Epithelial-Mesenchymal Transition in Liver Fluke-Induced Cholangiocarcinoma

Simple Summary Parasitic infection remains a health threat in many countries. Liver flukes, parasitic flatworms endemic to southeast and east Asia, cause bile duct inflammation and are major risk factors of bile duct cancer (cholangiocarcinoma). As the only group of eukaryotic organisms listed as carcinogens, liver flukes can increase cholangiocarcinoma incidence by 100-fold in some parts of Thailand. How they interact with bile duct epithelial cells during tumor initiation and progression is unknown. In this review, we summarize molecular and cellular evidence linking liver fluke-associated cholangiocarcinoma with mis-regulation of epithelial-mesenchymal transition (EMT), a multicellular morphogenetic process known to be involved in many normal and pathological settings, including cancer. EMT markers and regulators can potentially be used to facilitate cholangiocarcinoma diagnosis and treatment. Cholangiocarcinoma (CCA) is the second most common type of hepatic cancer. In east and southeast Asia, intrahepatic CCA is caused predominantly by infection of Opisthorchis viverrini and Clonorchis sinensis, two species of parasitic liver flukes. In this review, we present molecular evidence that liver fluke-associated CCAs have enhanced features of epithelial-mesenchymal transition (EMT) in bile duct epithelial cells (cholangiocytes) and that some of those features are associated with mis-regulation at the epigenetic level. We hypothesize that both direct and indirect mechanisms underlie parasitic infection-induced EMT in CCA.

Automated summary

This review summarizes the mechanisms of parasitic infection in the pathogenesis of bile duct cancer, focusing on the effects of epithelial-mesenchymal transition (EMT) in bile duct epithelial cells and its association with epigenetic dysregulation. It suggests that both direct and indirect mechanisms underlie the parasitic infection-induced EMT in cholangiocarcinoma (CCA).