New cell signalling finding sheds light on inflammation behind liver cancer

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 specific proteins 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).

“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 National Defense Medical Center, Taiwan) and first author of the study.

Corresponding author, Prof Henning Walczak (UCL and University of Cologne) 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 Prof Nieves Peltzer (UCL, University of Cologne and University of Stuttgart)

Further information

• Research paper: LUBAC enables tumor-promoting LTβ receptor signaling by activating canonical NF-κB. Cell Death & Differentiation 
• University of Cologne
• Genome Editing Department, IBMG, University of Stuttgart
• Aragon Health Research Institute (IIS Aragon), Biomedical Research Centre of Aragon (CIBA)
• Prof Henning Walczak academic profile
• Prof Nieves Peltzer academic profile