Wnt signalling pathways in chronic lymphocytic leukaemia and B‐cell lymphomas

Janovská, Pavlína; Bryja, Vı́tězslav

doi:10.1111/bph.13949

Cited by 51 publications

(39 citation statements)

References 132 publications

(214 reference statements)

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“…Because RYK controls pathways affecting cell polarity, motility, and differentiation, it is not surprising that deregulation of RYK signaling is also associated with cancers, including hematological malignancies. The RYK‐associated PCP pathway and Rho‐dependent signaling have been proven to be important for the pathogenesis of CLL . Mutations in the RYK gene, among others, have been found in CLL patient samples .…”

Section: Ryk Signaling In Hematopoietic Cellsmentioning

confidence: 99%

“…The RYK‐associated PCP pathway and Rho‐dependent signaling have been proven to be important for the pathogenesis of CLL . Mutations in the RYK gene, among others, have been found in CLL patient samples . Moreover, high expression levels of RYK have been found in leukemia‐derived cell lines as well as leukemia patient samples from bone marrow and peripheral blood …”

Section: Ryk Signaling In Hematopoietic Cellsmentioning

confidence: 99%

“…The RYK-associated PCP pathway and Rhodependent signaling have been proven to be important for the pathogenesis of CLL. 14 has been hindered due to poor immunogenicity of its extracellular region and a lack of structural information about its interaction with other receptors and Wnt ligands. 69 However, a fully human monoclonal antibody for RYK was recently developed by identifying anti-RYK WIF domain-specific scFvs (human single chain fragment variables) from a phage library.…”

Section: Ryk S I G Naling In Hematop Oie Ti C Cell Smentioning

confidence: 99%

“…1,[8][9][10] Interestingly, higher expression levels of these Wnt-binding receptor pseudokinases in different hematological cancers have prompted in depth studies of their oncogenic role in sustaining cancer cell survival and therapy resistance. [11][12][13][14] In recent years, significant progress has been made using preclinical and clinical models to demonstrate their potential in targeted therapies for cancer treatment, including hematological cancers, which are the focus of this review.…”

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confidence: 99%

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Targeting Wnt signaling pseudokinases in hematological cancers

Karvonen

Perttilä

Niininen

et al. 2018

European J of Haematology

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Recent studies showed that several pseudokinases from the receptor tyrosine kinase family are important players in regulating cancer cell invasion, metastasis, and drug resistance, suggesting that targeting these proteins can play a therapeutic role in cancer treatment. Receptor Tyr kinase-like orphan receptors (RORs), protein Tyr kinase 7 (PTK7) (also called colon carcinoma kinase 4 (CCK4)), and receptor-like Tyr kinase (RYK) are Wnt ligand binding receptors within the non-canonical Wnt signaling, with important roles in development, tissue homeostasis, and organogenesis. At the cellular level, these receptors transduce signals important for cell survival, migration, polarization, and chemotaxis. Considerable progress has been made in the last decade in the field of pseudokinase signaling, improving our understanding of their structure-function mechanisms, and intracellular network of transduction components. Consequently, their role in various diseases, including cancer, is now scrutinized for therapeutic interventions to improve treatment outcome. In this article, we review findings regarding molecular mechanisms and targeted therapies for ROR1, PTK7, and RYK in hematological malignancies.

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Section: Ryk Signaling In Hematopoietic Cellsmentioning

confidence: 99%

Section: Ryk Signaling In Hematopoietic Cellsmentioning

confidence: 99%

Section: Ryk S I G Naling In Hematop Oie Ti C Cell Smentioning

confidence: 99%

mentioning

confidence: 99%

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Targeting Wnt signaling pseudokinases in hematological cancers

Karvonen

Perttilä

Niininen

et al. 2018

European J of Haematology

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“…In this context, Alan Prem Kumar and co‐workers summarize what is known about WNT‐associated lncRNAs in female reproductive tract cancers (Ong et al ., ). While a lot of emphasis is on the importance of WNT/β‐catenin/dependent signalling and targeting it in oncology, Janovská and Bryja () demonstrate that in chronic lymphocytic leukaemia and related lymphomas, the β‐catenin‐independent planar cell polarity signalling has a crucial role. However, progress in understanding WNT signalling has not only been made in the field of oncology.…”

Section: Wnt2016@brno – the 2016 International Wnt Meeting At Masarykmentioning

confidence: 99%

WNT signalling: mechanisms and therapeutic opportunities

Schulte

Bryja

2017

British J Pharmacology

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At the same time as the mechanistic understanding of the WNT signalling system, with its family of 19 secreted lipoglycoproteins, 10 class Frizzled GPCRs (FZD 1-10 ), several single transmembrane-spanning receptors [LDL receptorrelated protein 5/6 (LRP5/6), ROR1/2, RYK and PTK7] and a plethora of extracellular modulators [Dickkopfs (DKKs), SFRPs, WIFs, etc.] at the core of the pathway, is improving it becomes obvious that targeting this system therapeutically comes both with great potential and substantial challenges. This themed section about WNT signalling in the British Journal of Pharmacology aims to underline the progress in our more and more detailed understanding of signalling mechanisms, to summarize emerging concepts for therapy and to highlight novel developments with therapeutic potential. In addition, we aim to bridge the scientific disciplines of cell biology, developmental biology, stem cell biology, oncology, drug development and pharmacology in order to promote a truly translational approach with the goal of obtaining more effective drugs, with higher selectivity and less unwanted side effects, for treating various human diseases. WNT2016@Brno -The 2016International WNT Meeting at Masaryk University, Brno, CZThe WNT meeting in Brno, the city of Gregor Johann Mendel, the founder of genetics, was a continuation of the EMBO conference series on WNT signalling and provided a broad overview of the exciting developments in the research field ranging from deeper structural and molecular insights to disease mechanisms and novel drug targets. In addition, this meeting marks the end of a successful international training network (WntsApp -www.wntsapp.eu) funded by the frame programme FP7 and the Marie Curie Actions/European Commission, in which several members of the conference's organizing committee and participants collaborated. Given the substantial and exciting progress in areas such as establishment and use of organoid cultures, receptor dynamics, WNT secretion, stem cell regulation, single-cell sequencing, novel treatment paradigms for human disease and drug development, an atmosphere of optimism and ambition was present at the meeting. The

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The WNT/β‐catenin dependent transcription: A tissue‐specific business

Söderholm

Cantù

2020

WIREs Mechanisms of Disease

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β‐catenin‐mediated Wnt signaling is an ancient cell‐communication pathway in which β‐catenin drives the expression of certain genes as a consequence of the trigger given by extracellular WNT molecules. The events occurring from signal to transcription are evolutionarily conserved, and their final output orchestrates countless processes during embryonic development and tissue homeostasis. Importantly, a dysfunctional Wnt/β‐catenin pathway causes developmental malformations, and its aberrant activation is the root of several types of cancer. A rich literature describes the multitude of nuclear players that cooperate with β‐catenin to generate a transcriptional program. However, a unified theory of how β‐catenin drives target gene expression is still missing. We will discuss two types of β‐catenin interactors: transcription factors that allow β‐catenin to localize at target regions on the DNA, and transcriptional co‐factors that ultimately activate gene expression. In contrast to the presumed universality of β‐catenin's action, the ensemble of available evidence suggests a view in which β‐catenin drives a complex system of responses in different cells and tissues. A malleable armamentarium of players might interact with β‐catenin in order to activate the right “canonical” targets in each tissue, developmental stage, or disease context. Discovering the mechanism by which each tissue‐specific β‐catenin response is executed will be crucial to comprehend how a seemingly universal pathway fosters a wide spectrum of processes during development and homeostasis. Perhaps more importantly, this could ultimately inform us about which are the tumor‐specific components that need to be targeted to dampen the activity of oncogenic β‐catenin. This article is categorized under: Cancer > Molecular and Cellular Physiology Cancer > Genetics/Genomics/Epigenetics Cancer > Stem Cells and Development

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Wnt signalling pathways in chronic lymphocytic leukaemia and B‐cell lymphomas

Abstract: This article is part of a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc.

Cited by 51 publications

References 132 publications

Targeting Wnt signaling pseudokinases in hematological cancers

Targeting Wnt signaling pseudokinases in hematological cancers

WNT signalling: mechanisms and therapeutic opportunities

The WNT/β‐catenin dependent transcription: A tissue‐specific business

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