Changes in cell morphology guide identification of tubulin as the off-target for protein kinase inhibitors.

Autor: Hoque M; The University of Sydney, Faculty of Medicine and Health, Charles Perkins Centre, NSW 2006, Australia., Abbassi RH; The University of Sydney, Faculty of Medicine and Health, Charles Perkins Centre, NSW 2006, Australia., Froio D; The Kinghorn Cancer Centre, The Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., Man J; The Kinghorn Cancer Centre, The Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., Johns TG; Oncogenic Signalling Laboratory and Brain Cancer Discovery Collaborative, Telethon Kids Institute, 100 Roberts Road, Subiaco, WA 6008, Australia., Stringer BW; QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia., Day BW; QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia., Pajic M; The Kinghorn Cancer Centre, The Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, NSW 2010, Australia., Kassiou M; The University of Sydney, School of Chemistry, NSW 2006, Australia., Munoz L; The University of Sydney, Faculty of Medicine and Health, Charles Perkins Centre, NSW 2006, Australia. Electronic address: lenka.munoz@sydney.edu.au.
Jazyk: angličtina
Zdroj: Pharmacological research [Pharmacol Res] 2018 Aug; Vol. 134, pp. 166-178. Date of Electronic Publication: 2018 Jun 23.
DOI: 10.1016/j.phrs.2018.06.023
Abstrakt: In the field of kinase inhibitors for applications in cancer research, tubulin is emerging as a targeted cellular protein that can significantly contribute to their activities. However, investigation of kinase inhibitors beyond the kinome is an area often neglected. Herein, we describe the results of pharmacological studies using drugs targeting kinases, tubulin or both. A key finding is that if cells are treated with a kinase inhibitor unintentionally targeting tubulin, their characteristic shape will diminish within a short timeframe. These changes in cell morphology are not seen when cells are treated with bona fide kinase inhibitors that do not directly target tubulin. Thus, early changes in cell morphology upon treatments are a strong indication that the inhibitor is directly targeting tubulin. Recognizing tubulin as a target of kinase inhibitors will build confidence in the future mechanistic studies using kinase inhibitors.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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