title: Copper chaperone Atox1 plays role in breast cancer cell migration.
abstract: Copper (Cu) is an essential transition metal ion required as cofactor in many key enzymes. After cell uptake of Cu, the metal is transported by the cytoplasmic Cu chaperone Atox1 to P1B-type ATPases in the Golgi network for incorporation into Cu-dependent enzymes in the secretory path. Cu is vital for many steps of cancer progression and Atox1 was recently suggested to have additional functionality as a nuclear transcription factor. We here investigated the expression level, cellular localization and role in cell migration of Atox1 in an aggressive breast cancer cell line upon combining immunostaining, microscopy and a wound healing assay. We made the unexpected discovery that Atox1 accumulates at lamellipodia borders of migrating cancer cells and Atox1 silencing resulted in migration defects as evidenced from reduced wound closure. Therefore, we have discovered an unknown role of the Cu chaperone Atox1 in breast cancer cell migration.
authors.affiliation: Department Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Blockhuys
authors.affiliation: Department Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden. Electronic address: pernilla.wittung@chalmers.se.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wittung-Stafshede
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D001692:Biological Transport; D001943:Breast Neoplasms / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D003300:Copper / Q000737:chemistry*; D000079922:Copper Transport Proteins; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D056511:Metallochaperones / Q000378:metabolism*; D008958:Models, Molecular; D018832:Molecular Chaperones; D011554:Pseudopodia / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C474500:ATOX1 protein, human; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D018832:Molecular Chaperones; D003300:Copper; D000251:Adenosine Triphosphatases
keywords: Atox1; Breast cancer; Copper transporter; Lamellipodia; Migration