
AN - SCOPUS:0035062953
SN - 0262-0898
VL - 18
SP - 203
EP - 212
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 3
M1 - 314850
ER -