The Roles of Secreted Wnt Ligands in Cancer

Author:

Werner Johannes12ORCID,Boonekamp Kim E.1ORCID,Zhan Tianzuo345ORCID,Boutros Michael15ORCID

Affiliation:

1. Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), Medical Faculty Mannheim, Heidelberg University, 69120 Heidelberg, Germany

2. Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany

3. Department of Medicine II, Medical Faculty Mannheim, Mannheim University Hospital, Heidelberg University, D-68167 Mannheim, Germany

4. Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, D-68167 Mannheim, Germany

5. DKFZ-Hector Cancer Institute, University Medical Center Mannheim, D-68167 Mannheim, Germany

Abstract

Wnt ligands are secreted signaling proteins that display a wide range of biological effects. They play key roles in stimulating Wnt signaling pathways to facilitate processes such as tissue homeostasis and regeneration. Dysregulation of Wnt signaling is a hallmark of many cancers and genetic alterations in various Wnt signaling components, which result in ligand-independent or ligand-dependent hyperactivation of the pathway that have been identified. Recently, research is focusing on the impact of Wnt signaling on the interaction between tumor cells and their micro-environment. This Wnt-mediated crosstalk can act either in a tumor promoting or suppressing fashion. In this review, we comprehensively outline the function of Wnt ligands in different tumor entities and their impact on key phenotypes, including cancer stemness, drug resistance, metastasis, and immune evasion. Lastly, we elaborate approaches to target Wnt ligands in cancer therapy.

Funder

DFG

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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