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: 9.33). 05/2010; 70(10):3870-6. DOI: 10.1158/0008-5472.CAN-09-4120
Source: PubMed


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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    • "Humans with inherited haploinsufficiency of FOXC1 due to mutation or deletion exhibit the Axenfeld-Rieger syndrome, characterized by similar features to the murine knockout (Nishimura et al., 1998; Kume et al., 1998). High FOXC1 expression is associated with poor prognosis in breast and liver cancer (Ray et al., 2010; Xia et al., 2013), and its forced expression promotes an epithelialto-mesenchymal transition and enhanced proliferation, migration , invasion, and drug resistance, through downstream mediators such as NF-kB and NEDD9 (Bloushtain-Qimron et al., 2008; Wang et al., 2012; Xia et al., 2013). Interestingly, Foxc1 is highly expressed by Cxcl12-expressing adipo-osteogenic progenitors in mouse bone marrow (BM), and its deletion ablates hematopoietic stem cell (HSC) niches leading to reduced BM cellularity (Omatsu et al., 2014). "
    Cancer Cell 09/2015; · 23.52 Impact Factor
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    • "In HeLa cells, transcription factors JunB33 and FOXC134 were restricted in the perinuclear fraction; however, in MDA-MB-435 cells, these proteins were abundant in the nuclear fraction as well (Figures 2D and 3C). Nuclear FOXC1 in MDA-MB-435 also had a slow migratory component, but the perinuclear protein shows only one fast migratory band. "
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    • "Cluster 4 (blue-green) contained some cell cycle genes (CDC16, TFDP1). Cluster 5 (light-blue) contained FOXC1, a gene with regulatory and prognostic relevance in triple-negative breast cancer [41]. Cluster 6 (green) contained many genes that are related to ATPase activity (ATP5J, DHX15, CCT8, PSMC6 and ATP5O). "
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