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NKD2, a negative regulator of Wnt signaling, suppresses tumor growth and metastasis in osteosarcoma
Open accessAbstract
Osteosarcoma (OS) is the most frequent pediatric malignant bone tumor that has a high propensity for metastases. Through osteoblast-specific alteration of p53 status, we developed a genetically engineered mouse model of localized and metastatic OS to gain an understanding into the molecular pathogenesis of OS. Microarray analysis of both localized tumors and metastatic tumors identified the downregulation of the naked cuticle homolog 2 (NKD2) gene, a negative regulator of Wnt signaling. Overexpression of NKD2 in metastatic human and mouse OS cells significantly decreases cell proliferation, migration and invasion ability in vitro and drastically diminishes OS tumor growth and metastasis in vivo, whereas downregulation enhances migratory and invasive potential. Evaluation of NKD2-overexpressing tumors revealed upregulation of tumor-suppressor genes and downregulation of molecules involved in blood vessel formation and cell migration. Furthermore, assessment of primary human OS revealed downregulation of NKD2 in metastatic and recurrent OS. Finally, we provide biological evidence that use of small-molecule inhibitors targeting the Wnt pathway can have therapeutic efficacy in decreasing metastatic properties in OS. Our studies provide compelling evidence that downregulation of NKD2 expression and alterations in associated regulated pathways have a significant role in driving OS tumor growth and metastasis.
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“Cultures derived from mice with spontaneous osteosarcoma 210 or from genetically engineered mouse models 100,213 are available to study disease biology or therapeutics in mice with intact immune systems.”
From Osteosarcoma (2022) · cites this paper as [213]
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Cites
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649
Self-citationThe Epidemiology of Osteosarcoma
Ottaviani, G., & Jaffe, N. (2009) · Cancer treatment and research · doi:10.1007/978-1-4419-0284-9_1 · Cited by 1,793
Petitjean, A., Mathe, E., Kato, S., Ishioka, C., Tavtigian, S. V., Hainaut, P., & Olivier, M. (2007) · Human Mutation · doi:10.1002/humu.20495 · Cited by 1,598
Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome
Olive, K. P., Tuveson, D. A., Ruhe, Z. C., Yin, B., Willis, N. A., Bronson, R. T., Crowley, D., & Jacks, T. (2004) · Cell · doi:10.1016/j.cell.2004.11.004 · Cited by 1,308
When mutants gain new powers: News from the mutant p53 field
Brosh, R., & Rotter, V. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2693 · Cited by 1,132
Kager, L., Zoubek, A., Pötschger, U., Kastner, U., Flege, S., Kempf-Bielack, B., Branscheid, D., Kotz, R., Salzer-Kuntschik, M., Winkelmann, W., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.08.132 · Cited by 934
Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes
Molenaar, J. J., Köster, J., Zwijnenburg, D. A., Sluis, P. V., Valentijn, L. J., van der Ploeg, I., Hamdi, M., van Nes, J., Westerman, B. A., van Arkel, J., et al. (2012) · Nature · doi:10.1038/nature10910 · Cited by 873
Genetic determinants of cancer metastasis
Nguyen, D. X., & Massagué, J. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2101 · Cited by 814
Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma
Chen, X., Bahrami, A., Pappo, A., Easton, J., Dalton, J., Hedlund, E., Ellison, D., Shurtleff, S., Wu, G., Wei, L., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.003 · Cited by 752
Osteogenic sarcoma with clinically detectable metastasis at initial presentation.
Meyers, P. A., Heller, G., Healey, J. H., Huvos, A. G., Applewhite, A., Sun, M., & LaQuaglia, M. P. (1993) · Journal of Clinical Oncology · doi:10.1200/jco.1993.11.3.449 · Cited by 389
miRNA control of tumor cell invasion and metastasis
Baranwal, S., & Alahari, S. K. (2009) · International Journal of Cancer · doi:10.1002/ijc.25014 · Cited by 316
Molecular Pathogenesis of Osteosarcoma
Kansara, M., & Thomas, D. M. (2007) · DNA and Cell Biology · doi:10.1089/dna.2006.0505 · Cited by 280
Hoang, B. H., Kubo, T., Healey, J. H., Yang, R., Nathan, S. S., Kolb, E. A., Mazza, B., Meyers, P. A., & Gorlick, R. G. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-1952 · Cited by 261
Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis
Cheng, J. H., She, H., Han, Y., Wang, J., Xiong, S., Asahina, K., & Tsukamoto, H. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00263.2007 · Cited by 261
Lauvrak, S. U., Munthe, E., Kresse, S. H., Stratford, E. W., Namløs, H. M., Meza‐Zepeda, L. A., & Myklebost, O. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.549 · Cited by 252
An Orthotopic Model of Human Osteosarcoma Growth and Spontaneous Pulmonary Metastasis
Luu, H. H., Kang, Q., Park, J. K., Si, W., Luo, Q., Jiang, W., Yin, H. X., MONTAG, A. G., Simon, M. A., Peabody, T. D., et al. (2005) · Clinical & Experimental Metastasis · doi:10.1007/s10585-005-0365-9 · Cited by 237
Endogenous interferon-γ is required for efficient skeletal muscle regeneration
Cheng, M., Nguyen, M.-H., Fantuzzi, G., & Koh, T. J. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00568.2007 · Cited by 214
High metastatic potential in mice inheriting a targeted p53 missense mutation
Liu, G., McDonnell, T. J., Luna, R. M. D. O., Kapoor, M., Mims, B. H., El‐Naggar, A. K., & Lozano, G. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.8.4174 · Cited by 201
20 years studying p53 functions in genetically engineered mice
Donehower, L. A., & Lozano, G. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2731 · Cited by 196
Self-citationExpression and activity of osteoblast-targeted Cre recombinase transgenes in murine skeletal tissues
Liu, F., Woitge, H. W., Braut, A., Kronenberg, M. S., Lichtler, A. C., Mina, M., & Kream, B. E. (2004) · The International Journal of Developmental Biology · doi:10.1387/ijdb.041816fl · Cited by 195
Bacci, G., Briccoli, A., Rocca, M., Ferrari, S., Donati, D. M., Longhi, A., Bertoni, F., Bacchini, P., Giacomini, S., Forni, C., et al. (2003) · Annals of Oncology · doi:10.1093/annonc/mdg286 · Cited by 187
Dickkopf-3/REIC functions as a suppressor gene of tumor growth
Hsieh, S., Hsieh, P.-S., Chiu, C., & Chen, W.-Y. (2004) · Oncogene · doi:10.1038/sj.onc.1208138 · Cited by 168
Cell autonomous regulation of multiple Dishevelled-dependent pathways by mammalian Nkd
Yan, D. M., Wallingford, J. B., Sun, T., Nelson, A. M., Sakanaka, C., Reinhard, C., Harland, R. M., Fantl, W. J., & Williams, L. T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.071041898 · Cited by 167
naked cuticle targets dishevelled to antagonize Wnt signal transductionPreprint
Rousset, R., Mack, J. A., Wharton, K. A., Axelrod, J. D., Cadigan, K. M., Fish, M., Nusse, R., & Scott, M. P. (2001) · Genes & Development · doi:10.1101/gad.869201 · Cited by 160
Correlation between CpG methylation profiles and hormone receptor status in breast cancers
Feng, W., Shen, L., Wen, S., Rosen, D. G., Jelı́nek, J., Hu, X., Huan, S., Huang, M. L., Liu, J., Şahin, A. A., et al. (2007) · Breast Cancer Research · doi:10.1186/bcr1762 · Cited by 154
Frequent promoter hypermethylation of Wnt pathway inhibitor genes in malignant astrocytic gliomas
Götze, S., Wolter, M., Reifenberger, G., Müller, O., & Sievers, S. (2009) · International Journal of Cancer · doi:10.1002/ijc.24981 · Cited by 147
Wnt signaling and the regulation of bone mass
Baron, R., & Rawadi, G. (2007) · Current Osteoporosis Reports · doi:10.1007/s11914-007-0006-0 · Cited by 127
Wang, L. L. (2005) · The Cancer Journal · doi:10.1097/00130404-200507000-00005 · Cited by 126
Guo, Y., Zi, X., Koontz, M. Z., Kim, A., Xie, J., Gorlick, R. G., Holcombe, R. F., & Hoang, B. H. (2007) · Journal of Orthopaedic Research® · doi:10.1002/jor.20356 · Cited by 116
Downregulation of several fibulin genes in prostate cancer
Wlazlinski, A., Engers, R., Hoffmann, M. J., Hader, C., Jung, V., Müller, M., & Schulz, W. A. (2007) · The Prostate · doi:10.1002/pros.20667 · Cited by 105
Veeck, J., Bektas, N., Hartmann, A., Kristiansen, G., Heindrichs, U., Knüchel, R., & Dahl, E. (2008) · Breast Cancer Research · doi:10.1186/bcr2151 · Cited by 96
Kanda, M., Nomoto, S., Okamura, Y., Hayashi, M., Hishida, M., Fujii, T., Nishikawa, Y., Sugimoto, H., Takeda, S., & Nakao, A. (2011) · Molecular Carcinogenesis · doi:10.1002/mc.20735 · Cited by 86
Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog
Johnson, A. J. (1998) · Carcinogenesis · doi:10.1093/carcin/19.1.213 · Cited by 80
REIC/Dkk-3 induces cell death in human malignant glioma
Mizobuchi, Y., Matsuzaki, K., Kuwayama, K., Kitazato, K. T., Mure, H., Kageji, T., & Nagahiro, S. (2008) · Neuro-Oncology · doi:10.1215/15228517-2008-016 · Cited by 74
Li, C., Franklin, J. L., Graves‐Deal, R., Jerome, W. G., Cao, Z., & Coffey, R. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401294101 · Cited by 73
Brennecke, P., Arlt, M., Campanile, C., Husmann, K., Gvozdenovic, A., Apuzzo, T., Thelen, M., Born, W., & Fuchs, B. (2014) · Clinical & Experimental Metastasis · doi:10.1007/s10585-013-9632-3 · Cited by 73
Edamura, K., Nasu, Y., Takaishi, M., Kobayashi, T., Abarzúa, F., Sakaguchi, M., Kashiwakura, Y., Ebara, S., Saika, T., Watanabe, M., et al. (2007) · Cancer Gene Therapy · doi:10.1038/sj.cgt.7701071 · Cited by 64
Hu, T., Li, C., Cao, Z., Raay, T. J. V., Smith, J. G., Willert, K., Solnica‐Krezel, L., & Coffey, R. J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.075945 · Cited by 60
Miretti, S., Roato, I., Taulli, R., Ponzetto, C., Cilli, M., Olivero, M., Renzo, M. F. D., Godio, L., Albini, A., Buracco, P., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001828 · Cited by 60
Kimura, R., Ishikawa, C., Rokkaku, T., Janknecht, R., & Mori, N. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.04.008 · Cited by 56
Husmann, K., Arlt, M., Muff, R., Langsam, B., Bertz, J., Born, W., & Fuchs, B. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.11.006 · Cited by 51
A systems biology approach reveals common metastatic pathways in osteosarcoma
Flores, R. J., Li, Y., Yu, A. K.-T., Shen, J. J., Rao, P. H., Lau, S. S., Vannucci, M., Lau, C. C., & Man, T. (2012) · BMC Systems Biology · doi:10.1186/1752-0509-6-50 · Cited by 51
Self-citationLi, C., Hao, M., Cao, Z., Ding, W., Graves‐Deal, R., Hu, J., Piston, D. W., & Coffey, R. J. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-02-0172 · Cited by 43
Muff, R., Kumar, R. M. R., Botter, S. M., Born, W., & Fuchs, B. (2012) · Sarcoma · doi:10.1155/2012/937506 · Cited by 41
Hong, S., Briggs, J., Newman, R. J., Hoffman, K. E., Mendoza, A., LeRoith, D., Helman, L. J., Yakar, S., & Khanna, C. (2008) · International Journal of Cancer · doi:10.1002/ijc.24169 · Cited by 18
Generation and Characterization of p53 Mutant Mice
Dumble, M. L., Donehower, L. A., & Lu, X. (2003) · Humana Press eBooks · doi:10.1385/1-59259-408-5:29 · Cited by 12
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Beird, H. C., Bielack, S. S., Flanagan, A. M., Gill, J., Heymann, D., Janeway, K. A., Livingston, J. A., Roberts, R. D., Strauss, S. J., & Gorlick, R. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00409-y · Cited by 660
Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy
Cersosimo, F., Lonardi, S., Bernardini, G., Telfer, B., Mandelli, G. E., Santucci, A., Vermi, W., & Giurisato, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155207 · Cited by 280
Molecular genetics of osteosarcoma
Rickel, K., Fang, F., & Tao, J. (2016) · Bone · doi:10.1016/j.bone.2016.10.017 · Cited by 255
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Metadata
- Authors
- Zhao, S., Kurenbekova, L., Gao, Y., Roos, A., Creighton, C. J., Rao, P., Hicks, J., Man, T.-K., Lau, C., Brown, A. M. C., Jones, S. N., Lazar, A. J., Ingram, D., Lev, D., Donehower, L. A., & Yustein, J. T.
- Affiliations
- Baylor College of Medicine (US)
- Weill Cornell Medicine (US)
- University of Massachusetts Chan Medical School (US)
- The University of Texas MD Anderson Cancer Center (US)
- The Ohio State University (US)
- Corresponding author
- Yustein, J T
- ORCID
- Venue
- Oncogene
- Published
- 2015-01-12
- Volume
- 34
- Issue
- 39
- Pages
- 5069-5079
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC4802362
- OpenAlex
- W2069275038
- Cited by
- 139
- References
- 48
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 7 · 2023: 6 · 2022: 13 · 2021: 15 · 2020: 14 · 2019: 11 · 2018: 10 · 2017: 17 · 2016: 18 · 2015: 8
- FWCI
- 13.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA123238, P30CA125123)
- National Institute of General Medical Sciences (T32GM008539)
- Topics
- Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- NKD2, osteosarcoma, Wnt signaling, metastasis, tumor growth, cell migration, cell invasion, p53, genetically engineered mouse models, tumor suppressor, angiogenesis, recurrent osteosarcoma, Wnt pathway inhibitors
- MeSH terms
- Animals, Bone Neoplasms, Calcium-Binding Proteins, Carrier Proteins, Neoplasm Invasiveness, Neoplasm Metastasis, Osteosarcoma, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice, Wnt Signaling Pathway
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