Chemotherapeutic targeting of microtubules causes epidermal growth factor receptor dephosphorylation
(English)Article in journal (Other academic) Submitted
Microtubules are important structures for a range of cellular functions including cell division. Drugs that interfere with microtubule function can prevent cells from mitosis and various microtubule targeting drugs are used in a clinical setting. In the current study we investigated the sensitivity of oesophageal cancer cells to different microtubule targeting agents. As expected, experiments demonstrated that these agents in a dose-dependent manner inhibited survival and proliferation of oesophageal cancer cells and disrupted the microtubule network. Unexpectedly, experiments showed that microtubule destabilising agents inhibited phosphorylation and activation of the EGF-receptor, and that a tyrosine phosphatase inhibitor, sodium orthovanadate, could reverse the EGFR dephosphorylation. We propose a model in which disruption of the microtubule network leads to activation of a protein tyrosine phosphatase that can regulate EGFR phosphorylation and activation, indicating an additional mechanism of action of microtubule targeting agents.
IdentifiersURN: urn:nbn:se:uu:diva-152763OAI: oai:DiVA.org:uu-152763DiVA: diva2:413971