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RETRACTED ARTICLE: FoxM1 down-regulation leads to inhibition of proliferation, migration and invasion of breast cancer cells through the modulation of extra-cellular matrix degrading factors

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This article was retracted on 13 July 2016

Abstract

Forkhead box M1 (FoxM1) transcription factor is known to play important role in human cancers which, in part, is mediated by its ability to modulate cell cycle regulatory proteins as well as genes involved in cell proliferation and differentiation. In breast cancer, FoxM1 down-regulation is increasingly being recognized as an important mechanism for the targeted activity of anti-cancer agents. However, the mechanistic insight in support of the role of FoxM1 in aggressive breast cancer is poorly understood. We have tested the biological consequence of FoxM1 down-regulation and up-regulation in breast cancer cell lines and found that the down-regulation of FoxM1 in MDA-MB-231 and SUM149 cells by siRNA approach inhibited cell growth, clonogenicity, migration, and invasion. We also found decreased expression of CDK2 and E2F1 with concomitant increase in p21 and p27 proteins, suggesting an important role of FoxM1 in cell cycle progression. In contrast, over-expression of FoxM1 by cDNA transfection, in breast cancer cells (SUM102 and SKBR3) expressing low levels of FoxM1, resulted in increased cell proliferation, migration, and invasion. Moreover, down-regulation of FoxM1 inhibited the expression of many factors that are involved in the degradation of extra cellular matrix and angiogenesis such as uPA, uPAR, MMP-2, MMP-9, and vascular endothelial growth factor (VEGF) as well as inhibited the activity of MMP-9 and VEGF. Interestingly, over-expression of uPA by cDNA transfection abrogated the cellular effects that were observed by the down-regulation of FoxM1. Taken together, these results suggest the potential application of FoxM1 down-regulation as a novel approach for the treatment of aggressive breast cancer.

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Authors and Affiliations

  1. Department of Pathology, Barbara Ann Karmanos Cancer Center, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Aamir Ahmad, Zhiwei Wang, Dejuan Kong, Shadan Ali, Yiwei Li, Sanjeev Banerjee, Raza Ali & Fazlul H. Sarkar

  2. Department of Pathology, Karmanos Cancer Institute, 740 HWCRC Bldg, 4160 John R. Street, Detroit, MI, 48201, USA

    Fazlul H. Sarkar

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  1. Aamir Ahmad
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  2. Zhiwei Wang
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  3. Dejuan Kong
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  4. Shadan Ali
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  8. Fazlul H. Sarkar
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Correspondence to Fazlul H. Sarkar.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s10549-016-3904-y.

The paper is retracted at the request of the publisher because in Figs. 5a and 5b, and 6c micrograph images are re-used and re-labeled to represent different conditions.

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Ahmad, A., Wang, Z., Kong, D. et al. RETRACTED ARTICLE: FoxM1 down-regulation leads to inhibition of proliferation, migration and invasion of breast cancer cells through the modulation of extra-cellular matrix degrading factors. Breast Cancer Res Treat 122, 337–346 (2010). https://doi.org/10.1007/s10549-009-0572-1

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  • DOI: https://doi.org/10.1007/s10549-009-0572-1

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