4tor › Citations

Disruption of Wnt/β-Catenin Signaling and Telomeric Shortening Are Inextricable Consequences of Tankyrase Inhibition in Human Cells.

Kulak O, Chen H, Holohan B, Wu X, He H, Borek D, Otwinowski Z, Yamaguchi K, Garofalo LA, Ma Z, Wright W, Chen C, Shay JW, Zhang X, Lum L
Mol Cell Biol 35 2425-35 (2015)
Related entries: 4oa7, 4tos

Cited: 43 times
EuropePMC logo PMID: 25939383

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.

Articles - 4tor mentioned but not cited (2)

  1. Disruption of Wnt/β-Catenin Signaling and Telomeric Shortening Are Inextricable Consequences of Tankyrase Inhibition in Human Cells. Kulak O, Chen H, Holohan B, Wu X, He H, Borek D, Otwinowski Z, Yamaguchi K, Garofalo LA, Ma Z, Wright W, Chen C, Shay JW, Zhang X, Lum L. Mol Cell Biol 35 2425-2435 (2015)
  2. Regulation of tankyrase activity by a catalytic domain dimer interface. Fan C, Yarravarapu N, Chen H, Kulak O, Dasari P, Herbert J, Yamaguchi K, Lum L, Zhang X. Biochem Biophys Res Commun 503 1780-1785 (2018)


Reviews citing this publication (22)

  1. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Nusse R, Clevers H. Cell 169 985-999 (2017)
  2. The Wnt signaling pathway in cancer. Duchartre Y, Kim YM, Kahn M. Crit Rev Oncol Hematol 99 141-149 (2016)
  3. Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (Review). Katoh M. Int J Oncol 51 1357-1369 (2017)
  4. Wnt/β-catenin signaling in cancers and targeted therapies. Yu F, Yu C, Li F, Zuo Y, Wang Y, Yao L, Wu C, Wang C, Ye L. Signal Transduct Target Ther 6 307 (2021)
  5. Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding. Mariotti L, Pollock K, Guettler S. Br J Pharmacol 174 4611-4636 (2017)
  6. Poly(ADP-ribose) polymerase enzymes and the maintenance of genome integrity. Eisemann T, Pascal JM. Cell Mol Life Sci 77 19-33 (2020)
  7. Telomere and Telomerase Therapeutics in Cancer. Xu Y, Goldkorn A. Genes (Basel) 7 E22 (2016)
  8. Wnt Signaling in the Regulation of Immune Cell and Cancer Therapeutics. Haseeb M, Pirzada RH, Ain QU, Choi S. Cells 8 E1380 (2019)
  9. Emerging Insights into Wnt/β-catenin Signaling in Head and Neck Cancer. Alamoud KA, Kukuruzinska MA. J Dent Res 97 665-673 (2018)
  10. Targeting the Wnt/β-Catenin Signaling Pathway as a Potential Therapeutic Strategy in Renal Tubulointerstitial Fibrosis. Li SS, Sun Q, Hua MR, Suo P, Chen JR, Yu XY, Zhao YY. Front Pharmacol 12 719880 (2021)
  11. Wingless Signaling: A Genetic Journey from Morphogenesis to Metastasis. Bejsovec A. Genetics 208 1311-1336 (2018)
  12. Immune Cell Regulatory Pathways Unexplored as Host-Directed Therapeutic Targets for Mycobacterium tuberculosis: An Opportunity to Apply Precision Medicine Innovations to Infectious Diseases. Mahon RN, Hafner R. Clin Infect Dis 61Suppl 3 S200-16 (2015)
  13. Wnt Signaling Pathways in Keratinocyte Carcinomas. Lang CMR, Chan CK, Veltri A, Lien WH. Cancers (Basel) 11 E1216 (2019)
  14. Roles of the Wnt Signaling Pathway in Head and Neck Squamous Cell Carcinoma. Xie J, Huang L, Lu YG, Zheng DL. Front Mol Biosci 7 590912 (2020)
  15. Adjunct Strategies for Tuberculosis Vaccines: Modulating Key Immune Cell Regulatory Mechanisms to Potentiate Vaccination. Jayashankar L, Hafner R. Front Immunol 7 577 (2016)
  16. Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunities. Zamudio-Martinez E, Herrera-Campos AB, Muñoz A, Rodríguez-Vargas JM, Oliver FJ. J Exp Clin Cancer Res 40 144 (2021)
  17. The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy. Wang Z, Zhao T, Zhang S, Wang J, Chen Y, Zhao H, Yang Y, Shi S, Chen Q, Liu K. Biomark Res 9 68 (2021)
  18. Chemical Disruption of Wnt-dependent Cell Fate Decision-making Mechanisms in Cancer and Regenerative Medicine. Lum L, Chen C. Curr Med Chem 22 4091-4103 (2015)
  19. Pharmacologic Manipulation of Wnt Signaling and Cancer Stem Cells. Duchartre Y, Kim YM, Kahn M. Methods Mol Biol 1613 463-478 (2017)
  20. Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review). Chen Y, Chen M, Deng K. Int J Oncol 62 24 (2023)
  21. What we have learnt from Drosophila model organism: the coordination between insulin signaling pathway and tumor cells. Weina T, Ying L, Yiwen W, Huan-Huan Q. Heliyon 8 e09957 (2022)
  22. The Role of Telomerase in Breast Cancer's Response to Therapy. Judasz E, Lisiak N, Kopczyński P, Taube M, Rubiś B. Int J Mol Sci 23 12844 (2022)

Articles citing this publication (19)

  1. Molecular genetics and targeted therapy of WNT-related human diseases (Review). Katoh M, Katoh M. Int J Mol Med 40 587-606 (2017)
  2. XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway. Li C, Zheng X, Han Y, Lv Y, Lan F, Zhao J. Oncol Lett 15 8973-8982 (2018)
  3. β-catenin-mediated hair growth induction effect of 3,4,5-tri-O-caffeoylquinic acid. Bejaoui M, Villareal MO, Isoda H. Aging (Albany NY) 11 4216-4237 (2019)
  4. LNGFR targets the Wnt/β-catenin pathway and promotes the osteogenic differentiation in rat ectomesenchymal stem cells. Li G, Liu J, Wang Y, Yang K, Zhao M, Xiao Y, Wen X, Liu L. Sci Rep 7 11021 (2017)
  5. 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. Bam M, Yang X, Busbee BP, Aiello AE, Uddin M, Ginsberg JP, Galea S, Nagarkatti PS, Nagarkatti M. Mol Med 26 110 (2020)
  6. Structural and functional analysis of parameters governing tankyrase-1 interaction with telomeric repeat-binding factor 1 and GDP-mannose 4,6-dehydratase. Eisemann T, Langelier MF, Pascal JM. J Biol Chem 294 14574-14590 (2019)
  7. Inhibitors of telomerase and poly(ADP-ribose) polymerases synergize to limit the lifespan of pancreatic cancer cells. Burchett KM, Etekpo A, Batra SK, Yan Y, Ouellette MM. Oncotarget 8 83754-83767 (2017)
  8. Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1. Ryan K, Bolaňos B, Smith M, Palde PB, Cuenca PD, VanArsdale TL, Niessen S, Zhang L, Behenna D, Ornelas MA, Tran KT, Kaiser S, Lum L, Stewart A, Gajiwala KS. J Biol Chem 296 100251 (2021)
  9. Reversal of hyperactive Wnt signaling-dependent adipocyte defects by peptide boronic acids. Zhang T, Hsu FN, Xie XJ, Li X, Liu M, Gao X, Pei X, Liao Y, Du W, Ji JY. Proc Natl Acad Sci U S A 114 E7469-E7478 (2017)
  10. 3,4,5-Tri-O-Caffeoylquinic Acid Promoted Hair Pigmentation Through β-Catenin and Its Target Genes. Bejaoui M, Villareal MO, Isoda H. Front Cell Dev Biol 8 175 (2020)
  11. Importance of WNT-dependent signaling for derivation and maintenance of primed pluripotent bovine embryonic stem cells†. Xiao Y, Amaral TF, Ross PJ, Soto DA, Diffenderfer KE, Pankonin AR, Jeensuk S, Tríbulo P, Hansen PJ. Biol Reprod 105 52-63 (2021)
  12. Vascular disease-causing mutation, smooth muscle α-actin R258C, dominantly suppresses functions of α-actin in human patient fibroblasts. Liu Z, Chang AN, Grinnell F, Trybus KM, Milewicz DM, Stull JT, Kamm KE. Proc Natl Acad Sci U S A 114 E5569-E5578 (2017)
  13. Genome-Wide Meta-Analysis Identifies Two Novel Risk Loci for Epilepsy. Song M, Liu J, Yang Y, Lv L, Li W, Luo XJ. Front Neurosci 15 722592 (2021)
  14. Bioactivity Studies of Hesperidin and XAV939. Fazary AE, Alfaifi MY, Elbehairi SEI, Amer ME, Nasr MSM, Abuamara TMM, Badr DA, Ju YH, Mohamed AF. ACS Omega 6 20042-20052 (2021)
  15. The Recognition of Unrelated Ligands by Identical Proteins. Pottel J, Levit A, Korczynska M, Fischer M, Shoichet BK. ACS Chem Biol 13 2522-2533 (2018)
  16. Efflux inhibition by IWR-1-endo confers sensitivity to doxorubicin effects in osteosarcoma cells. Gustafson CT, Mamo T, Maran A, Yaszemski MJ. Biochem Pharmacol 150 141-149 (2018)
  17. Synthesis and Cytotoxic Activity of 1,2,4-Triazolo-Linked Bis-Indolyl Conjugates as Dual Inhibitors of Tankyrase and PI3K. Yakkala PA, Panda SR, Shafi S, Naidu VGM, Yar MS, Ubanako PN, Adeyemi SA, Kumar P, Choonara YE, Radchenko EV, Palyulin VA, Kamal A. Molecules 27 7642 (2022)
  18. Ectodermal Wnt signaling, cell fate determination, and polarity of the skate gill arch skeleton. Rees JM, Sleight VA, Clark SJ, Nakamura T, Gillis JA. Elife 12 e79964 (2023)
  19. Exceptional reactivity of the bridgehead amine on bicyclo[1.1.1]pentane. Lu Y, Chen C. ARKIVOC 2023 202312003 (2023)


Quick links