The IT-LIVER European consortium unveils new TGF-beta functions in liver cancer


Recent research results from the TGF-beta and cancer research group at the Bellvitge Biomedical Research Institute (IDIBELL), within IT-Liver, a collaborative European action among several research groups led by Dr. Isabel Fabregat, provide a better understanding of the role of the TGF-beta cytokine in liver cancer. Their work, published in Cancer Letters, shows how the TGF-beta cytokine is able to modulate not only the migratory capacity of the hepatocellular carcinoma cell but also its capacity as a tumor initiator cell.

TFG-beta plays a dual role in cancer: at the beginning, it acts as a suppressor of tumors, but in advanced stages it becomes an enhancer. “So far we had deeply studied the relationship between the tumorigenic potential of TGF-beta and its ability to induce a process known as epithelial-mesenchymal transition, which favors the migration of cancer cells. The present work also shows that during that process TGF-beta could also modulate the tumor cell’s ability to behave as a tumor initiator, its stemness”, explains Dr. Isabel Fabregat, associate professor at the University of Barcelona and the last author of the paper.

“Tumoral cells entering the circulatory or lymphatic system must have migratory capacity to be able to move and invade other body areas, but at the same time they must also acquire some stemness so that they can metastasize and expand once they have reached their destination”, says the IDIBELL researcher. Epithelial-like cells can act as tumor-initiating cells, but have no migration capability; in contrast, mesenchymal cells have high migratory capacity.

“Curiously, the study shows that those cells with the greatest capacity as tumor initiators are not those of the mesenchymal type, but those that express an epithelial-mesenchyme intermediate phenotype, which would combine stemness with a greater migratory potential; this is the greatest innovation brought by our study”, adds Fabregat.

The IT-Liver consortium (Inhibiting TGF-β in liver diseases), which has made this study possible, is a Marie Curie (ITN) European initial training network led by IDIBELL. Over the last 4 years, IT-Liver has created a combined research and training program for both early-stage researchers and experienced researchers to better understand the molecular mechanisms of liver disease involving TGF-beta, in addition to providing in-depth comprehension of molecular liver cell biology and also enhancing skills in tech transfer activities (e.g. intellectual property management, valorization, entrepreneurship).

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