title: Microtubule inhibition causes epidermal growth factor receptor inactivation             in oesophageal cancer cells.
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.
authors.affiliation: The Second Hospital of Nanjing affiliated to Southeast University, Nanjing, People's Republic of China. xuping_wu@yahoo.com
authors.forename: Xuping
authors.initials: X
authors.lastname: Wu
authors.forename: Linda
authors.initials: L
authors.lastname: Sooman
authors.forename: Johan
authors.initials: J
authors.lastname: Lennartsson
authors.forename: Stefan
authors.initials: S
authors.lastname: Bergström
authors.forename: Michael
authors.initials: M
authors.lastname: Bergqvist
authors.forename: Joachim
authors.initials: J
authors.lastname: Gullbo
authors.forename: Simon
authors.initials: S
authors.lastname: Ekman
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D047468:Immunoprecipitation; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017526:Receptor, IGF Type 1; D015398:Signal Transduction / Q000187:drug effects; D050257:Tubulin Modulators / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D050257:Tubulin Modulators; D014638:Vanadates; C512478:EGFR protein, human; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; D017027:Protein Tyrosine Phosphatases