2024-09-19 15:38:06
This new molecular pathway can also be observed in other cancer cells in addition to liver cancer, suggesting that it may be a non-specific protumorigenic entity.
In Spain, more than 6,500 new cases of liver cancer are diagnosed each year. Finding a molecular marker can be useful in predicting the progression of liver cancer. This is the result of research carried out by scientific teams at the University College London (UCL) Cancer Institute; University of Cologne; Health Research Center of Aragón, and University of Stuttgart.
These researchers have identified LUBAC (acronym for linear ubiquitin complex assemblylinear ubiquitin chain assembly complex) as an important factor for pro-tumorigenic lymphotoxin β receptor (LTβR) signaling.
This work, recently published in the journal Cell Death and Differentiationthat belongs to the group Creationhas important implications for understanding the molecular mechanisms of tumor growth that are vulnerable to injury, especially in liver cancer.
The LTβR receptor is well known for its role in the development and maturation of lymphoid tissues, and is important for the normal functioning of the immune system. However, its activation also favors the proliferation and growth of tumors by activating the flow of pro-inflammatory factors. Despite its importance, until now there is no detailed understanding of how LTβR signaling works.
Details of molecular activity
In this study, by Henning Walczak, Diego de Miguel and Nieves Peltzer, conducted by Yu-Guang Chen and collaborators, LUBAC has been discovered to be an important and previously unknown component of the LTβR signaling complex (LTβR-SC) . ).
They found that the linear ubiquitin chains generated by LUBAC facilitate the recruitment of several factors necessary to efficiently modulate LTβR signaling, cooperatively regulating the balance between canonical and non-canonical NF-κB. Thus, LUBAC is responsible for the generation of pro-inflammatory and pro-tumorigenic cytokines after LTβR activation through activation of the canonical NF-κB pathway.
According to the study, this device seems to be important for patients with liver cancer. In this sense, as stated by Yu-Guang Chen: “Based on our innovative biochemical findings on LTβR signaling, we performed a bioinformatics analysis indicating that the existence of high LTβR expression with high LUBAC expression is consistent with the prediction of not good in patients with liver cancer. “This demonstrates the clinical importance of LTβR and LUBAC central inflammatory signaling.”
On the other hand, the authors show that this newly described process can also be observed in other types of cancer cells in addition to liver cancer, suggesting that it may be a more general protumorigenic process. Walczak said that “in this study we redefined how LTβR signaling works and showed that it is important for the protumorigenic activation of NF-kB in many types of cancer.”
Potential biomarkers and therapeutic targets
De Miguel said himself in the same lines: “Although in our study we focused mainly on liver cancer, there may be similar mechanisms behind the development of other cancers known to be caused by inflammation. Future studies will reveal this. ” Finally, Nieves Peltzer showed the immediate clinical relevance of the results shown in the study: “Our findings have the potential to develop patient stratification criteria and therapeutic strategies targeting LUBAC activity. “
This discovery represents an important advance in our understanding of the molecular mechanisms of LTβR signaling and its role in cancer progression. Researchers hope that these insights will pave the way for new treatment methods to improve outcomes for patients with liver cancer. Rv LDB (SyM)
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