Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer cells through enhancing epidermal growth factor receptor stability.

Catherine A Powell,Konstantin Shilo,Xiaoli Zhang,Charles Shapiro,Helong Zhao,Jacob C Wochna,Ramesh K Ganju,Mohd W Nasser

doi:10.18632/oncotarget.3442

Catherine A Powell, Konstantin Shilo + Show 6 more

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https://doi.org/10.18632/oncotarget.3442

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Abstract

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.

Highlights

Fatty acid binding protein 5 (FABP5) is a member of the intracellular lipid binding protein family that bind long chain fatty acids and transport them throughout the cell
FABP5 is expressed in triple negative breast cancer and associates with worse prognosis
We observed high FABP5 protein expression significantly correlates with high grade tumors, triple negative breast cancer (TNBC) status (Fig. 1A-C, P=0.0036 and P

Summary

Introduction

Fatty acid binding protein 5 (FABP5) is a member of the intracellular lipid binding protein family that bind long chain fatty acids and transport them throughout the cell. FABP5 ( epidermal FABP, keratinocyte FABP, psoriasis-associated FABP, and mal1), was first identified in psoriatic lesions, and further characterized in the epidermis [1]. It plays a role in lipid signaling by binding to and shuttling long chain fatty acids and other hydrophobic ligands through the cytoplasm. FABP5 has been shown to play a role in HER2, a member of the epidermal growth factor receptor family, tumorigenesis [10]. FABP5 has been previously identified as being protumorigenic in retinoic acid signaling in triple negative breast cancer (TNBC) patients [11]. It was shown that FABP5 mRNA is expressed in TNBC patient www.impactjournals.com/oncotarget samples and predicts worse prognosis, a detailed analysis of its protein expression and especially its correlation with EGFR has not been extensively studied in breast cancer, especially TNBC

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