Targeting Wnt/β-catenin pathway in hepatocellular carcinoma treatment

Abstract

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug resistance, tumor progression, and metastasis. A great effort in developing selective drugs to target components of the β-catenin pathway with anticancer activity is underway but only a few of them have reached phase I clinical trials. We aim to review the role of β-catenin pathway on hepatocarcinogenesis and liver cancer stem cell maintenance. We also evaluated the use of small molecules targeting the Wnt/β-catenin pathway with potential application for treatment of HCC.

Hypoxic microenvironment promotes proliferation and invasion of non-small cell lung cancer A549 Cells through Wnt/β-catenin signaling pathway

“…Furthermore, hypoxic microenvironment will affect cell proliferation, angiogenesis, invasion and metastasis of tumors [9][10][11]. Studies have shown that Wnt/β-catenin signaling pathway is involved in the proliferation, differentiation, metastasis and invasion of tumor cells [12,13], but no literature has reported the effect of Wnt/β-catenin signaling pathway on the proliferation, invasion and metastasis of NSCLC A549 cells under the hypoxic environment. Thus, in this study, we aimed to investigate the potential mechanism of Wnt/β-catenin signaling pathway through discovering the effects of Wnt/β-catenin signaling pathway on NSCLC A549 cell proliferation and invasion under the hypoxic microenvironment in an in-vitro experiment.…”

MicroRNA-197 Promotes Metastasis of Hepatocellular Carcinoma by Activating Wnt/β-Catenin Signaling

“…Wnt/β-catenin signaling activation is commonly activated in a wide variety of cancers [10,12], including HCC [13,14]. The mechanism of β-catenin activation in HCC involves mutations of the β-catenin gene,whichare noted in around 19% of all cases [48,49].…”

Forced expression of Wnt antagonists sFRP1 and WIF1 sensitizes chronic myeloid leukemia cells to tyrosine kinase inhibitors

“…Silencing of these genes via hypermethylation of their promoters has been shown to be part of the pathogenesis in a plethora of human malignancies. [1][2][3][4][5][6] Aberrant regulation of the Wnt signaling pathway is known to play a role in tumorigenesis and maintenance of cancer stem cells. 3,4,28 The Wnt pathway can be activated aberrantly not only by mutations of genes functioning in Wnt signaling such as APC and CTNNB1 but also by dysregulation of secreted antagonists.…”

“…[1][2][3][4][5][6] Wnt/β-catenin signaling has pivotal roles both in early developmental stages and in tissue maintenance of adults. The pathway operates by regulating specific genes that function in cell fate, proliferation, polarity, migration, and differentiation.…”