Microtubule inhibition causes epidermal growth factor receptor inactivation in oesophageal cancer cells

Wu,Xuping; Sooman,Linda; Lennartsson,Johan; Bergström,Stefan; Bergqvist,Michael; Gullbo,Joachim; Ekman,Simon

doi:10.3892/ijo.2012.1710

Microtubule inhibition causes epidermal growth factor receptor inactivation in oesophageal cancer cells

Authors:
- Xuping Wu
- Linda Sooman
- Johan Lennartsson
- Stefan Bergström
- Michael Bergqvist
- Joachim Gullbo
- Simon Ekman
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Affiliations: The Second Hospital of Nanjing affiliated to Southeast University, 210003 Nanjing, P.R. China, Section of Oncology, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, SE-75185 Uppsala, Sweden, Ludwig Institute for Cancer Research, Uppsala University, SE-75124 Uppsala, Sweden, Department of Medical Sciences, Division of Clinical Pharmacology, Uppsala University, SE-75185 Uppsala, Sweden
Published online on: November 20, 2012 https://doi.org/10.3892/ijo.2012.1710
Pages: 297-304

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Abstract

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 phosphatase (PTP) that can regulate EGFR phosphorylation and activation, an effect of potential clinical relevance for combination therapies in patients.

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