New advances in the analysis of mechanisms during the development of hepatocellular carcinoma

Researchers from IDIBELL, CIC bioGUNE and CIBEREHD discover that a protein called NOX4, which was previously thought to cause cell death, can also help tumor growth.

The study published in the journal Redox Biology could open the door to new treatment options and personalized approaches for liver cancer patients.

Researchers from CIC bioGUNE - member of BRTA - have participated in a collaborative research project led by the TGF-Beta and Cancer group at IDIBELL. The team led by Dr. Isabel Fabregat, researcher at IDIBELL and CIBEREHD, has dissected the role of the NOX4 protein in the response to TGF-beta, one of the factors that controls the progression of hepatocellular carcinoma, the most common type of cancer of liver.

The study has shown that the NOX4 protein, initially considered a defender against TGF-beta-induced cancer cell growth, may have a less positive effect in some cases. It turns out that when NOX4 and TGF-beta levels are high in patients, their prognosis is not as good as expected. This suggests that, in certain contexts, NOX4 may also contribute to tumor growth. To understand this better, researchers delved into the role of NOX4 in response to TGF-beta and discovered that NOX4 is also involved in making cancer cells move and invade other tissues, all through changes in the internal structure of the cells.

Our findings provide deeper insight into how NOX4 and TGF-beta interact in liver cancer. This could open the door to new treatment options and personalized approaches for patients", says Dr. Fabregat. She continues: "NOX4 helps control tumor growth, but it is also necessary for cancer cells to move and they extend”.

The work has been carried out in the context of a collaboration within the CIBEREHD, with the Liver Disease Laboratory, led by Dr. Malu Martínez-Chantar at CIC bioGUNE, an international collaboration with the group of Dr. Gianluigi Giannelli (IRCCS Saverio De Bellis Research Hospital, Bari) and has had the support of the Spanish Association against Cancer (AECC) and the State Research Agency (MICINN).

The need to uncover the mechanisms behind malignancy in HCC is crucial for enhancing diagnosis, treatment, and prognosis. This article underscores the significance of NOX4's potential role in both inhibitory and pro-tumorigenic actions of TGF-beta within HCC cells”, highlights Dr. Martínez-Chantar.

Hepatocellular carcinoma is one of the deadliest malignancies worldwide due to its high recurrence rate, high metastatic potential, and drug resistance. For this reason, the results of this research are very valuable for a better understanding and eventually a more effective fight against this disease.

Reference: Rut Espinosa-Sotelo, Noel P Fusté, Irene Peñuelas-Haro, Ania Alay, Gabriel Pons, Xènia Almodóvar, Júlia Albaladejo, Ismael Sánchez-Vera, Ricard Bonilla-Amadeo, Francesco Dituri, Grazia Serino, Emilio Ramos, Teresa Serrano, Mariona Calvo, María Luz Martínez-Chantar, Gianluigi Giannelli, Esther Bertran, Isabel Fabregat. Redox Biol. DOI: 10.1016/j.redox.2023.102818

About CIC bioGUNE

The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.


The Consortium of Biomedical Network Research Centres (CIBER) is a public research consortium created on the initiative of the Instituto de Salud Carlos III / Carlos III Health Institute, of the Ministry of Science and Innovation, to further research of excellence in biomedicine and health sciences conducted within the National Health System and the Science and Technology System. The scientific programme of the CIBER is organised around 13 thematic areas of research, including the area of Liver Diseases (CIBEREHD) and Diabetes and Associated Metabolic Diseases (CIBERDEM).


The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research centre in which participate the Bellvitge University Hospital and the Viladecans Hospital, the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of l'Hospitalet de Llobregat. IDIBELL's research focuses are cancer, neurosciences, translational medicine and regenerative medicine.

About BRTA

BRTA is an alliance of 4 collaborative research centres (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 12 technology centres (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Lortek, Neiker, Tecnalia, Tekniker and Vicomtech) with the main objective of developing advanced technological solutions for the Basque corporate fabric.

With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three territories, the alliance seeks to promote collaboration between the research centres, strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness and outspreading the Basque scientific-technological capacity abroad.

BRTA has a workforce of 3,500 professionals, executes 22% of the Basque Country's R&D investment, registers an annual turnover of more than 300 million euros and generates 100 European and international patents per year.


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