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Research ArticleExperimental Studies

Targeting of Focal Adhesion Kinase by Flavonoids and Small-interfering RNAs Reduces Tumor Cell Migration Ability

YING-TANG HUANG, LUNG-TA LEE, PING-PING H LEE, YUNG-SHENG LIN and MING-TING LEE
Anticancer Research May 2005, 25 (3B) 2017-2025;
YING-TANG HUANG
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LUNG-TA LEE
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PING-PING H LEE
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YUNG-SHENG LIN
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MING-TING LEE
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  • For correspondence: mtlee@gate.sinica.edu.tw
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Abstract

Focal adhesion kinase (FAK), a member of a growing family of structurally distinct protein tyrosine kinases (PTK), has been linked to specific phosphorylation events, and the elevation of FAK activity in human carcinoma cells is associated with increased invasive potential. In the present study, therefore, we developed two experiments to test the hypothesis that FAK is a determinant of, and plays an important role in, regulating tumor cell migration. In the first, the biological functions of FAK were examined using flavonoid inhibition. MiaPaCa-2 cells, treated with luteolin (Lu) and quercetin (Qu), were used to dampen FAK phosphorylation and protein expression by parallel suppression of cell migration ability. The second experiment involved suppression of FAK expression using small-interfering RNAs (siRNA) specific to FAK. While not affecting cellular proliferation or apoptosis, the siRNA targeting FAK almost completely inhibited FAK protein expression in MiaPaCa-2 cells and potently blocked the cell migration mediated by FAK. Our results show that FAK functions as a key regulator of cell migration, and that FAK activity can be suppressed by specific FAK siRNA, and by luteolin and quercetin. It appears reasonable to conclude, therefore, that suppression of FAK protein has a significant impact on tumor cell invasiveness.

  • Epidermal growth factor receptor
  • focal adhesion kinase
  • invasion
  • migration
  • flavonoids
  • siRNA

Footnotes

  • Abbreviations: DMSO, dimethyl sulphoxide; EGF, epidermal growth factor; ECL, enhanced chemiluminescence; FAK, focal adhesion kinase; MMP, matrix metalloproteinase; PTK, protein tyrosine kinase; SDS-PAGE, sodium dodecyl sulphate polyacrylamide gel electrophoresis.

  • Received November 12, 2004.
  • Revision received March 4, 2005.
  • Accepted March 9, 2005.
  • Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 25 (3B)
Anticancer Research
Vol. 25, Issue 3B
1 May 2005
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Targeting of Focal Adhesion Kinase by Flavonoids and Small-interfering RNAs Reduces Tumor Cell Migration Ability
YING-TANG HUANG, LUNG-TA LEE, PING-PING H LEE, YUNG-SHENG LIN, MING-TING LEE
Anticancer Research May 2005, 25 (3B) 2017-2025;

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Targeting of Focal Adhesion Kinase by Flavonoids and Small-interfering RNAs Reduces Tumor Cell Migration Ability
YING-TANG HUANG, LUNG-TA LEE, PING-PING H LEE, YUNG-SHENG LIN, MING-TING LEE
Anticancer Research May 2005, 25 (3B) 2017-2025;
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