title: The phosphatase of regenerating liver 3 (PRL-3) promotes cell migration through Arf-activity-dependent stimulation of integrin α5 recycling.
abstract: The formation of metastasis is one of the most critical problems in oncology. The phosphatase of regenerating liver 3 (PRL-3) is a new target in colorectal cancer, mediating metastatic behavior through a promigratory function. However, detailed explanations for this effect have remained elusive. Here we show that PRL-3 interacts with the ADP-ribosylation factor 1 (Arf1). PRL-3 colocalizes with Arf1 in an endosomal compartment and associates with transmembrane proteins such as the transferrin receptor and α5 integrins. PRL-3 interacts with Arf1 through a distinct motif and regulates activation of Arf1. PRL-3-mediated migration depends on expression and activation of Arf1 and is sensitive to treatment with Brefeldin A. We also demonstrate that PRL-3 modulates recycling of α5 integrins and that its phosphatase activity as well as Arf activation and compartmentalization with Arf1 are required for this effect. In summary our data identify a new function for PRL-3 and show that Arf1 is a new PRL-3-dependent mediator of enhanced migration of cancer cells through enhanced recycling of matrix receptors.
authors.affiliation: Department of Internal Medicine I, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm,  Germany.
authors.forename: Denis
authors.initials: D
authors.lastname: Krndija
authors.forename: Christin
authors.initials: C
authors.lastname: Münzberg
authors.forename: Ulrike
authors.initials: U
authors.lastname: Maass
authors.forename: Margit
authors.initials: M
authors.lastname: Hafner
authors.forename: Guido
authors.initials: G
authors.lastname: Adler
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kestler
authors.forename: Thomas
authors.initials: T
authors.lastname: Seufferlein
authors.forename: Franz
authors.initials: F
authors.lastname: Oswald
authors.forename: Götz
authors.initials: G
authors.lastname: von Wichert
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: D039482:Integrin alpha5; D009363:Neoplasm Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases; D020558:GTP Phosphohydrolases; D020823:ADP-Ribosylation Factor 1