title: Superoxide Dismutase 1 Regulation of CXCR4-Mediated Signaling in Prostate Cancer Cells is Dependent on Cellular Oxidative State.
abstract: OBJECTIVE
  CXCL12, acting via one of its G protein-coupled receptors, CXCR4, is a chemoattractant for a broad range of cell types, including several types of cancer cells. Elevated expression of CXCR4, and its ligand CXCL12, play important roles in promoting cancer metastasis. Cancer cells have the potential for rapid and unlimited growth in an area that may have restricted blood supply, as oxidative stress is a common feature of solid tumors. Recent studies have reported that enhanced expression of cytosolic superoxide dismutase (SOD1), a critical enzyme responsible for regulation of superoxide radicals, may increase the aggressive and invasive potential of malignant cells in some cancers.
  
  
  METHODS
  We used a variety of biochemical approaches and a prostate cancer cell line to study the effects of SOD1 on CXCR4 signaling.
  
  
  RESULTS
  Here, we report a direct interaction between SOD1 and CXCR4. We showed that SOD1 interacts directly with the first intracellular loop (ICL1) of CXCR4 and that the CXCL12/CXCR4-mediated regulation of AKT activation, apoptosis and cell migration in prostate cancer (PCa) cells is differentially modulated under normal versus hypoxic conditions when SOD1 is present.
  
  
  CONCLUSIONS
  This study highlights a potential new regulatory mechanism by which a sensor of the oxidative environment could directly regulate signal transduction of a receptor involved in cancer cell survival and migration.
authors.forename: Brent
authors.initials: B
authors.lastname: Young
authors.forename: Chad
authors.initials: C
authors.lastname: Purcell
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Kuang
authors.forename: Nicholle
authors.initials: N
authors.lastname: Charette
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Dupré
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000502:physiology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; C000606290:SOD1 protein, human; D005047:Etoposide; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1