Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Complement membrane attack and tumorigenesis: a systems biology approach

Towner, Laurence D., Wheat, Richard A., Hughes, Timothy R. ORCID: and Morgan, B. Paul ORCID: 2016. Complement membrane attack and tumorigenesis: a systems biology approach. Journal of Biological Chemistry 291 (29) , pp. 14927-14938. 10.1074/jbc.M115.708446

[thumbnail of 1-s2.0-S0021925820412426-main.pdf]
PDF - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (3MB) | Preview


Tumor development driven by inflammation is now an established phenomenon, but the role that complement plays remains uncertain. Recent evidence has suggested that various components of the complement (C) cascade may influence tumor development in disparate ways; however, little attention has been paid to that of the membrane attack complex (MAC). This is despite abundant evidence documenting the effects of this complex on cell behavior, including cell activation, protection from/induction of apoptosis, release of inflammatory cytokines, growth factors, and ECM components and regulators, and the triggering of the NLRP3 inflammasome. Here we present a novel approach to this issue by using global gene expression studies in conjunction with a systems biology analysis. Using network analysis of MAC-responsive expression changes, we demonstrate a cluster of co-regulated genes known to have impact in the extracellular space and on the supporting stroma and with well characterized tumor-promoting roles. Network analysis highlighted the central role for EGF receptor activation in mediating the observed responses to MAC exposure. Overall, the study sheds light on the mechanisms by which sublytic MAC causes tumor cell responses and exposes a gene expression signature that implicates MAC as a driver of tumor progression. These findings have implications for understanding of the roles of complement and the MAC in tumor development and progression, which in turn will inform future therapeutic strategies in cancer.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Uncontrolled Keywords: cancer complement, inflammation, systems biology, tumor metastasis
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 0021-9258
Funders: Cardiff University
Date of First Compliant Deposit: 10 June 2020
Date of Acceptance: 19 May 2016
Last Modified: 05 May 2023 08:52

Citation Data

Cited 17 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics