TY - JOUR
T1 - FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer
AU - Ray, Partha S.
AU - Wang, Jinhua
AU - Qu, Ying
AU - Sim, Myung Shin
AU - Shamonki, Jaime
AU - Bagaria, Sanjay P.
AU - Ye, Xing
AU - Liu, Bingya
AU - Elashoff, David
AU - Hoon, Dave S.
AU - Walter, Michael A.
AU - Martens, John W.
AU - Richardson, Andrea L.
AU - Giuliano, Armando E.
AU - Cui, Xiaojiang
PY - 2010/5/15
Y1 - 2010/5/15
N2 - 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.
AB - 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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U2 - 10.1158/0008-5472.CAN-09-4120
DO - 10.1158/0008-5472.CAN-09-4120
M3 - Article
C2 - 20406990
AN - SCOPUS:77952821751
SN - 0008-5472
VL - 70
SP - 3870
EP - 3876
JO - Cancer Research
JF - Cancer Research
IS - 10
ER -