Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer cells through enhancing epidermal growth factor receptor stability
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Catherine A. Powell1, Mohd W. Nasser1, Helong Zhao1, Jacob C. Wochna1, Xiaoli Zhang2, Charles Shapiro3, Konstantin Shilo1 and Ramesh K. Ganju1
1 Department of Pathology, The Ohio State University, Columbus, OH, USA
2 Center for Biostatistics, The Ohio State University, Columbus, OH, USA
3 Tisch Cancer Institute, Mount Sinai School of Medicine, New York, USA
Ramesh K. Ganju, email:
Keywords: Fatty acid binding protein 5, triple negative breast cancer, epidermal growth factor receptor, protein degradation, metastasis
Received: December 16, 2014 Accepted: January 12, 2015 Published: January 31, 2015
Fatty acid binding protein 5 (FABP5), an intracellular lipid binding protein, has been shown to play a role in various cancers, including breast cancer. However, FABP5 and its role in triple negative breast cancer (TNBC) have not been studied. We show FABP5 protein expression correlates with TNBC, high grade tumors, and worse disease-free survival in a tissue microarray containing 423 breast cancer patient samples. High FABP5 expression significantly correlates with epidermal growth factor receptor (EGFR) expression in these samples. Decreased tumor growth and lung metastasis were observed in FABP5-/- mice othotopically injected with murine breast cancer cells. FABP5 loss in TNBC tumor cells inhibited motility and invasion. Mechanistic studies revealed that FABP5 knockdown in TNBC cells results in decreased EGFR expression and FABP5 is important for EGF-induced metastatic signaling. Loss of FABP5 leads to proteasomal targeting of EGFR. Our studies show that FABP5 has a role in both host and tumor cell during breast cancer progression. These findings suggest that FABP5 mediates its enhanced effect on TNBC metastasis, in part, through EGFR, by inhibiting EGFR proteasomal degradation. These studies show, for the first time, a correlation between FABP5 and EGFR in enhancing TNBC metastasis through a novel mechanism.
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