Are connexins, pannexins and their (hemi)channels novel biomarkers and pharmacological targets in the prognosis and therapy of liver cancer? (Toekenning in het kader van bilaterale onderzoekssamenwerking met Brazilië)

Connexin and pannexin proteins are the building stones of hemichannels and channels, respectively, which are transmembrane pores that mediate paracrine cellular communication, in particular in pathological conditions. Belgian-Brazilian joint research over the past years showed altered expression of connexin43 and pannexin1 in acute and chronic liver disease as well as alleviation of the clinical manifestation of liver pathology upon pharmacological inhibition of their (hemi)channels. These findings suggest that connexins, pannexins and their (hemi)channels can serve as biomarkers and therapeutic targets in the hepatology field. The present Belgian-Brazilian project will investigate whether these findings can be extrapolated to liver cancer, which frequently is the end stage of chronic liver disease. Cell culture and animal models of liver cancer will be studied for expression of connexin43 and pannexin1. This will be complemented by testing of human liver cancer samples and linked to disease progression. Subsequently, connexin43 and pannexin1 (hemi)channels will be pharmacologically inhibited in the cell culture and animal models followed by investigation of clinical features of liver cancer. Overall, this project, by combining fundamental with translational research, is considered of clinical relevance, as it may introduce a novel strategy for the prognosis and treatment of liver cancer