To β or Not to β: How Important Is β-Catenin Dependent and Independent WNT Signaling in CLL?

Karol D Urbanek; Stephan Stilgenbauer; Daniel Mertens

doi:10.3390/cancers15010194

To β or Not to β: How Important Is β-Catenin Dependent and Independent WNT Signaling in CLL?

Cancers (Basel). 2022 Dec 28;15(1):194. doi: 10.3390/cancers15010194.

Authors

Karol D Urbanek¹, Stephan Stilgenbauer², Daniel Mertens^{1

3}

Affiliations

¹ Mechanisms of Leukemogenesis (B061), German Cancer Research Center, DKFZ, 69120 Heidelberg, Germany.
² Comprehensive Cancer Center Ulm, Ulm University Medical Center, 89081 Ulm, Germany.
³ Department of Internal Medicine III, University Hospital Ulm, 89081 Ulm, Germany.

Abstract

WNT pathways play an important role in cancer development and progression, but WNT pathways can also inhibit growth in melanoma, prostate, and ovarian cancers. Chronic lymphocytic leukemia (CLL) is known for its overexpression of several WNT ligands and receptors. Canonical WNT signaling is β-catenin-dependent, whereas non-canonical WNT signaling is β-catenin-independent. Research on WNT in CLL focuses mainly on non-canonical signaling due to the high expression of the WNT-5a receptor ROR1. However, it was also shown that mutations in canonical WNT pathway genes can lead to WNT activation in CLL. The focus of this review is β-catenin-independent signaling and β-catenin-dependent signaling within CLL cells and the role of WNT in the leukemic microenvironment. The major role of WNT pathways in CLL pathogenesis also makes WNT a possible therapeutic target, directly or in combination with other drugs.

Keywords: ROR1; WNT; chronic lymphocytic leukemia.

Publication types

Review

Grants and funding

This research was funded by the German Research Foundation DFG SFB 1074 projects B1 and B2 and the German Cancer Aid “Deutsche Krebshilfe” project 70114291.