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Review
. 2020 Mar 27;40(3):BSR20193353.
doi: 10.1042/BSR20193353.

Wnt/β-catenin signaling as an emerging potential key pharmacological target in cholangiocarcinoma

Guo-Feng Zhang  1 , Ling Qiu  2 , Shu-Li Yang  3 , Jia-Cheng Wu  1 , Tong-Jun Liu  4
Affiliations
Free PMC article
Review

Wnt/β-catenin signaling as an emerging potential key pharmacological target in cholangiocarcinoma

Guo-Feng Zhang et al. Biosci Rep. .
Free PMC article

Abstract

Cholangiocarcinoma (CCA) is a fatal malignant tumor of biliary epithelial cells involving intra- or extra-hepatic bile ducts. The prognosis of CCA is generally poor due to its diagnosis at the late stages. The currently employed chemotherapeutic agents do not increase the survival rate in patients with unresectable CCA. Accordingly, there is a need to identify new therapeutic agents for the effective management of intra- and extra-hepatic CCA. Clinical as well as preclinical studies have suggested the key role of the activation of Wnt/β-catenin signaling pathway in the induction and progression of CCA. There is an up-regulation of different Wnt ligands including Wnt2, Wnt3, Wnt5, Wnt7 and Wnt10 along with redistribution of β-catenin (more expression in the nucleus and lesser on the cell surface due to nuclear translocation of β-catenin) in different types of malignant biliary tumors. Apart from the role of this pathway in the induction and progression of CCA, this pathway is also involved in inducing multidrug resistance by inducing the expression of P-glycoprotein efflux pump on the cancer cells. These deleterious effects of Wnt/β-catenin signaling are mediated in association with other signaling pathways involving microRNAs (miRNAs), PI3K/AKT/PTEN/GSK-3β, retinoic acid receptors (RARs), dickkopf-1 (DKK1), protein kinase A regulatory subunit 1 α (PRKAR1A/PKAI), (SLAP), liver kinase B1 (LKB1) and CXCR4. The selective inhibitors of Wnt/β-catenin signaling may be potentially employed to overcome multidrug-resistant, fatal CCA. The present review discusses the role of Wnt/β-catenin along with its relation with other signaling pathways in the induction and progression of CCA.

Keywords: Wnt; cholangiocarcinoma; macrophages; miRNA; β-catenin.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Representation of interrelationship between Wnt/β-catenin with other signaling pathways leading to the development of CCA
Figure 2
Figure 2. Representation of the interactions between miRNAs and Wnt/β-catenin signaling leading to the development and progression of CCA
See this image and copyright information in PMC

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