title: Repulsive guidance molecules, novel bone morphogenetic protein co-receptors,             are key regulators of the growth and aggressiveness of prostate cancer cells.
abstract: Repulsive guidance molecule (RGM) family members RGMA, RGMB and RGMC are             GPI-linked membrane proteins recently identified as co-receptor of bone morphogenetic             proteins (BMPs). BMPs are a group of proteins enriched in bone and play important             roles in prostate cancer. The current study aimed to investigate roles played             by RGMs in prostate cancer. Expression of RGMs was examined in prostate cancer             cell lines and prostate cancer tissues using RT-PCR and immunohistochemical staining.             Knockdown of each RGM in prostate cancer cells was performed using the respective             anti-RGMA, RGMB and RGMC transgenes. A variety of in vitro function tests were             employed to analyze the influence on cancer cell functions by RGM knockdown. The             implications of RGM knockdown in BMP signalling were also examined using both             Western blot and real-time quantitative PCR. Knockdown of RGMA had no effect on             cell growth, migration and invasion, but promoted cell-matrix adhesion. Knockdown             of RGMB and RGMC increased growth and adhesion, but only RGMB knockdown increased             capacities of migration and invasion in PC-3 cells. Further investigations showed             an increase in Smad-3 activation and reduced levels of Smad-1 in PC-3 cells by             RGMB and RGMC knockdown, and also an up-regulation of ID1, a BMP target gene particularly             in exposure to BMP7. RGMs play inhibitory roles in prostate cancer by suppressing             cell growth, adhesion, migration and invasion. RGMs can coordinate Smad-dependent             signalling of BMPs in prostate cancer cells.
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff University                     School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Howard G
authors.initials: HG
authors.lastname: Kynaston
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism*; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C522183:RGMA protein, human; C560433:RGMB protein, human; C497399:SMAD1 protein, human; C497790:SMAD3 protein, human; D051898:Smad1 Protein; D051900:Smad3 Protein; D052004:Bone Morphogenetic Protein Receptors