Investigation of the functional role and therapeutic potential of Pannexin1 channels in Hepatocellular Carcinoma: a translational approach

Abstract

Hepatocellular Carcinoma (HCC) is the most common malignant neoplasm in the liver, of which ~ 90% of cases arise in patients with chronic liver diseases. The diagnosis of HCC is usually late, a stage in which it is highly refractory to conventional treatments, resulting in high rates of morbidity and mortality. Therefore, an immediate search for new biomarkers and therapeutic approaches for human HCC is necessary. Pannexin1 (Panx1) is a transmembrane protein that forms communication channels between intra- and extracellular environment. Previous knowledge highlights the participation of Panx1 channels, especially in stimuli of a pathological nature, acting mainly in the activation of the inflammasome and recruitment of inflammatory cells. In the context of liver disease, the ablation or blockade of Panx1 channels in murine models of acute and chronic liver diseases showed a significant reduction in the inflammatory response and, consequently, an improvement in its clinical and pathological manifestations. Thereby, the investigation of the functional role of Panx1 channels in HCC becomes an important tool for the search for new biomarkers and therapeutic targets. For this purpose, the participation of Panx1 channels in hepatocarcinogenesis will be investigated in genetically modified mice. Furthermore, the evaluation as a potential therapeutic target will be carried out by the inhibition of these channels by the use of mimetic peptides in HCC cells, implanted in murine models of ectopic and syngeneic xenograft orthotopic. The findings of this study will be relevant for obtaining the necessary information for the development of biomarkers and therapeutic targets for human HCC. (AU)