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Stathmin expression alters the antiproliferative effect of eribulin in leiomyosarcoma cells

Mana Azumi1, Mikihiro Yoshie1, Nami Nakachi1

  • 1Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.

Journal of Pharmacological Sciences
|November 7, 2022
PubMed

Insights

Stathmin protein levels influence eribulin effectiveness in uterine leiomyosarcoma. Lower stathmin expression correlates with eribulin resistance, suggesting stathmin is key to treatment efficacy.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Uterine leiomyosarcoma is an aggressive malignancy.
  • Stathmin, a microtubule-modulating phosphoprotein, is highly expressed in leiomyosarcoma.
  • Eribulin, a microtubule-depolymerizing agent, is approved for soft tissue tumors.

Purpose of the Study:

  • To investigate the role of stathmin expression in the efficacy of eribulin treatment for uterine leiomyosarcoma.
  • To elucidate the relationship between eribulin and stathmin dynamics in leiomyosarcoma cells.

Main Methods:

  • Examined eribulin's effects on stathmin phosphorylation and protein phosphatase 2A (PP2A) expression in leiomyosarcoma cells.
  • Utilized a PP2A activator (FTY720) to assess its impact on phosphorylated stathmin.
  • Assessed stathmin mRNA and protein levels following eribulin treatment.
  • Investigated the effects of stathmin knockdown and overexpression on eribulin's anti-proliferative activity.
  • Analyzed molecular markers in eribulin-resistant leiomyosarcoma cell lines.

Main Results:

  • Eribulin induced stathmin phosphorylation and decreased PP2A subunits A and C.
  • FTY720 reduced phosphorylated stathmin levels.
  • Eribulin decreased stathmin protein but not mRNA levels.
  • Stathmin knockdown reduced eribulin's inhibitory effect on cell viability; stathmin overexpression enhanced it.
  • Eribulin-resistant cells showed decreased stathmin and increased TUBB1, MDR1, and BCRP expression.

Conclusions:

  • Stathmin expression levels modulate the anti-cancer effects of eribulin in uterine leiomyosarcoma.
  • Stathmin may serve as a predictive biomarker for eribulin response in uterine leiomyosarcoma treatment.
Keywords:
EribulinLeiomyosarcomaMicrotubulePP2AStathmin

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