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Microtubule inhibition causes epidermal growth factor receptor inactivation in oesophageal cancer cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
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2013 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 42, no 1, 297-304 p.Article in journal (Refereed) Published
Abstract [en]

Drugs that interfere with microtubule function can prevent cells from mitosis and may cause cell cycle arrest or apoptosis. Various microtubule targeting agents, both stabilizers and inhibitors, are used in a clinical setting to treat cancer. In the current study, we investigated the sensitivity of oesophageal cancer cells to different microtubule targeting agents. The current study demonstrated that different microtubule targeting agents disrupted the microtubule network and inhibited survival of oesophageal cancer cells in a dose-dependent manner. Interestingly, an additional cellular effect with inhibition of tyrosine phosphorylation of the EGFR and subsequent downregulation of EGFR-induced signalling was also observed, suggesting an additional mechanism of action for microtubule destabilising agents. A tyrosine phosphatase inhibitor, sodium orthovanadate, could reverse the EGFR dephosphorylation effects induced by microtubule targeting agents. The EGFR dephosphorylation could be reversed by a tyrosine phosphatase inhibitor, indicating that disruption of the microtubule network may lead to activation of a protein tyrosine phosphatasc (PTP) that can regulate EGFR phosphorylation and activation, an effect of potential clinical relevance for combination therapies in patients.

Place, publisher, year, edition, pages
2013. Vol. 42, no 1, 297-304 p.
Keyword [en]
microtubule targeting agents, epidermal growth factor, tyrosine phosphatase, oesophageal cancer cells
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-192442DOI: 10.3892/ijo.2012.1710ISI: 000312566900034OAI: oai:DiVA.org:uu-192442DiVA: diva2:600314
Available from: 2013-01-24 Created: 2013-01-21 Last updated: 2017-12-06Bibliographically approved

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Wu, XupingSooman, LindaLennartsson, JohanBergqvist, MichaelGullbo, Joachim

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