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Evaluation of FOXC1 as a therapeutic target for basal-like breast cancer

Cancer Gene Therapy volume 25, pages 84–91 (2018)Cite this article

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Abstract

Basal-like breast cancer (BLBC) is a malignant carcinoma with aggressive motility and rapid growth. Accounting for 15% of breast cancers, BLBC often exhibits a poor prognosis and tends to metastasize to the brain and lungs. Because most BLBC display a triple-negative phenotype (ER-, PR-, and HER2-), conventional cytotoxic chemotherapy remains the only treatment option despite poor success and high rate of relapse. The overexpression of the forkhead-box transcription factor C1 (FOXC1) was recently identified as a biomarker of BLBC. Increased expression of FOXC1 was linked to excessive mobility and growth of BLBC cell lines, suggesting FOXC1 as a therapeutic target. In this study, siRNA-mediated knockdown of FOXC1 was confirmed to decrease the proliferation rate, migration, and invasion in a model BLBC-like cell line (4T1). 4T1 and 4T1-∆FOXC1 cells lacking FOXC1 expression (generated by CRISPR/Cas9) were used to evaluate the effects of FOXC1 expression in an orthotopic murine model of BLBC. No statistically significant difference in tumor volume was observed between 4T1 and 4T1-∆FOXC1 tumors. Furthermore, tumors metastasized to the liver and lungs to a similar degree regardless of FOXC1 expression. These data suggest that, despite positive results in vitro, FOXC1 may not be a promising therapeutic target for BLBC.

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Acknowledgements

This work was supported by start-up funds to DWP by the University of Kentucky.

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Authors and Affiliations

  1. Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY, 40506, USA

    Landon Mott & Daniel W. Pack

  2. Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, 40536, USA

    Kai Su & Daniel W. Pack

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  1. Landon Mott
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Correspondence to Daniel W. Pack.

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Mott, L., Su, K. & Pack, D.W. Evaluation of FOXC1 as a therapeutic target for basal-like breast cancer. Cancer Gene Ther 25, 84–91 (2018). https://doi.org/10.1038/s41417-018-0010-9

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