Wnt-β-catenin Signaling Pathway, the Achilles' Heels of Cancer Multidrug Resistance

Morteza Ghandadi; Reza Valadan; Hamidreza Mohammadi; Javad Akhtari; Shabanali Khodashenas; Sorour Ashari

doi:10.2174/1381612825666191112142943

Wnt-β-catenin Signaling Pathway, the Achilles' Heels of Cancer Multidrug Resistance

Curr Pharm Des. 2019;25(39):4192-4207. doi: 10.2174/1381612825666191112142943.

Authors

Morteza Ghandadi^{1

2}, Reza Valadan^{3

4}, Hamidreza Mohammadi^{1

5}, Javad Akhtari^{3

6}, Shabanali Khodashenas⁷, Sorour Ashari^{1

5}

Affiliations

¹ Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
² Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
³ Molecular and Cell Biology Research Center (MCBRC), Faculty of Medicine, Mazandaran University of Medical Sciences, Sari 48157-33971, Iran.
⁴ Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari 48157-33971, Iran.
⁵ Department of toxicology and pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
⁶ Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
⁷ Department of Medical Biotechnology, Faculty of Medical Sciences, Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

PMID: 31721699
DOI: 10.2174/1381612825666191112142943

Abstract

Background: Most of the anticancer chemotherapies are hampered via the development of multidrug resistance (MDR), which is the resistance of tumor cells against cytotoxic effects of multiple chemotherapeutic agents. Overexpression and/or over-activation of ATP-dependent drug efflux transporters is a key mechanism underlying MDR development. Moreover, enhancement of drug metabolism, changes in drug targets and aberrant activation of the main signaling pathways, including Wnt, Akt and NF-κB are also responsible for MDR.

Methods: In this study, we have reviewed the roles of Wnt signaling in MDR as well as its potential therapeutic significance. Pubmed and Scopus have been searched using Wnt, β-catenin, cancer, MDR and multidrug resistance as keywords. The last search was done in March 2019. Manuscripts investigating the roles of Wnt signaling in MDR or studying the modulation of MDR through the inhibition of Wnt signaling have been involved in the study. The main focus of the manuscript is regulation of MDR related transporters by canonical Wnt signaling pathway.

Result and conclusion: Wnt signaling has been involved in several pathophysiological states, including carcinogenesis and embryonic development. Wnt signaling is linked to various aspects of MDR including P-glycoprotein and multidrug resistance protein 1 regulation through its canonical pathways. Aberrant activation of Wnt/β- catenin signaling leads to the induction of cancer MDR mainly through the overexpression and/or over-activation of MDR related transporters. Accordingly, Wnt/β-catenin signaling can be a potential target for modulating cancer MDR.

Keywords: Wnt-β-catenin; cancer; cancer stem cell; chemotherapeutic; embryogenesis; miRNA; multidrug resistance..

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
Cell Line, Tumor
Drug Resistance, Multiple*
Drug Resistance, Neoplasm*
Humans
Neoplasms / drug therapy
Neoplasms / metabolism*
Wnt Signaling Pathway*

Substances

ABCB1 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1