FoxM1 mediates resistance to herceptin and paclitaxel

Janai R. Carr, Hyun Jung Park, Zebin Wang, Megan M. Kiefer, Pradip Raychaudhuri

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

Inherent and acquired therapeutic resistance in breast cancer remains a major clinical challenge. In human breast cancer samples, overexpression of the oncogenic transcription factor FoxM1 has been suggested to be a marker of poor prognosis. In this study, we report that FoxM1 overexpression confers resistance to the human epidermal growth factor receptor 2 monoclonal antibody Herceptin and microtubule-stabilizing drug paclitaxel, both as single agents and in combination. FoxM1 altered microtubule dynamics to protect tumor cells from paclitaxel-induced apoptosis. Mechanistic investigations revealed that the tubulin-destabilizing protein Stathmin, whose expression also confers resistance to paclitaxel, is a direct transcriptional target of FoxM1. Significantly, attenuating FoxM1 expression by small interfering RNA or an alternate reading frame (ARF)-derived peptide inhibitor increased therapeutic sensitivity. Our findings indicate that targeting FoxM1 could relieve therapeutic resistance in breast cancer.

Original languageEnglish (US)
Pages (from-to)5054-5063
Number of pages10
JournalCancer Research
Volume70
Issue number12
DOIs
StatePublished - Jun 15 2010
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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