Targeting of focal adhesion kinase by flavonoids and small-interfering RNAs reduces tumor cell migration ability.
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.
Huang
Ying-Tang
YT
Department of Marine Biotechnology, National Kaohsiung Marine University, Kaohsiung, Taiwan.
Lee
Lung-Ta
LT
Lee
Ping-Ping H
PP
Lin
Yung-Sheng
YS
Lee
Ming-Ting
MT
D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000628:therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011794:Quercetin / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection
D034741:RNA, Small Interfering; D011794:Quercetin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D047311:Luteolin