title: Exogenous FABP4 increases breast cancer cell proliferation and activates the expression of fatty acid transport proteins.
abstract: Adipose tissue plays an important role in tumor progression, because it provides nutrients and adipokines to proliferating cells. Fatty acid binding protein 4 (FABP4) is a key adipokine for fatty acid transport. In metabolic pathologies, plasma levels of FABP4 are increased. However, the role of this circulating protein is unknown. Recent studies have demonstrated that FABP4 might have a role in tumor progression, but the molecular mechanisms involved are still unclear. In this study, we analysed the role of eFABP4 (exogenous FABP4) in breast cancer progression. MCF-7 and MDA-MB-231 breast cancer cells did not express substantial levels of FABP4 protein, but intracellular FABP4 levels increased after eFABP4 incubation. Moreover, eFABP4 enhanced the proliferation of these breast cancer cells but did not have any effect on MCF-7 and MDA-MB-231 cell migration. Additionally, eFABP4 induced the AKT and MAPK signaling cascades in breast cancer cells, and the inhibition of these pathways reduced the eFBAP4-mediated cell proliferation. Interestingly, eFABP4 treatment in MCF-7 cells increased levels of the transcription factor FoxM1 and the fatty acid transport proteins CD36 and FABP5. In summary, we showed that eFABP4 plays a key role in tumor proliferation and activates the expression of fatty acid transport proteins in MCF-7 breast cancer cells. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Institut d'Investigació Sanitària Pere Virgili (IISPV), Centre d'R+D+I en Nutrició i Salut. Avda. de la Universitat, Reus, Spain.|Research Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, carrer Sant Llorenç, Reus, Spain.|Oncology Research Group, "Sant Joan" University Hospital, Oncology Institute of Southern Catalonia (IOCS), Av. del Dr. Josep Laporte, Reus, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Guaita-Esteruelas
authors.affiliation: Institut d'Investigació Sanitària Pere Virgili (IISPV), Centre d'R+D+I en Nutrició i Salut. Avda. de la Universitat, Reus, Spain.|Research Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, carrer Sant Llorenç, Reus, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Bosquet
authors.affiliation: Research Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, carrer Sant Llorenç, Reus, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Saavedra
authors.affiliation: Oncology Research Group, "Sant Joan" University Hospital, Oncology Institute of Southern Catalonia (IOCS), Av. del Dr. Josep Laporte, Reus, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Gumà
authors.affiliation: Research Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, carrer Sant Llorenç, Reus, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: Girona
authors.affiliation: Department of Surgery and Cancer, Imperial Centre for Translational and Experimental Medicine (ICTEM), Imperial College London, London W12 0NN, United Kingdom.
authors.forename: Eric W-F
authors.initials: EW
authors.lastname: Lam
authors.affiliation: Oncology Research Group, "Sant Joan" University Hospital, Oncology Institute of Southern Catalonia (IOCS), Av. del Dr. Josep Laporte, Reus, Spain.
authors.forename: Kepa
authors.initials: K
authors.lastname: Amillano
authors.affiliation: Oncology Research Group, "Sant Joan" University Hospital, Oncology Institute of Southern Catalonia (IOCS), Av. del Dr. Josep Laporte, Reus, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Borràs
authors.affiliation: Research Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, carrer Sant Llorenç, Reus, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Masana
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D050612:Fatty Acid Transport Proteins / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C493410:FABP4 protein, human; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D051057:Proto-Oncogene Proteins c-akt
keywords: cancer progression; cell biology; lipid chaperones; lipid metabolism; metabolic pathways