FOXC1 Is a Potential Prognostic Biomarker with Functional Significance in Basal-like Breast Cancer

Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA.
Cancer Research (Impact Factor: 9.28). 05/2010; 70(10):3870-6. DOI: 10.1158/0008-5472.CAN-09-4120
Source: PubMed

ABSTRACT Gene expression signatures for a basal-like breast cancer (BLBC) subtype have been associated with poor clinical outcomes, but a molecular basis for this disease remains unclear. Here, we report overexpression of the transcription factor FOXC1 as a consistent feature of BLBC compared with other molecular subtypes of breast cancer. Elevated FOXC1 expression predicted poor overall survival in BLBC (P = 0.0001), independently of other clinicopathologic prognostic factors including lymph node status, along with a higher incidence of brain metastasis (P = 0.02) and a shorter brain metastasis-free survival in lymph node-negative patients (P < 0.0001). Ectopic overexpression of FOXC1 in breast cancer cells increased cell proliferation, migration, and invasion, whereas shRNA-mediated FOXC1 knockdown yielded opposite effects. Our findings identify FOXC1 as a theranostic biomarker that is specific for BLBC, offering not only a potential prognostic candidate but also a potential molecular therapeutic target in this breast cancer subtype.

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Available from: Ying Qu, Mar 02, 2014
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    • "These findings implicate BRCA1 and GATA3 corepress basal-like breast cancer genes D Tkocz et al FOXC1 as an important mediator of a number of aggressive traits associated with BLBCs and may offer opportunities to develop strategies to overcome drug resistance in this aggressive breast cancer subtype. FOXC1 has been previously identified as a poor prognostic indicator in BLBCs (Ray et al., 2010) and correlated with poor overall survival in BLBC independent of other clinicopathological prognostic factors including lymph node status. The FOXC1 gene has also been reported to be hypomethylated in CD44-positive breast cancer cells and was shown to induce a progenitor-like phenotype in differentiated mammary epithelial cells (Bloushtain-Qimron et al., 2008). "
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