Liver Cancer: Decoding Tumor Development Pathway

Liver cancer: Molecular signalling pathway of tumour development decoded: As a malignant disease of the liver cells, hepatocellular carcinoma (HCC) is one of the main causes of cancer-related deaths.

While the treatment options for this aggressive type of cancer remain limited, the incidence is increasing. A research team led by Latifa Bakiri and Erwin Wagner from MedUni Vienna’s Clinical Institute for Laboratory Medicine has now described a molecular signalling pathway that plays a key role in the development of liver cancer, thereby identifying a potential new starting point for the development of therapeutic treatments. The results of the study have just been published in the journal “Proceedings of the National Academy of Sciences” (PNAS).

In their research, the international team led by MedUni Vienna, built on earlier study results that had suggested the involvement of certain transcription factors (c-Fos and c-Jun) in the development of hepatocellular carcinomas. Transcription factors are proteins involved in numerous cellular processes, including the control of genes associated with the development of HCC. To advance these findings, the scientists developed a new mouse model.

The experiments carried out with these proteins showed that the combination with previously unexplored (Fra) proteins in this context triggers the cascade of tumour formation. Specifically, this involves the interaction between c-Jun and Fra-2, which the studies showed to be essential in the development of liver cancer. “It is remarkable that we were able to reverse tumour growth by switching off the protein combination of c-Jun and Fra-2,” reports the head of the study Erwin Wagner.

The study also showed that tumour growth can be stopped by blocking a specific gene (c-Myc). “Accordingly, our research results suggest that the molecular signalling pathway we have identified represents a promising starting point for further research into HCC and the development of new therapeutic measures,” concludes first author Latifa Bakiri.

Hepatocellular carcinoma is an aggressive tumour with rapid progression and limited therapeutic options. Even though the incidence has increased significantly in Western countries in recent decades, this type of cancer is still comparatively rare. However, due to its poor prognosis, HCC is one of the most common causes of cancer-related deaths. HCC occurs in particular in the context of advanced liver disease (cirrhosis, chronic hepatitis B) and is often only diagnosed at a late stage.

Publication: Proceedings of the National Academy of Sciences (PNAS)

Liver cancer development driven by the AP-1/c-Jun~Fra-2 dimer through c-Myc

Latifa Bakiri, Sebastian C. Hasenfuss, Ana Guío-Carrión, Martin K. Thomsen, Peter Hasselblatt and Erwin F. Wagner

https://doi.org/10.1073/pnas.2404188121