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Wnt Signaling in Ewing Sarcoma, Osteosarcoma, and Malignant Peripheral Nerve Sheath Tumors

  • Cancer-induced Musculoskeletal Diseases (M Reagan and E Keller, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Wnt signaling plays a central role in development and homeostasis, and its dysregulation is a common event in many types of human cancer. Here we explore in detail the contributions of Wnt signaling to the initiation and maintenance of three types of saroma: Ewing sarcoma, osteosarcoma, and malignant peripheral nerve sheath tumors. This review provides an overview of the Wnt signaling pathway and explores in detail the current knowledge about its role in the initiation or maintenance of three tumor types: Ewing sarcoma, osteosarcoma, and malignant peripheral nerve sheath tumors.

Recent Findings

Recent work has assessed the role(s) of Wnt signaling within these cell types. This review provides an overview of the mechanistic insights that have been gained from a number of recent studies to set the foundation for potential therapeutic applications.

Summary

Wnt signaling has emerged as a potentially critical pathway in maintaining the growth of these types of tumors. Given the fact that many new inhibitors of the pathway have recently or will soon enter Phase 1 clinical trials, it is likely that assessment of their activity in these tumor types will occur in human patients.

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References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Joiner DM, Ke J, Zhong Z, Xu HE, Williams BO. LRP5 and LRP6 in development and disease. Trends Endocrinol Metab. 2013;24(1):31–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhong Z, Ethen NJ, Williams BO. WNT signaling in bone development and homeostasis. Wiley Interdiscip Rev Dev Biol. 2014;3(6):489–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Song X, Wang S, Li L. New insights into the regulation of Axin function in canonical Wnt signaling pathway. Protein Cell. 2014;5(3):186–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hrckulak D, Kolar M, Strnad H, Korinek V. TCF/LEF transcription factors: an update from the internet resources. Cancers (Basel). 2016;8(7).

    Article  PubMed Central  CAS  Google Scholar 

  5. Acebron SP, Niehrs C. beta-Catenin-independent roles of Wnt/LRP6 signaling. Trends Cell Biol. 2016;26(12):956–67.

    Article  CAS  PubMed  Google Scholar 

  6. Yang Y, Mlodzik M. Wnt-Frizzled/planar cell polarity signaling: cellular orientation by facing the wind (Wnt). Annu Rev Cell Dev Biol. 2015;31:623–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Veeman MT, Axelrod JD, Moon RT. A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell. 2003;5(3):367–77.

    Article  CAS  PubMed  Google Scholar 

  8. Green J, Nusse R, van Amerongen R. The role of Ryk and Ror receptor tyrosine kinases in Wnt signal transduction. Cold Spring Harb Perspect Biol. 2014;01:6(2).

    Google Scholar 

  9. Kuhl M. The WNT/calcium pathway: biochemical mediators, tools and future requirements. Front Biosci. 2004;9:967–74.

    Article  PubMed  Google Scholar 

  10. Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci. 2003;116(Pt 13):2627–34.

    Article  CAS  PubMed  Google Scholar 

  11. Mason JJ, Williams BO. SOST and DKK: antagonists of LRP family signaling as targets for treating bone disease. J Osteoporos. 2010;01:2010.

    Google Scholar 

  12. Zhang X, Cheong SM, Amado NG, Reis AH, MacDonald BT, Zebisch M, et al. Notum is required for neural and head induction via Wnt deacylation, oxidation, and inactivation. Dev Cell. 2015;32(6):719–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kakugawa S, Langton PF, Zebisch M, Howell SA, Chang TH, Liu Y, et al. Notum deacylates Wnt proteins to suppress signalling activity. Nature. 2015;519(7542):187–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang X, Abreu JG, Yokota C, MacDonald BT, Singh S, Coburn KL, et al. Tiki1 is required for head formation via Wnt cleavage-oxidation and inactivation. Cell. 2012;149(7):1565–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. de Lau W, Peng WC, Gros P, Clevers H. The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength. Genes Dev. 2014;28(4):305–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Streich Jr FC, Haas AL. Activation of ubiquitin and ubiquitin-like proteins. Subcell Biochem. 2010;54:1–16.

    Article  CAS  PubMed  Google Scholar 

  17. Cadigan KM. Receptor endocytosis: Frizzled joins the ubiquitin club. EMBO J. 2010;29(13):2099–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mukai A, Yamamoto-Hino M, Awano W, Watanabe W, Komada M, Goto S. Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt. EMBO J. 2010;29(13):2114–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Goh LK, Sorkin A. Endocytosis of receptor tyrosine kinases. Cold Spring Harb Perspect Biol. 2013;5(5):a017459.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Knight MN, Hankenson KD. R-spondins: novel matricellular regulators of the skeleton. Matrix Biol. 2014;37:157–61.

    Article  CAS  PubMed  Google Scholar 

  21. Polakis P. Wnt signaling in cancer. Cold Spring Harb Perspect Biol. 2012;01:4(5).

    Google Scholar 

  22. •• Hao HX, Jiang X, Cong F. Control of Wnt receptor turnover by R-spondin-ZNRF3/RNF43 signaling module and its dysregulation in cancer. Cancers (Basel). 2016;8(6). This review provides an outstanding overview of the recently elucidated genetic changes that increase Wnt receptor availability on the cell surface which may drive tumorigenesis.

    Article  PubMed Central  CAS  Google Scholar 

  23. Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36(11):1461–73.

    Article  CAS  PubMed  Google Scholar 

  24. Cironi L, Petricevic T, Fernandes Vieira V, Provero P, Fusco C, Cornaz S, et al. The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma. Sci Rep. 2016;6:22113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nielsen TO, Poulin NM, Ladanyi M. Synovial sarcoma: recent discoveries as a roadmap to new avenues for therapy. Cancer Discov. 2015;5(2):124–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Trautmann M, Sievers E, Aretz S, Kindler D, Michels S, Friedrichs N, et al. SS18-SSX fusion protein-induced Wnt/beta-catenin signaling is a therapeutic target in synovial sarcoma. Oncogene. 2014;33(42):5006–16.

    Article  CAS  PubMed  Google Scholar 

  27. Barham W, Frump AL, Sherrill TP, Garcia CB, Saito-Diaz K, VanSaun MN, et al. Targeting the Wnt pathway in synovial sarcoma models. Cancer Discov. 2013;3(11):1286–301.

    Article  CAS  PubMed  Google Scholar 

  28. Chen C, Zhao M, Tian A, Zhang X, Yao Z, Ma X. Aberrant activation of Wnt/beta-catenin signaling drives proliferation of bone sarcoma cells. Oncotarget. 2015;6(19):17570–83.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Vijayakumar S, Liu G, Rus IA, Yao S, Chen Y, Akiri G, et al. High-frequency canonical Wnt activation in multiple sarcoma subtypes drives proliferation through a TCF/beta-catenin target gene, CDC25A. Cancer Cell. 2011;19(5):601–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Uren A, Wolf V, Sun YF, Azari A, Rubin JS, Toretsky JA. Wnt/Frizzled signaling in Ewing sarcoma. Pediatr Blood Cancer. 2004;43(3):243–9.

    Article  PubMed  Google Scholar 

  31. Baird K, Davis S, Antonescu CR, Harper UL, Walker RL, Chen Y, et al. Gene expression profiling of human sarcomas: insights into sarcoma biology. Cancer Res. 2005;65(20):9226–35.

    Article  CAS  PubMed  Google Scholar 

  32. Gibault L, Perot G, Chibon F, Bonnin S, Lagarde P, Terrier P, et al. New insights in sarcoma oncogenesis: a comprehensive analysis of a large series of 160 soft tissue sarcomas with complex genomics. J Pathol. 2011;223(1):64–71.

    Article  CAS  PubMed  Google Scholar 

  33. Kelleher FC, O'Sullivan H. FOXM1 in sarcoma: role in cell cycle, pluripotency genes and stem cell pathways. Oncotarget. 2016;7(27):42792–804.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Dancsok AR, Asleh-Aburaya K, Nielsen TO. Advances in sarcoma diagnostics and treatment. Oncotarget. 2017;8(4):7068–93.

    Article  PubMed  Google Scholar 

  35. Esiashvili N, Goodman M, Marcus Jr RB. Changes in incidence and survival of Ewing sarcoma patients over the past 3 decades: surveillance epidemiology and end results data. J Pediatr Hematol Oncol. 2008;30(6):425–30.

    Article  PubMed  Google Scholar 

  36. Pizzo PA, Poplack DG. Principles and practice of pediatric oncology. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2006.

    Google Scholar 

  37. Tirode F, Laud-Duval K, Prieur A, Delorme B, Charbord P, Delattre O. Mesenchymal stem cell features of Ewing tumors. Cancer Cell. 2007;11(5):421–9.

    Article  CAS  PubMed  Google Scholar 

  38. von Levetzow C, Jiang X, Gwye Y, von Levetzow G, Hung L, Cooper A, et al. Modeling initiation of Ewing sarcoma in human neural crest cells. PLoS One. 2011;6(4), e19305.

    Article  CAS  Google Scholar 

  39. Staege MS, Hutter C, Neumann I, Foja S, Hattenhorst UE, Hansen G, et al. DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets. Cancer Res. 2004;64(22):8213–21.

    Article  CAS  PubMed  Google Scholar 

  40. Minas TZ, Surdez D, Javaheri T, Tanaka M, Howarth M, Kang HJ, et al. Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model. Oncotarget. 2016.

  41. Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992;359(6391):162–5.

    Article  CAS  PubMed  Google Scholar 

  42. Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, et al. The Ewing family of tumors--a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med. 1994;331(5):294–9.

    Article  CAS  PubMed  Google Scholar 

  43. Kauer M, Ban J, Kofler R, Walker B, Davis S, Meltzer P, et al. A molecular function map of Ewing's sarcoma. PLoS One. 2009;4(4), e5415.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Brohl AS, Solomon DA, Chang W, Wang J, Song Y, Sindiri S, et al. The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation. PLoS Genet. 2014;10(7), e1004475.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Crompton BD, Stewart C, Taylor-Weiner A, Alexe G, Kurek KC, Calicchio ML, et al. The genomic landscape of pediatric ewing sarcoma. Cancer Discov. 2014;4(11):1326–41.

    Article  CAS  PubMed  Google Scholar 

  46. Tirode F, Surdez D, Ma X, Parker M, Le Deley MC, Bahrami A, et al. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov. 2014;4(11):1342–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Vijayaragavan K, Szabo E, Bosse M, Ramos-Mejia V, Moon RT, Bhatia M. Noncanonical Wnt signaling orchestrates early developmental events toward hematopoietic cell fate from human embryonic stem cells. Cell Stem Cell. 2009;4(3):248–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tanaka M, Yamazaki Y, Kanno Y, Igarashi K, Aisaki K, Kanno J, et al. Ewing's sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors. J Clin Invest. 2014;124(7):3061–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Javaheri T, Kazemi Z, Pencik J, Pham HT, Kauer M, Noorizadeh R, et al. Increased survival and cell cycle progression pathways are required for EWS/FLI1-induced malignant transformation. Cell Death Dis. 2016;7(10), e2419.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Leacock SW, Basse AN, Chandler GL, Kirk AM, Rakheja D, Amatruda JF. A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis. Dis Model Mech. 2012;5(1):95–106.

    Article  CAS  PubMed  Google Scholar 

  51. Navarro D, Agra N, Pestana A, Alonso J, Gonzalez-Sancho JM. The EWS/FLI1 oncogenic protein inhibits expression of the Wnt inhibitor DICKKOPF-1 gene and antagonizes beta-catenin/TCF-mediated transcription. Carcinogenesis. 2010;31(3):394–401.

    Article  CAS  PubMed  Google Scholar 

  52. •• Pedersen EA, Menon R, Bailey KM, Thomas DG, Van Noord RA, Tran J, et al. Activation of Wnt/beta-Catenin in Ewing sarcoma cells antagonizes EWS/ETS function and promotes phenotypic transition to more metastatic cell states. Cancer Res. 2016;76(17):5040–53. This manuscript presents novel concepts in terms of the relationship between heterogenous activation of Wnt signaling within subpopulations of tumors and disease progression.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Scannell CA, Pedersen EA, Mosher JT, Krook MA, Nicholls LA, Wilky BA, et al. LGR5 is expressed by Ewing sarcoma and potentiates Wnt/beta-Catenin signaling. Front Oncol. 2013;3:81.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Endo Y, Beauchamp E, Woods D, Taylor WG, Toretsky JA, Uren A, et al. Wnt-3a and Dickkopf-1 stimulate neurite outgrowth in Ewing tumor cells via a Frizzled3- and c-Jun N-terminal kinase-dependent mechanism. Mol Cell Biol. 2008;28(7):2368–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Jin Z, Zhao C, Han X, Han Y. Wnt5a promotes ewing sarcoma cell migration through upregulating CXCR4 expression. BMC Cancer. 2012;12:480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Techavichit P, Gao Y, Kurenbekova L, Shuck R, Donehower LA, Yustein JT. Secreted Frizzled-Related Protein 2 (sFRP2) promotes osteosarcoma invasion and metastatic potential. BMC Cancer. 2016;16(1):869.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. von Heyking K, Roth L, Ertl M, Schmidt O, Calzada-Wack J, Neff F, et al. The posterior HOXD locus: Its contribution to phenotype and malignancy of Ewing sarcoma. Oncotarget. 2016;7(27):41767–41780.

  58. Baker EK, Taylor S, Gupte A, Chalk AM, Bhattacharya S, Green AC, et al. Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma. Bone. 2015;73:223–32.

    Article  CAS  PubMed  Google Scholar 

  59. Kansara M, Tsang M, Kodjabachian L, Sims NA, Trivett MK, Ehrich M, et al. Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice. J Clin Invest. 2009;119(4):837–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hoang BH, Kubo T, Healey JH, Yang R, Nathan SS, Kolb EA, et al. Dickkopf 3 inhibits invasion and motility of Saos-2 osteosarcoma cells by modulating the Wnt-beta-catenin pathway. Cancer Res. 2004;64(8):2734–9.

    Article  CAS  PubMed  Google Scholar 

  61. Lin CH, Guo Y, Ghaffar S, McQueen P, Pourmorady J, Christ A, et al. Dkk-3, a secreted wnt antagonist, suppresses tumorigenic potential and pulmonary metastasis in osteosarcoma. Sarcoma. 2013;2013:147541.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Zhao S, Kurenbekova L, Gao Y, Roos A, Creighton CJ, Rao P, et al. NKD2, a negative regulator of Wnt signaling, suppresses tumor growth and metastasis in osteosarcoma. Oncogene. 2015;34(39):5069–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Li Z, Li Y, Wang N, Yang L, Zhao W, Zeng X. miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis in osteosarcoma cells. Biochem Biophys Res Commun. 2016;471(4):479–85.

    Article  CAS  PubMed  Google Scholar 

  64. Martins-Neves SR, Paiva-Oliveira DI, Wijers-Koster PM, Abrunhosa AJ, Fontes-Ribeiro C, Bovee JV, et al. Chemotherapy induces stemness in osteosarcoma cells through activation of Wnt/beta-catenin signaling. Cancer Lett. 2016;370(2):286–95.

    Article  CAS  PubMed  Google Scholar 

  65. Scholten 2nd DJ, Timmer CM, Peacock JD, Pelle DW, Williams BO, Steensma MR. Down regulation of Wnt signaling mitigates hypoxia-induced chemoresistance in human osteosarcoma cells. PLoS One. 2014;9(10), e111431.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Ma Y, Ren Y, Han EQ, Li H, Chen D, Jacobs JJ, et al. Inhibition of the Wnt-beta-catenin and Notch signaling pathways sensitizes osteosarcoma cells to chemotherapy. Biochem Biophys Res Commun. 2013;431(2):274–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ebert MS, Sharp PA. Roles for microRNAs in conferring robustness to biological processes. Cell. 2012;149(3):515–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wang Q, Cai J, Cai XH, Chen L. miR-346 regulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting the Wnt/beta-catenin pathway. PLoS One. 2013;8(9):e72266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Vanas V, Haigl B, Stockhammer V, Sutterluty-Fall H. MicroRNA-21 increases proliferation and cisplatin sensitivity of osteosarcoma-derived cells. PLoS One. 2016;11(8), e0161023.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Zhu Z, Tang J, Wang J, Duan G, Zhou L, Zhou X. MiR-138 acts as a tumor suppressor by targeting EZH2 and enhances cisplatin-induced apoptosis in osteosarcoma cells. PLoS One. 2016;11(3), e0150026.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Geng S, Gu L, Ju F, Zhang H, Wang Y, Tang H, et al. MicroRNA-224 promotes the sensitivity of osteosarcoma cells to cisplatin by targeting Rac1. J Cell Mol Med. 2016;20(9):1611–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wei R, Cao G, Deng Z, Su J, Cai L. miR-140-5p attenuates chemotherapeutic drug-induced cell death by regulating autophagy through inositol 1,4,5-trisphosphate kinase 2 (IP3k2) in human osteosarcoma cells. Biosci Rep. 2016;36(5).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Lammert M, Friedman JM, Kluwe L, Mautner VF. Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. Arch Dermatol. 2005;141(1):71–4.

    Article  PubMed  Google Scholar 

  74. Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM, et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A. 2010;152A(2):327–32.

    Article  CAS  PubMed  Google Scholar 

  75. Widemann BC. Current status of sporadic and neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors. Curr Oncol Rep. 2009;11(4):322–8.

    Article  PubMed  PubMed Central  Google Scholar 

  76. McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Montalto G, Cervello M, et al. Mutations and deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response. Oncotarget. 2012;3(9):954–87.

    Article  PubMed  PubMed Central  Google Scholar 

  77. •• Rahrmann EP, Watson AL, Keng VW, Choi K, Moriarity BS, Beckmann DA, et al. Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis. Nat Genet. 2013;45(7):756–66. This study helped establish Wnt/B-catenin signaling as a potential tumorigenic driver in NF1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Thomas LE, Winston J, Rad E, Mort M, Dodd KM, Tee AR, et al. Evaluation of copy number variation and gene expression in neurofibromatosis type-1-associated malignant peripheral nerve sheath tumours. Hum Genomics. 2015;9:3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Watson AL, Rahrmann EP, Moriarity BS, Choi K, Conboy CB, Greeley AD, et al. Canonical Wnt/beta-catenin signaling drives human schwann cell transformation, progression, and tumor maintenance. Cancer Discov. 2013;3(6):674–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Luscan A, Shackleford G, Masliah-Planchon J, Laurendeau I, Ortonne N, Varin J, et al. The activation of the WNT signaling pathway is a Hallmark in neurofibromatosis type 1 tumorigenesis. Clin Cancer Res. 2014;20(2):358–71.

    Article  CAS  PubMed  Google Scholar 

  81. Rey JP, Ellies DL. Wnt modulators in the biotech pipeline. Dev Dyn. 2010;239(1):102–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Serafino A, Sferrazza G, Colini Baldeschi A, Nicotera G, Andreola F, Pittaluga E, et al. Developing drugs that target the Wnt pathway: recent approaches in cancer and neurodegenerative diseases. Expert Opin Drug Discovery. 2017;12(2):169–86.

    Article  CAS  Google Scholar 

  83. Serafino A, Moroni N, Zonfrillo M, Andreola F, Mercuri L, Nicotera G, et al. WNT-pathway components as predictive markers useful for diagnosis, prevention and therapy in inflammatory bowel disease and sporadic colorectal cancer. Oncotarget. 2014;5(4):978–92.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Lu B, Green BA, Farr JM, Lopes FC, Van Raay TJ. Wnt Drug Discovery: Weaving Through the Screens, Patents and Clinical Trials. Cancers (Basel). 2016;8(9).

    Article  PubMed Central  CAS  Google Scholar 

  85. Ahmed K, Shaw HV, Koval A, Katanaev VL. A second WNT for old drugs: drug repositioning against WNT-dependent cancers. Cancers (Basel). 2016;8(7).

    Article  PubMed Central  CAS  Google Scholar 

  86. Ke J, Xu HE, Williams BO. Lipid modification in Wnt structure and function. Curr Opin Lipidol. 2013;24(2):129–33.

    Article  CAS  PubMed  Google Scholar 

  87. Tauriello DV, Maurice MM. The various roles of ubiquitin in Wnt pathway regulation. Cell Cycle. 2010;9(18):3700–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Cadigan KM, Waterman ML. TCF/LEFs and Wnt signaling in the nucleus. Cold Spring Harb Perspect Biol. 2012;01:4(11).

    Google Scholar 

  89. Surana R, Sikka S, Cai W, Shin EM, Warrier SR, Tan HJ, et al. Secreted frizzled related proteins: implications in cancers. Biochim Biophys Acta. 2014;1845(1):53–65.

    CAS  PubMed  Google Scholar 

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Acknowledgements

Work in these areas is supported by NIH grants to BOW (AR053293) and PJG (CA188314). MRS is supported by the Francis S. Collins Scholars Program in Neurofibromatosis Clinical and Translational Research sponsored by Johns Hopkins University’s Neurofibromatosis Therapeutic Acceleration Program (NTAP). PJG has received additional support from Alex’s Lemonade Stand Reach Award and Lily’s Garden Foundation. We thank Nicole Ethen for assistance with preparation of the figure.

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Authors and Affiliations

  1. Grand Rapids Medical Education Partners, Grand Rapids, MI, USA

    Matthew G. Pridgeon

  2. Spectrum Health Cancer Center, Spectrum Health System, Grand Rapids, MI, USA

    Matthew G. Pridgeon, Patrick J. Grohar & Matthew R. Steensma

  3. Helen De Vos Children’s Hospital, Grand Rapids, MI, USA

    Matthew G. Pridgeon, Patrick J. Grohar & Matthew R. Steensma

  4. Department of Pediatrics, Michigan State University, Grand Rapids, MI, USA

    Patrick J. Grohar

  5. Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, MI, USA

    Patrick J. Grohar, Matthew R. Steensma & Bart O. Williams

  6. Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, MI, USA

    Matthew R. Steensma

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Correspondence to Bart O. Williams.

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Matthew Pridgeon, Patrick Grohar, and Matthew Steensma declare no conflict of interest.

Bart Williams reports speaker honoraria from Vertex Pharmaceuticals and personal fees as a member of the board of scientific advisor from Surrozen.

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This article does not contain any studies that include human or animal subjects performed by any of the authors.

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BOW has received honoraria from Amgen and Vertex Pharmaceuticals. BOW serves on the Board of Scientific Advisors for, and owns stock inSurrozen.

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This article is part of the Topical Collection on Cancer-induced Musculoskeletal Diseases

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Pridgeon, M.G., Grohar, P.J., Steensma, M.R. et al. Wnt Signaling in Ewing Sarcoma, Osteosarcoma, and Malignant Peripheral Nerve Sheath Tumors. Curr Osteoporos Rep 15, 239–246 (2017). https://doi.org/10.1007/s11914-017-0377-9

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