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Inhibition of cell migration and cell division correlates with distinct effects of microtubule inhibiting drugs.


ABSTRACT: Drugs that target microtubules are thought to inhibit cell division and cell migration by suppressing dynamic instability, a "search and capture" behavior that allows microtubules to probe their environment. Here, we report that subtoxic drug concentrations are sufficient to inhibit plus-end microtubule dynamic instability and cell migration without affecting cell division or microtubule assembly. The higher drug concentrations needed to inhibit cell division act through a novel mechanism that generates microtubule fragments by stimulating microtubule minus-end detachment from their organizing centers. The frequency of microtubule detachment in untreated cells increases at prophase suggesting that it is a regulated cellular process important for spindle assembly and function. We conclude that drugs produce differential dose-dependent effects at microtubule plus and minus-ends to inhibit different microtubule-mediated functions.

SUBMITTER: Yang H 

PROVIDER: S-EPMC2952225 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Inhibition of cell migration and cell division correlates with distinct effects of microtubule inhibiting drugs.

Yang Hailing H   Ganguly Anutosh A   Cabral Fernando F  

The Journal of biological chemistry 20100809 42


Drugs that target microtubules are thought to inhibit cell division and cell migration by suppressing dynamic instability, a "search and capture" behavior that allows microtubules to probe their environment. Here, we report that subtoxic drug concentrations are sufficient to inhibit plus-end microtubule dynamic instability and cell migration without affecting cell division or microtubule assembly. The higher drug concentrations needed to inhibit cell division act through a novel mechanism that g  ...[more]

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