Stathmin, a phosphoprotein that modulates microtubule dynamics, is highly expressed in breast cancer cells. Eribulin, a microtubule‐depolymerizing agent, is used to treat patients with advanced breast cancer. However, the detailed mechanisms underlying the action of eribulin during microtubule catastrophe, and the interaction between eribulin and stathmin dynamics, remain unclear. Here, we investigated the role of stathmin in the antiproliferative activity of eribulin in breast cancer cells. Eribulin induced phosphorylation of stathmin in MCF7 and MDA‐MB‐231 cells; this was attenuated by an inhibitor of protein kinase A (H89) and an inhibitor of Ca 2+ /calmodulin‐dependent kinase II (KN62). In addition, expression of phosphorylated stathmin was reduced by the protein phosphatase PP2A activator FTY720 but increased by the PP2A inhibitor okadaic acid. Of note, expression of PP2A subunits in eribulin‐treated cells decreased, although eribulin did not affect the phosphatase activity of recombinant PP2A directly. Furthermore, the antiproliferative effect of eribulin was stronger in stathmin‐overexpressing cells. These results suggest that stathmin dynamics are closely associated with the antiproliferative effects of eribulin and stathmin is a possible biomarker for predicting the therapeutic effects of eribulin in breast cancer patients.

Stathmin is a member of microtubule destabilizing proteins that modulate the dynamics of microtubule polymerization and depolymerization. Stathmin promotes microtubule depolymerization and the activity was regulated by its phosphorylation state. It has been reported that high stathmin expression is associated with poor prognosis in breast cancer patients. Eribulin, an analogue of the marine natural product halichondrin B, is a microtubule-depolymerizing drug that has been used in the treatment of patients with advanced breast cancer. In this study, we examined the involvement of stathmin in the antiproliferative activities of eribulin in breast cancer cells (MCF7 and MDA-MB-231). Eribulin induced phosphorylation of stathmin in both cells. The eribulin-mediated phosphorylation of stathmin was attenuated by the inhibitors of protein kinase A (H89) and Ca 2+ /calmodulindependent kinase II (KN62). In addition, the phosphorylated stathmin was reduced by the protein phosphatase PP2A activator FTY720, whereas it was increased by the PP2A inhibitor okadaic acid. Of note, eribulin did not directly affect the phosphatase activity of recombinant PP2A, but the expression of PP2A subunits was reduced in eribulintreated cells. Furthermore, the antiproliferative effect of eribulin was more efficient in stathmin-overexpressing cells compared to control. Together these data provide a novel mechanism of antiproliferative effects of eribulin which is mediated through stathmin dynamics in breast cancer cells. Student Sessions