Disruption of FAK signaling: a side mechanism in cytotoxicity

Toxicology
Nikolaos A ChatzizachariasStamatios E Theocharis

Abstract

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase (PTK) which acts as an early modulator in the integrin signaling cascade. FAK phosphorylation and its consequent activation regulate several basic biological cellular functions. On the contrary, dysregulation of FAK signaling is implicated in the malignant transformation of cells, as well as in nonmalignant pathological conditions. With respect to cytotoxicity, accumulating data indicate that FAK participates in the mechanism of action of the known cytotoxic reactive oxygen species (ROS). Additionally, evidence was presented that different cytotoxic substances, such as arsenic (As), lead (Pb), acrylamide, methylisothiazolinone (MIT), dichlorovinylcysteine (DCVC) and halothane, acted, at least in part, by downregulating FAK tyrosine phosphorylation, while the bacterial toxins Pasteurella multocida toxin and Escherichia coli cytotoxic necrotizing factor, have been shown to exert cytotoxic effects by inducing FAK tyrosine phosphorylation. The observation that upregulation as well as downregulation of FAK activity both result in cytotoxic effects seems contradictory. Even though a common mode of action, with respect to the dysregulation of FAK signaling, for thes...Continue Reading

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Citations

Apr 21, 2010·Pathology Oncology Research : POR·Christina MichailidiStamatios Theocharis
Jun 8, 2013·Biotechnology and Bioengineering·José Ballester-BeltránManuel Salmerón-Sánchez
May 12, 2012·Gene·William R ThompsonJanet Rubin
Jun 23, 2011·Biochemical and Biophysical Research Communications·Bing WangXinsheng Cao
Jul 30, 2014·Scientific Reports·Aleixandre Rodrigo-NavarroManuel Salmeron-Sanchez
Mar 7, 2013·Journal of Cellular Biochemistry·Grace ChoongDouglas M Templeton
Jan 29, 2010·Molecular Reproduction and Development·Michelle F Goody, Clarissa A Henry
Dec 5, 2014·Expert Opinion on Therapeutic Targets·Christos BikisStamatios Theocharis

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