Date
2019Journal
Frontiers in ImmunologyPublisher
Frontiers Media S.A.Type
Article
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The 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.Sponsors
This 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 item
https://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/10713/10754ae974a485f413a2113503eed53cd6c53
10.3389/fimmu.2019.01054
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