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Evaluation of FOXC1 as a therapeutic target for basal-like breast cancer.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 2018 May; Vol. 25 (3-4), pp. 84-91. Date of Electronic Publication: 2018 Mar 06. - Publication Year :
- 2018
-
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.
- Subjects :
- Animals
Cell Line, Tumor
Female
Mice
Neoplasm Metastasis
Forkhead Transcription Factors biosynthesis
Forkhead Transcription Factors genetics
Gene Expression Regulation, Neoplastic
Mammary Neoplasms, Animal genetics
Mammary Neoplasms, Animal metabolism
Mammary Neoplasms, Animal pathology
Mammary Neoplasms, Animal therapy
Neoplasm Proteins biosynthesis
Neoplasm Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5500
- Volume :
- 25
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 29511313
- Full Text :
- https://doi.org/10.1038/s41417-018-0010-9