Hepatocellular carcinoma is one of the most common causes of cancer-related death
worldwide. Hepatocellular carcinoma development depends on the inhibition and activation
of multiple vital pathways, including the Wnt signaling pathway. The Wnt/β-catenin pathway
lies at the center of various signaling pathways that regulate embryonic development,
tissue homeostasis and cancers. Activation of the Wnt/β-catenin pathway has been observed
frequently in hepatocellular carcinoma. However, activating mutations in β-catenin, Axin
and Adenomatous Polyposis Coli only contribute to a portion of the Wnt signaling
hyper-activation observed in hepatocellular carcinoma. Therefore, besides mutations in the
canonical Wnt components, there must be additional atypical regulation or regulators
during Wnt signaling activation that promote liver carcinogenesis. In this mini-review, we
have tried to summarize some of these well-established factors and to highlight some
recently identified novel factors in the Wnt/β-catenin signaling pathway in hepatocellular
carcinoma.
Impact statement
Early recurrence of human hepatocellular carcinoma (HCC) is a frequent cause of poor
survival after potentially curative liver resection. Among the deregulated signaling
cascades in HCC, evidence indicates that alterations in the Wnt/β-catenin signaling
pathway play key roles in hepatocarcinogenesis. In this review, we summarize the
potential molecular mechanisms how the microtubule-associated Protein regulator of
cytokinesis 1 (PRC1), a direct Wnt signaling target previously identified in our
laboratory to be up-regulated in HCC, in promoting cancer proliferation, stemness,
metastasis and tumorigenesis through a complex regulatory circuitry of Wnt3a
activities.
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