Abstract P1-07-35: Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer

Abstract

Abstract Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has a poor prognosis for patients, not only due to its aggressive nature, but also due to the lack of effective therapeutic strategies. High mortality is associated with metastasis of the primary TNBC. We analyzed the role of fatty acid binding protein 5 (FABP5), an intracellular fatty acid transport protein, in aggressive breast cancers, especially TNBC. FABP5 expression was analyzed in a tumor microarray (TMA) containing 423 breast cancer patient samples and found that FABP5 expression is associated with tumor grade, triple negative status, and disease-free survival. Next, a mechanistic approach was taken and found that FABP5 knockdown TNBC cell lines express lesser EGFR protein compared to control, and upon EGFR activation express less phospho-FAK and phospho-Pyk2. We found that EGFR was not down regulated at the transcriptional level in FABP5 knockout cells. Further analysis indicated the role for Cbl, an E3 ubiquitin-protein ligase, as a potential mechanistic target for the down-regulation of EGFR protein in FABP5 knockdown cell lines. EGFR is over-expressed in aggressive breast cancers, especially TNBC. Though EGFR is highly expressed in aggressive subtypes of breast cancer, targeted therapeutic strategies have not been successful in clinic. EGFR has been shown to be involved in distant metastasis in aggressive breast cancers. We found a correlation between FABP5 and EGFR expression and metastasis-free survival using publically available datasets from The Cancer Genome Atlas. We next studied the functional consequence of FABP5 knockdown in TNBC cell lines. We showed that EGF-induced FABP5 knockdown cells migrated less compared to control. Additionally, FABP5 knockdown cells were significantly less able to migrate into a wound in response to EGF stimulation. EGF-induced cell attachment of FABP5 knockdown cells is significantly decreased compared to control. Our findings suggest FABP5 modulates metastatic potential of TNBC through alterations in EGFR expression and downstream migratory signaling molecules. Citation Format: Catherine A Powell, Mohd W Nasser, Jacob C Wochna, Konstantin Shilo, Xiaoli Zhang, Ramesh K Ganju. Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-35.