CIC bioGUNE identifies two key proteins that control the growth of paediatric hepatoblastoma cancer
A recent study published in the journal Hepatology reveals how two essential proteins influence the growth of childhood hepatoblastoma and provides new insights into its biology and possible future lines of research
A paper published in Hepatology presents new findings on the molecular mechanisms underlying hepatoblastoma, the most common liver cancer in children. The research identifies alterations in the NEDDylation pathway, particularly related to the enzyme NEDP1 and the protein CAND1, which contribute to tumour development and progression.
Hepatoblastoma is a rare paediatric tumour that affects approximately 1–2 children per million each year. Although current treatments have significantly improved survival, some patients experience relapse or resistance to chemotherapy. A better understanding of the biological mechanisms driving this disease could help refine future therapeutic strategies.
The study, led by Dr María Luz Martínez-Chantar (CIBERehd) at CIC bioGUNE, a member of BRTA, shows that hepatoblastoma tumours have reduced levels and activity of NEDP1, a protease that regulates NEDDylation, a post-translational modification process involved in protein regulation. This reduction is associated with increased NEDDylation and elevated levels of CAND1, a protein linked to more aggressive molecular subtypes and poorer clinical outcomes.
By analysing patient samples to validate the dysregulation of the NEDD8 pathway and using various preclinical models, including cell lines, patient-derived tumour xenografts and animal models, the research team observed that restoring NEDP1 activity reduced tumour growth, limited metastatic potential and altered the metabolism of cancer cells. In addition, high CAND1 expression was associated with adverse prognostic features and lower overall survival in patients.
‘Our results indicate that alterations in the NEDP1–CAND1 axis contribute to hepatoblastoma progression,’ explains Dr. Martínez-Chantar. ‘These findings improve our understanding of the molecular landscape of this tumour and suggest that the NEDDilation pathway could represent a potential area for future therapeutic exploration.’
Estefanía Zapata-Pavas, lead author of the study, adds: ‘We observed that NEDP1 acts as a tumour suppressor by regulating key proteins involved in cell proliferation and metabolism. When this regulatory balance is disrupted, tumour cells gain growth advantages.’
The study was conducted within the framework of collaborative initiatives supported by the Spanish Association Against Cancer (AECC) through the coordinated project PMEd4HB (Precision Medicine for Hepatoblastoma, reference PRYCO223102ARME), led and coordinated by the Germans Trias i Pujol Research Institute (IGTP). This consortium, with Dr. Carolina Armengol (IGTP) as principal investigator and leading expert in paediatric liver cancer, brings together other specialised groups in Spain, such as those led by Dr. Matias Avila (CIMA), Dr. José Juan García-Marín (USAL) and Dr. Pau Sancho -Bru (IDIBAPS), promoting a multidisciplinary approach aimed at accelerating the transfer of fundamental discoveries into clinically relevant advances for patients. Researchers Estefanía Zapata-Pavas and Marina Serrano-Macia have the support of the Cancer Association in Bizkaia.
This work provides valuable information about the mechanisms that regulate hepatoblastoma growth and how certain proteins can influence its aggressiveness. Although these are preclinical results, the study highlights the importance of researching cancer metabolism and provides a solid basis for exploring new strategies that could guide the development of more targeted and scientifically sound treatments in the future.
