JournalFrontiers in Immunology
PublisherFrontiers Media S.A.
MetadataShow full item record
AbstractThe complement system represents an effective arsenal of innate immunity as well as an interface between innate and adaptive immunity. Activation of the complement system culminates with the assembly of the C5b-9 terminal complement complex on cell membranes, inducing target cell lysis. Translation of this sequence of events into a malignant setting has traditionally afforded C5b-9 a strict antitumoral role, in synergy with antibody-dependent tumor cytolysis. However, in recent decades, a plethora of evidence has revised this view, highlighting the tumor-promoting properties of C5b-9. Sublytic C5b-9 induces cell cycle progression by activating signal transduction pathways (e.g., Gi protein/ phosphatidylinositol 3-kinase (PI3K)/Akt kinase and Ras/Raf1/ERK1) and modulating the activation of cancer-related transcription factors, while shielding malignant cells from apoptosis. C5b-9 also induces Response Gene to Complement (RGC)-32, a gene that contributes to cell cycle regulation by activating the Akt and CDC2 kinases. RGC-32 is expressed by tumor cells and plays a dual role in cancer, functioning as either a tumor promoter by endorsing malignancy initiation, progression, invasion, metastasis, and angiogenesis, or as a tumor suppressor. In this review, we present recent data describing the versatile, multifaceted roles of C5b-9 and its effector, RGC-32, in cancer. Copyright Copyright 2019 Vlaicu, Tatomir, Rus and Rus.
SponsorsThis work was supported in part by a Veterans Administration Merit Award I01BX001458 (to HR) and by an RO1 NS42011 grant (to HR).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85067103364&doi=10.3389%2ffimmu.2019.01054&partnerID=40&md5=a9df677b10c3c95a2ed418a7c1ee8cde; http://hdl.handle.net/10713/10754
- Role of C5b-9 complement complex and response gene to complement-32 (RGC-32) in cancer.
- Authors: Vlaicu SI, Tegla CA, Cudrici CD, Danoff J, Madani H, Sugarman A, Niculescu F, Mircea PA, Rus V, Rus H
- Issue date: 2013 May
- Membrane attack by complement: the assembly and biology of terminal complement complexes.
- Authors: Tegla CA, Cudrici C, Patel S, Trippe R 3rd, Rus V, Niculescu F, Rus H
- Issue date: 2011 Oct
- Response gene to complement 32 is required for C5b-9 induced cell cycle activation in endothelial cells.
- Authors: Fosbrink M, Cudrici C, Tegla CA, Soloviova K, Ito T, Vlaicu S, Rus V, Niculescu F, Rus H
- Issue date: 2009 Apr
- Sublytic C5b-9 induces proliferation of glomerular mesangial cells via ERK5/MZF1/RGC-32 axis activated by FBXO28-TRAF6 complex.
- Authors: Yu T, Wang L, Zhao C, Qian B, Yao C, He F, Zhu Y, Cai M, Li M, Zhao D, Zhang J, Wang Y, Qiu W
- Issue date: 2019 Aug
- RGC-32 is expressed in the human atherosclerotic arterial wall: Role in C5b-9-induced cell proliferation and migration.
- Authors: Vlaicu SI, Tatomir A, Boodhoo D, Ito T, Fosbrink M, Cudrici C, Mekala AP, Ciriello J, Crişan D, Boţan E, Rus V, Rus H
- Issue date: 2016 Oct