13 Dicembre 2024

Transglutaminase type 2 controls metabolic reprogramming in hepatocellular carcinoma

Mauro Piacentini, ordinario presso l’Università di Roma Tor Vergata, alle ore 15.00 terrà un seminario dal titolo "Transglutaminase type 2 controls metabolic reprogramming in hepatocellular carcinoma".

Il professor Piacentini è Direttore del Laboratorio di Biologia Cellulare dell’Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani di Roma ed è uno dei fondatori delle riviste “Cell Death and Differentiation” e “Cell Death & Disease” , per le quali opera come Receiving Editor e Section Editor dal 1994.

Ospita il professore Franco Salvatore

Abstract

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the fifth cause of cancer-related death. Sorafanib (a multikinases inhibitor) is the only FDA approved treatment for HCC, however a large number of patients develop resistance to this drug regime. Thus, the discovery of new effective drugs to treat HCC is absolutely needed. Transglutaminase 2 (TG2) is deregulated in several liver diseases that are characterized by unbalanced cellular adaptation to cell-autonomous or environmental stress, however its role in HCC is undefined. The results obtained in this study demonstrated a key role of TG2 in the development of HCC and even more important we have defined that cysteamine (a TG2 inhibitor approved by FDA and EMA) can drastically reduce the HCC development. In particular the ablation /inhibition of TG2 prevents the transformation of preneoplastic nodules into mature HCC associated with reduced inflammation and increased cell death. By using a combined RNA seq and metabolic approaches we found that the presence of TG2 favours the expression of PHGDH and PSAT expression, the key enzyme in the serine biosynthesis and one-carbon metabolism that are essential for tumor growth. In addition, we have defined some of the molecular mechanisms that are controlled by the enzyme and can represent a further target to develop new therapeutic approach for the treatment of this deadly tumor. All together these data indicate in TG2 a key player in the reprogramming of HCC metabolism typically occurring in HCC development.

About Mauro

Since 2000 full Professor of Cellular and Developmental Biology at University of Rome "Tor Vergata", Rome. Since 1998 Basic Research Director at the National Institute for Infectious Diseases IRCCS “Lazzaro Spallanzani” in Rome. Co-Founder and Editor-in-Chief of Cell Death & Disease and Senior Editor of Cell Death & Differentiation. Since 2018 is President of the National Research Committee the Ministry of Health. Prof Piacentini has been president of the European Cell Death Organization of which he has been one of the founders in 1992. His scientific interest (380 peer reviewed publications, H-index 100; Citations 72000) focuses on the molecular mechanisms regulating cell death and autophagy both under physiological and pathological conditions with particular regard to the biological role of Type 2 Transglutaminase. In addition, in 2007 the laboratory of Prof. Piacentini has discovered one of the essential members of the Beclin1 complex regulating autophagy, Ambra1. His scientific work has been published in prestigious journals such as: Nature, Science, Nature Cell Biology, Nature Medicine, PNAS, Developmental and Molecular Cell ecc. For these studies Prof. Piacentini has received in 2007 the prestigious “Descartes” award from the European Commission and in 2013 the Career award from The International Cell Death Society.