ArticleMolecular and cellular biology2015
Disruption of Wnt/β-Catenin Signaling and Telomeric Shortening Are Inextricable Consequences of Tankyrase Inhibition in Human Cells.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
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- Ectodermal Wnt signaling, cell fate determination, and polarity of the skate gill arch skeleton.eLife · 2023Article
- Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review).International journal of oncology · 2023Review
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- Synthesis and Cytotoxic Activity of 1,2,4-Triazolo-LinkedMolecules (Basel, Switzerland) · 2022Article
- The Role of Telomerase in Breast Cancer's Response to Therapy.International journal of molecular sciences · 2022Review
- What we have learnt fromHeliyon · 2022Review
- The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy.Biomarker research · 2021Review
- Wnt/β-catenin signaling in cancers and targeted therapies.Signal transduction and targeted therapy · 2021Review
- Bioactivity Studies of Hesperidin and XAV939.ACS omega · 2021Article
- Importance of WNT-dependent signaling for derivation and maintenance of primed pluripotent bovine embryonic stem cells†.Biology of reproduction · 2021Article
- Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunities.Journal of experimental & clinical cancer research : CR · 2021Review
- Genome-Wide Meta-Analysis Identifies Two Novel Risk Loci for Epilepsy.Frontiers in neuroscience · 2021Article
- Targeting the Wnt/β-Catenin Signaling Pathway as a Potential Therapeutic Strategy in Renal Tubulointerstitial Fibrosis.Frontiers in pharmacology · 2021Review
- Increased H3K4me3 methylation and decreased miR-7113-5p expression lead to enhanced Wnt/β-catenin signaling in immune cells from PTSD patients leading to inflammatory phenotype.Molecular medicine (Cambridge, Mass.) · 2020Article
- 3,4,5-Tri-Frontiers in cell and developmental biology · 2020Article
- Roles of the Wnt Signaling Pathway in Head and Neck Squamous Cell Carcinoma.Frontiers in molecular biosciences · 2020Review
- Poly(ADP-ribose) polymerase enzymes and the maintenance of genome integrity.Cellular and molecular life sciences : CMLS · 2020Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Maintenance of chromosomal ends (telomeres) directly contributes to cancer cell immortalization. The telomere protection enzymes belonging to the tankyrase (Tnks) subfamily of poly(ADP-ribose) polymerases (PARPs) have recently been shown to also control transcriptional response to secreted Wnt signaling molecules. Whereas Tnks inhibitors are currently being developed as therapeutic agents for targeting Wnt-related cancers and as modulators of Wnt signaling in tissue-engineering agendas, their impact on telomere length maintenance remains unclear. Here, we leveraged a collection of Wnt pathway inhibitors with previously unassigned mechanisms of action to identify novel pharmacophores supporting Tnks inhibition. A multifaceted experimental approach that included structural, biochemical, and cell biological analyses revealed two distinct chemotypes with selectivity for Tnks enzymes. Using these reagents, we revealed that Tnks inhibition rapidly induces DNA damage at telomeres and telomeric shortening upon long-term chemical exposure in cultured cells. On the other hand, inhibitors of the Wnt acyltransferase Porcupine (Porcn) elicited neither effect. Thus, Tnks inhibitors impact telomere length maintenance independently of their affects on Wnt/β-catenin signaling. We discuss the implications of these findings for anticancer and regenerative medicine agendas dependent upon chemical inhibitors of Wnt/β-catenin signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.