title: Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer cells through enhancing epidermal growth factor receptor stability.
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.
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Powell
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Mohd W
authors.initials: MW
authors.lastname: Nasser
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Helong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Wochna
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Tisch Cancer Institute, Mount Sinai School of Medicine, New York, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Shapiro
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Shilo
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ganju
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: C493412:FABP5 protein, human; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; C512478:EGFR protein, human; C541485:EGFR protein, mouse; D066246:ErbB Receptors
keywords: epidermal growth factor receptor; fatty acid binding protein 5; metastasis; protein degradation; triple negative breast cancer