title: CXCL13 mediates prostate cancer cell proliferation through JNK signalling and invasion through ERK activation.
abstract: OBJECTIVE
  The focus of this study was to determine the dedicator of cytokinesis 2 (DOCK2), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase-1 (JNK) and Akt signals involved in CXCL13-mediated prostate cancer (PCa) cell invasion and proliferation.
  
  
  METHODS
  Androgen-sensitive (LNCaP), hormone-refractory (PC3) cells and normal cells (RWPE-1) were used to determine CXCL13-mediated PCa cell invasion and proliferation. Immuno-blotting, fast activated cell-based (FACE) ELISA, caspase activity, cell invasion and proliferation assays were performed to ascertain some of the signalling events involved in PCa cell proliferation and invasion.
  
  
  RESULTS
  Unlike androgen-sensitive LNCaP cells, we report for the first time that the hormone-refractory cell line, PC3, expresses DOCK2. CXCL13-mediated LNCaP and PC3 cell invasion was regulated by Akt and ERK1/2 activation in a DOCK2-independent fashion. CXCL13 also promoted LNCaP cell proliferation in a JNK-dependent fashion even in the absence of DOCK2. In contrast, CXCL13 induced PC3 cell proliferation through JNK activation, which required DOCK2.
  
  
  CONCLUSIONS
  Our results show CXCL13-mediated PCa cell invasion requires Akt and ERK1/2 activation and suggests a new role for DOCK2 in proliferation of hormone-refractory CXCR5-positive PCa cells.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: El-Haibi
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.forename: P K
authors.initials: PK
authors.lastname: Sharma
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.forename: J W
authors.initials: JW
authors.lastname: Lillard
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054382:Chemokine CXCL13 / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D054380:Receptors, CXCR5 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; C402110:DOCK2 protein, human; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D054380:Receptors, CXCR5; D051058:Oncogene Protein v-akt; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3