Wnt/β-Catenin Signaling in Liver Cancers

Abstract

Liver cancer is among the leading global healthcare issues associated with high morbidity and mortality. Liver cancer consists of hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), hepatoblastoma (HB), and several other rare tumors. Progression has been witnessed in understanding the interactions between etiological as well as environmental factors and the host in the development of liver cancers. However, the pathogenesis remains poorly understood, hampering the design of rational strategies aiding in preventing liver cancers. Accumulating evidence demonstrates that aberrant activation of the Wnt/β-catenin signaling pathway plays an important role in the initiation and progression of HCC, CCA, and HB. Targeting Wnt/β-catenin signaling potentiates a novel avenue for liver cancer treatment, which may benefit from the development of numerous small-molecule inhibitors and biologic agents in this field. In this review, we discuss the interaction between various etiological factors and components of Wnt/β-catenin signaling early in the precancerous lesion and the acquired mechanisms to further enhance Wnt/β-catenin signaling to promote robust cancer formation at later stages. Additionally, we shed light on current relevant inhibitors tested in liver cancers and provide future perspectives for preclinical and clinical liver cancer studies.

Overexpression of Hepatocyte Chemerin-156 Lowers Tumor Burden in a Murine Model of Diethylnitrosamine-Induced Hepatocellular Carcinoma

“…The activation of β-catenin was commonly described in HCC [36]. Indeed, mRNA expression of this gene was non-significantly induced in HCC tissues of both mice groups (Figure 4g).…”

“…Protein levels of β-catenin were not higher in the tumors and did not differ between the groups (Figure 4h,i). Phosphorylation of β-catenin at S552 by Akt induces nuclear translocation of β-catenin [37], whereas phosphorylation of β-catenin at T41, S37, and S33 initiates its degradation [36]. Analysis of these phosphorylated β-catenins showed no difference between the mice with hepatic expression of chemerin-156 and controls ( Figure 4h,j,k).…”

Prognostic values of a novel multi-mRNA signature for predicting relapse of cholangiocarcinoma

“…Furthermore, PTTG1 was known as a transcription factor, which exerts transcriptional activity either by directly binding to DNA or by interacting with proteins, including p53 [34], and p53 was consistently an important cancer suppressor gene in cholangiocarcinoma [35]. Li et al found that cyclin A2 (CCNA2) promoted the EMT progression combined with MET/AKT/GSK-3b via the ROCK/AKT/ β-catenin pathway in bladder cancer [36], and aberrant activation of Wnt/β-catenin signaling was observed in the majority of CCA [37]. In colorectal cancer, knockdown of CCNA2 inhibited cancer growth by impairing cell cycle [38].…”

KCTD1 mutants in scalp‑ear‑nipple syndrome and AP‑2α P59A in Char syndrome reciprocally abrogate their interactions, but can regulate Wnt/β‑catenin signaling

“…The Wnt/β-catenin signaling pathway serves a key role in embryonic developmental processes (22,38,39) and carcinogenesis (40)(41)(42). Truncations in aPc are frequently found in familial adenomatous polyposis, a dominantly inherited disease characterized by polyps in the colon and rectum (43,44).…”