FoxM1 mediates resistance to herceptin and paclitaxel

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

Research output: Contribution to journalArticle

125 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

Fingerprint Dive into the research topics of 'FoxM1 mediates resistance to herceptin and paclitaxel'. Together they form a unique fingerprint.

  • Cite this

    Carr, J. R., Park, H. J., Wang, Z., Kiefer, M. M., & Raychaudhuri, P. (2010). FoxM1 mediates resistance to herceptin and paclitaxel. Cancer Research, 70(12), 5054-5063. https://doi.org/10.1158/0008-5472.CAN-10-0545