WNT/β-catenin signaling in the development of liver cancers

The WNT/β-catenin signaling pathway is a highly conserved and tightly controlled molecular mechanism that regulates embryonic development, cellular proliferation and differentiation. Of note, accumulating evidence has shown that the aberrant of WNT/β-catenin signaling promotes the development and/or progression of liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the two most prevalent primary liver tumours in adults. There are two different WNT signaling pathways have been identified, which were termed non-canonical and canonical pathways, the latter involving the activation of β-catenin. β-catenin, acting as an intracellular signal transducer in the WNT signaling pathway, is encoded by CTNNB1 and plays a critical role in tumorigenesis. In the past research, most liver tumors have mutations in genes encoding key components of the WNT/β-catenin signaling pathway. In addition, several of other signaling pathways also can crosswalk with β-catenin. In this review, we discuss the most relevant molecular mechanisms of action and regulation of WNT/β-catenin signaling in the development and pathophysiology of liver cancers, as well as in the development of therapeutics.