Speaker: Prof. Elisabetta Rovida, Molecular Oncology & Cell Signalling. Associate Professor University of Florence.

ERK5 is a member of the mitogen-activated protein kinase family (MAPK) whose functions in the liver are still being explored. Our group has long studied the role of ERK5 in liver pathophysiology, initially identifying its contribution to the development and progression of hepatocellular carcinoma and cholangiocarcinoma. More recently, we have extended our research to metabolic dysfunctionassociated steatotic liver disease (MASLD), broadening our understanding of the role of ERK5 in both primary liver cancers and metabolic liver disease. In the latter context, we investigate how ERK5 affects the hepatocyte response to lipotoxic stress. Studies in mice and hepatocyte models indicate that ERK5 helps maintain insulin sensitivity, in part by limiting oxidative stress and
mitochondrial dysfunction. Alongside this work, we continue to investigate how ERK5 interacts with pathways that support tumour cell survival and growth. In hepatocellular carcinoma, we have identified changes in EGFR signalling following ERK5 inhibition, while our studies in intrahepatic cholangiocarcinoma point to a role for ERK5 in the response to hypoxia. Together, these findings highlight the different functions of ERK5 across liver diseases and underscore the need to consider these differences when exploring ERK5 as a therapeutic target. The seminar will also consider whether targeting ERK5, alone or in combination with other pathways, could expand the currently
limited range of MAPK-targeted therapies for liver cancer.

Host: Dr. José Miguel Lizcano de Vega, Head of group Protein kinases in cancer research (VHIR)