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

123 Citations (Scopus)

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

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Paclitaxel
Breast Neoplasms
Microtubules
Stathmin
Reading Frames
Tubulin
Small Interfering RNA
Transcription Factors
Therapeutics
Monoclonal Antibodies
Apoptosis
Peptides
Pharmaceutical Preparations
Trastuzumab
Neoplasms
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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

FoxM1 mediates resistance to herceptin and paclitaxel. / Carr, Janai R.; Park, Hyun Jung; Wang, Zebin; Kiefer, Megan M.; Raychaudhuri, Pradip.

In: Cancer Research, Vol. 70, No. 12, 15.06.2010, p. 5054-5063.

Research output: Contribution to journalArticle

Carr, JR, Park, HJ, Wang, Z, Kiefer, MM & Raychaudhuri, P 2010, 'FoxM1 mediates resistance to herceptin and paclitaxel', Cancer Research, vol. 70, no. 12, pp. 5054-5063. https://doi.org/10.1158/0008-5472.CAN-10-0545
Carr JR, Park HJ, Wang Z, Kiefer MM, Raychaudhuri P. FoxM1 mediates resistance to herceptin and paclitaxel. Cancer Research. 2010 Jun 15;70(12):5054-5063. https://doi.org/10.1158/0008-5472.CAN-10-0545
Carr, Janai R. ; Park, Hyun Jung ; Wang, Zebin ; Kiefer, Megan M. ; Raychaudhuri, Pradip. / FoxM1 mediates resistance to herceptin and paclitaxel. In: Cancer Research. 2010 ; Vol. 70, No. 12. pp. 5054-5063.
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