The effects of inducible overexpression of FAK-related non-kinase (FRNK) on a transformed epithelial cell line.
Focal adhesion kinase (FAK), which has received much attention as a transducer of integrin-mediated signals, is overexpressed in several types of human cancer. FAK-related non-kinase (FRNK) is an autonomously expressed carboxyl-terminal region of FAK, which acts as an inhibitor of FAK function. In order to determine the role of FAK/FRNK in cancer, we constructed a transformed human embryonic kidney cell line (293), which overexpressess FRNK in an inducible manner. Cells that overexpress FRNK have reduced adhesion-mediated tyrosine phosphorylation of FAK with a coincident decrease in ERK phosphorylation. FRNK overexpression did not restore anoikis to these transformed cells. However, FRNK overexpression did sensitize cells to the cytotoxic effect of 5-fluorouracil and led to a decrease in haptotactic mobility. We conclude that in these transformed cells the predominant effect of FAK is on cell migration. Additionally, overexpression of FRNK may provide therapeutic benefits by enhancing the cytotoxic effects of chemotherapeutic agents.
Kornberg
Lori
L
Department of Otolaryngology, Box 100264, 1600 SW Archer Road, Room M-228, University of Florida, Gainesville, FL 32610, USA.
Fleigel
Jeffery
J
D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004318:Doxycycline / Q000494:pharmacology; D004789:Enzyme Activation; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D005472:Fluorouracil / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007668:Kidney / Q000166:cytology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D004318:Doxycycline; D005472:Fluorouracil