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In the study, published in Cell Death & Differentiation, scientists focused on a receptor in the body called the lymphotoxin beta receptor (LTβR). This receptor is essential for building parts of the immune system, but it can also help promote cancer growth by causing inflammation. While inflammation is a vital part of the body’s immune response, excessive and prolonged inflammation can lead to multiple health problems.
The research team investigated the biology underpinning the action of LTβR and found that the protein complex LUBAC plays a crucial role in regulating how LTβR sends signals within cells by influencing a key signalling molecule called NF-κB. LUBAC essentially amplifies the pathway that promotes inflammation and suppresses the one that doesn't, leading to the production of cytokines that can help tumours grow and spread. According to the study, this mechanism appears to be particularly relevant for liver cancer but “the same biology may be behind the development of several other cancers known to be driven by inflammation,” says study author Dr. Diego de Miguel (UCL, University of Cologne and Aragon Health Research Institute (IIS Aragon).
“Based on our groundbreaking findings on LTβR signalling, we conducted a bioinformatic analysis which indicates that high levels of both LTβR and LUBAC, correlates with poor prognosis in liver cancer patients. This highlights the clinical significance of LUBAC-mediated inflammatory LTβR signalling,” says Yu-Guang Chen, PhD student (UCL Cancer Institute) and first author of the study.
Corresponding author, CECAD Professor Henning Walczak (University of Cologne and UCL) comments: “In this study we redefine how LTβ-Receptor signalling works and show that it is decisive for pro-tumourigenic NF-kB activation across several cancers.”
“This discovery represents a significant advancement in our understanding of the molecular underpinnings of LTβR signalling and its role in cancer progression. We are optimistic that these insights could pave the way for novel therapeutic approaches to improve outcomes for liver cancer patients,” concludes study author Professor Nieves Peltzer (University of Cologne, UCL and University of Stuttgart)
Publication Link:
https://www.nature.com/articles/s41418-024-01355-w
Useul Links:
https://www.cecad.uni-koeln.de/research/principal-investigators/full-members/henning-walczak
https://www.cecad.uni-koeln.de/research/principal-investigators/associated-members/m-de-las-nieves-peltzer
https://biochemie-med.uni-koeln.de/aktuelles-veranstaltungen#c171045