A Network Map of Intracellular Alpha-Fetoprotein Signalling in Hepatocellular Carcinoma

Abstract

Alpha fetoprotein (AFP) is a glycoprotein of foetal origin belonging to the albumin protein family. Serum AFP is a long-conceived early-diagnostic biomarker for HCC with its elevated expression in different liver pathologies ranging from hepatitis viral infections to fibrosis, cirrhosis, and HCC. Beyond their utility as biomarkers, in support of its contribution to these clinical outcomes, the function of AFP as an immune suppressor and inducer of malignant transformation in HCC patients is well reported. Multiple reports show that AFP is secreted by hepatocytes, binds to its cognate receptor, AFP-receptor (AFPR), and exerts its actions. However, there is only limited information available in this context. There is an urgent need to gather more insight into the AFP signalling pathway and consider it a classical intracellular signalling pathway, among others. AFP is a highly potent intracellular molecule that has the potential to bind to many interactors like PTEN, Caspase, RAR, and so on. It has been shown that cellular AFP and secreted AFP have different roles in HCC pathophysiology, and a comprehensive map of the AFP signalling pathway is warranted for further theranostic applications.