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THE AVISI0™ FOXC1 TECHNOLOGY
The Forkhead Box C1 Gene (FOXC1)
FOX (Forkhead box) C1 gene belongs to the forkhead family of transcription factors characterized by a distinct DNA-binding fork head domain. FOX proteins regulate the expression of genes involved in embryonic development, cell growth, proliferation, differentiation, and longevity. We have demonstrated:
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FOXC1 is an excellent theranostic biomarker specific for BLBC. [1]
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FOXC1 is superior to other reported BLBC - associated genes in identifying BLBC as shown via microarray analysis. [1] [Gene Microarray]
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BLBC tissue microarray samples stained positive with FOXC1 antibody IHC [1] [Gene Microarray] [FOXC1 IHC]
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Analysis of a microarray data set for a human breast cancer cell line panel revealed higher FOXC1 expression in BLBC cell lines, which was confirmed by immunoblotting. [BC cell culture] [Immunoblotting]
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Elevated FOXC1 mRNA expression is associated with poor overall survival. [1] [qRT-PCR] [Microarray data sample]
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High FOXC1 mRNA significantly correlated with shortened brain metastasis - free survival in node negative patients. [1] [qRT-PCR] [Microarray data sample]
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FOXC1 mRNA is consistently overexpressed in BLBC. [1][qRT-PCR] [Microarray data sample]
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Ectopic overexpression of FOXC1 in breast cancer cells induced aggressive phenotypes, increase cell proliferation, migration, and invasion. Knockdown of FOXC1 using shRNA demonstrated opposite effects. [1] [Breast Cancer Cell Culture]
Immunohistochemical detection of FOXC1 expression in TNP invasive breast cancer is an independent prognostic indicator that is superior to conventional immunohistochemical surrogates of BLBC. [2]
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No equivocal results. Positive expression of FOXC1 was a significant predictor of overall survival, independent of cutoff scores and other standard clinicopathologic factors. [2] [Archived patient samples] [FOXC1 IHC]
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BLBC defined by TNP plus FOXC1 demonstrated superior prognostic relevance compared to BLBC defined by TNP or TNP plus basal CKs. [2] [Archived patient samples] [FOXC1 IHC]
FOXC1 mediates PIN 1 expression, which in turn stabilizes p65/RelA protein and activates the transcription factor NF-κB in BLBC cells. [3] [Gene expression microarray data] [Immunoprecipitation] [Immunoblotting]
Identified a novel EGFR-FOXC1 signaling axis critical for BLBC cell function. [4]
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Both FOXC1 mRNA and protein levels significantly correlated with EGFR expression in human breast tumors. EGFR activation induced FOXC1 transcription through the ERK and Akt pathways in BLBC. EGFR inhibition in vivo reduced FOXC1 expression in xenograft tumors. We also found that FOXC1 knockdown impaired the effects of EGF on BLBC cell proliferation, migration, and invasion.[Immunoprecipitation] [Immunoblotting] [qRT-PCR] [Luciferase activity] [Xenograph]
FOXC1 IHC detection is a significant independent prognostic biomarker superior to existing surrogates. [5]
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FOXC1 overexpression reduces sensitivity to anti-Hedgehog inhibitors in BLBC cells. [6]
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FOXC1 expression on immunohistochemical staining is associated with BRCA1 vs BRCA2 mutations (30/46 vs. 6/35) [7]
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In cell culture models of BRCA1-mutant breast cancer, FOXC1 is associated with increased proliferation and may serve as a marker for sensitivity to PARP-inhibitor therapy with olaparib [7]
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Use of FOXC1 as a prognostic biomarker for Acute Myeologenous Leukemia. [8]
Partha S. Ray, MD
Founder, Director, Chairman-Med/Sci Advisory Board
We believe that FOXC1 imparts a property whereby the cell is specialized from the beginning. Contrary to other forms of cancer, requiring adaptation to environment before metastasis, BLBC tumors can be very small, do not clinically demonstrate spread to regional lymph nodes, but yet have already metastasized via the blood stream to distant organs, thus eluding detection until it is too late.
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