Published online Sep 7, 2016. doi: 10.3748/wjg.v22.i33.7486
Peer-review started: March 28, 2016
First decision: May 12, 2016
Revised: June 7, 2016
Accepted: July 20, 2016
Article in press: July 20, 2016
Published online: September 7, 2016
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies in the world. Several signaling pathways, including the wingless/int-1 (Wnt) signaling pathway, have been shown to be commonly activated in HCC. The Wnt signaling pathway can be triggered via both catenin β1 (CTNNB1)-dependent (also known as “canonical”) and CTNNB1-independent (often referred to as “non-canonical”) pathways. Specifically, the canonical Wnt pathway is one of those most frequently reported in HCC. Aberrant regulation from three complexes (the cell-surface receptor complex, the cytoplasmic destruction complex and the nuclear CTNNB1/T-cell-specific transcription factor/lymphoid enhancer binding factor transcriptional complex) are all involved in HCC. Although the non-canonical Wnt pathway is rarely reported, two main non-canonical pathways, Wnt/planar cell polarity pathway and Wnt/Ca2+ pathway, participate in the regulation of hepatocarcinogenesis. Interestingly, the canonical Wnt pathway is antagonized by non-canonical Wnt signaling in HCC. Moreover, other signaling cascades have also been demonstrated to regulate the Wnt pathway through crosstalk in HCC pathogenesis. This review provides a perspective on the emerging evidence that the aberrant regulation of Wnt signaling is a critical mechanism for the development of HCC. Furthermore, crosstalk between different signaling pathways might be conducive to the development of novel molecular targets of HCC.
Core tip: The development of hepatocellular carcinoma (HCC) is regarded as a multistage process in which multiple genetic alterations are necessary. The wingless/int-1 (Wnt) pathway is a signaling mechanism that is frequently activated in HCC, especially the canonical Wnt pathway. Moreover, two main non-canonical pathways are also involved in the regulation of hepatocarcinogenesis. Interestingly, the non-canonical Wnt pathway could antagonize the canonical Wnt pathway in HCC. Crosstalk between other signaling pathways and the Wnt pathway has also been shown to promote tumorigenesis. This review highlights the details regarding the Wnt pathway in HCC, which might provide new potential targets for HCC prevention and therapy.