title: Role of C5b-9 complement complex and response gene to complement-32 (RGC-32) in cancer.
abstract: Complement system activation plays an important role in both innate and acquired immunity, with the activation of complement and the subsequent formation of C5b-9 terminal complement complex on cell membranes inducing target cell death. Recognition of this role for C5b-9 leads to the assumption that C5b-9 might play an antitumor role. However, sublytic C5b-9 induces cell cycle progression by activating signal transduction pathways and transcription factors in cancer cells, indicating a role in tumor promotion for this complement complex. The induction of the cell cycle by C5b-9 is dependent upon the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/FOXO1 and ERK1 pathways in a Gi protein-dependent manner. C5b-9 also induces response gene to complement (RGC)-32, a gene that plays a role in cell cycle promotion through activation of Akt and the CDC2 kinase. RGC-32 is expressed by tumor cells and plays a dual role in cancers, in that it has both a tumor suppressor role and tumor-promoting activity. Thus, through the activation of tumor cells, the C5b-9-mediated induction of the cell cycle plays an important role in tumor proliferation and oncogenesis.
authors.affiliation: Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Vlaicu
authors.forename: Cosmin A
authors.initials: CA
authors.lastname: Tegla
authors.forename: Cornelia D
authors.initials: CD
authors.lastname: Cudrici
authors.forename: Jacob
authors.initials: J
authors.lastname: Danoff
authors.forename: Hassan
authors.initials: H
authors.lastname: Madani
authors.forename: Adam
authors.initials: A
authors.lastname: Sugarman
authors.forename: Florin
authors.initials: F
authors.lastname: Niculescu
authors.forename: Petru A
authors.initials: PA
authors.lastname: Mircea
authors.forename: Violeta
authors.initials: V
authors.lastname: Rus
authors.forename: Horea
authors.initials: H
authors.lastname: Rus
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics*; D016923:Cell Death; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D020935:MAP Kinase Signaling System; D009124:Muscle Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D015938:Complement Membrane Attack Complex; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C115049:RGCC protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go