Mitochondrial Dynamics and Liver Cancer.

Abstract

Simple SummaryHepatocellular carcinoma is a leading cause of cancer-related death worldwide. Major risk factors in liver cancer development include chronic hepatitis B or C virus, autoimmune hepatitis, diabetes mellitus, alcohol abuse, and several metabolic diseases, among others. Standard therapy shows low efficacy, and there is an urgent need for novel therapies. Recent data permit to propose that proteins that control mitochondrial morphology through changes in mitochondrial fusion or mitochondrial fission, confer susceptibility or resistance to the development of liver cancer in mouse models. Here, we review the data that suggest mitochondrial dynamics to be involved in the development of liver tumors.Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. Due to its rising incidence and limited therapeutic options, HCC has become a leading cause of cancer-related death worldwide, accounting for 85% of all deaths due to primary liver cancers. Standard therapy for advanced-stage HCC is based on anti-angiogenic drugs such as sorafenib and, more recently, lenvatinib and regorafenib as a second line of treatment. The identification of novel therapeutic strategies is urgently required. Mitochondrial dynamics describes a group of processes that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial morphology and distribution, and connectivity mediated by tethering and fusion/fission events. In recent years, mitochondrial dynamic processes have emerged as key processes in the maintenance of liver mitochondrial homeostasis. In addition, some data are accumulating on the role played by mitochondrial dynamics during cancer development, and specifically on how such dynamics act directly on tumor cells or indirectly on cells responsible for tumor aggression and defense. Here, we review the data that suggest mitochondrial dynamics to be involved in the development of liver tumors.