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

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.