A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis

Nature Genetics

Volumn 47, Issue 6, 2015, Pages 615-624

  Moriarity, Branden S ^a,b,c   Otto, George M ^a,b,c   Rahrmann, Eric P ^a,b,c   Rathe, Susan K ^c   Wolf, Natalie K ^a,c   Weg, Madison T ^a,c   Manlove, Luke A ^a   Larue, Rebecca S ^a,c   Temiz, Nuri A ^c   Molyneux, Sam D ^d   Choi, Kwangmin ^e   Holly, Kevin J ^a   Sarver, Aaron L ^c   Scott, Milcah C ^a,c   Forster, Colleen L ^a   Modiano, Jaime F ^a,b,c   Khanna, Chand ^f   Hewitt, Stephen M ^f   Khokha, Rama ^d   Yang, Yi ^g   Gorlick, Richard ^h   Dyer, Michael A ⁱ   Largaespada, David A ^a,b,c   more..

^a UNIVERSITY OF MINNESOTA   (United States)

^b UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^c UNIVERSITY OF MINNESOTA   (United States)

^d PRINCESS MARGARET HOSPITAL   (Canada)

^e CINCINNATI CHILDREN S HOSPITAL RESEARCH FOUNDATION   (United States)

^f NATIONAL CANCER INSTITUTE   (United States)

^g PEKING UNIVERSITY   (China)

^h CHILDREN S HOSPITAL AT MONTEFIORE   (United States)

ⁱ ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 2A; MAMMALIAN TARGET OF RAPAMYCIN; MERLIN; MITOGEN ACTIVATED PROTEIN KINASE; MYC PROTEIN; NEUROFIBROMIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN; PROTEIN KINASE B; PROTEIN KINASE B BETA; PROTEIN P53; SEMA4D PROTEIN; SEMA6D PROTEIN; SHORT HAIRPIN RNA; TRANSCRIPTION ACTIVATOR LIKE EFFECTOR NUCLEASE; UNCLASSIFIED DRUG; VIRUS LARGE T ANTIGEN; PTEN PROTEIN, MOUSE; SEMA4D PROTEIN, MOUSE; SEMA6D PROTEIN, MOUSE; SEMAPHORIN; TRANSPOSON;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARCINOGENESIS; CELL LOSS; COMMON INSERTION SITE; COMPARATIVE STUDY; CONTROLLED STUDY; DISTANT METASTASIS; FUNCTIONAL GENOMICS; GENE EXPRESSION; GENE INSERTION; GENE SILENCING; GENETIC ASSOCIATION; GENETIC IDENTIFICATION; GENETIC SCREENING; GENOMIC INSTABILITY; HUMAN; HUMAN CELL; LYMPH NODE METASTASIS; MOUSE; MUTAGENESIS; NERVE FIBER; NONHUMAN; ONCOGENE; OSTEOSARCOMA; PRIMARY TUMOR; PRIORITY JOURNAL; PROTO ONCOGENE; SIGNAL TRANSDUCTION; SLEEPING BEAUTY TRANSPOSON; SOMATIC CELL; TRANSPOSON; TUMOR GROWTH; ANIMAL; BONE TUMOR; DOG; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION; GENETICS; METABOLISM; PATHOLOGY; SECONDARY; TRANSGENIC MOUSE; TUMOR CELL LINE;

MUS;

ANIMALS; BONE NEOPLASMS; CARCINOGENESIS; CELL LINE, TUMOR; DNA TRANSPOSABLE ELEMENTS; DOGS; GENETIC PREDISPOSITION TO DISEASE; GENOMIC INSTABILITY; HUMANS; MICE, TRANSGENIC; MUTAGENESIS, INSERTIONAL; OSTEOSARCOMA; PTEN PHOSPHOHYDROLASE; SEMAPHORINS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84930061429     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3293     Document Type: Article

References (85)

1. Kansara, M. & Thomas, D.M. Molecular pathogenesis of osteosarcoma. DNA Cell Biol. 26, 1-18 (2007).
2. Allison, D.C. et al. A meta-analysis of osteosarcoma outcomes in the modern medical era. Sarcoma 2012, 704872 (2012).
3. Jaffe, N., Puri, A. & Gelderblom, H. Osteosarcoma: evolution of treatment paradigms. Sarcoma 2013, 203531 (2013).
4. Tsuchiya, H. et al. Effect of timing of pulmonary metastases identifcation on prognosis of patients with osteosarcoma: the Japanese Musculoskeletal Oncology Group study. J. Clin. Oncol. 20, 3470-3477 (2002).
5. Kager, L. et al. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J. Clin. Oncol. 21, 2011-2018 (2003).
6. Meyers, P.A. et al. Osteogenic sarcoma with clinically detectable metastasis at initial presentation. J. Clin. Oncol. 11, 449-453 (1993).
7. Dobson, J.M. Breed-predispositions to cancer in pedigree dogs. ISRN Vet. Sci. 2013, 2013:941275 (2013).
8. Overholtzer, M. et al. The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability. Proc. Natl. Acad. Sci. USA 100, 11547-11552 (2003).
9. Kansara, M., Teng, M.W., Smyth, M.J. & Thomas, D.M. Translational biology of osteosarcoma. Nat. Rev. Cancer 14, 722-735 (2014).
10. Kuijjer, M.L. et al. Identifcation of osteosarcoma driver genes by integrative analysis of copy number and gene expression data. Genes Chromosom. Cancer 51, 696-706 (2012).
11. Sadikovic, B. et al. Identifcation of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profling. Hum. Mol. Genet. 18, 1962-1975 (2009).
12. Kresse, S.H. et al. Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma. PLoS ONE 7, e48262 (2012).
13. Copeland, N.G. & Jenkins, N.A. Harnessing transposons for cancer gene discovery. Nat. Rev. Cancer 10, 696-706 (2010).
14. Chen, X. et al. Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Rep. 7, 104-112 (2014).
15. Jones, K.B. Osteosarcomagenesis: modeling cancer initiation in the mouse. Sarcoma 2011, 694136 (2011).
16. Rodda, S.J. & McMahon, A.P. Distinct roles for Hedgehog and canonical Wnt signaling in specifcation, differentiation and maintenance of osteoblast progenitors. Development 133, 3231-3244 (2006).
17. Olive, K.P. et al. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 119, 847-860 (2004).
18. Zhang, G., Li, M., Zhu, X., Bai, Y. & Yang, C. Knockdown of Akt sensitizes osteosarcoma cells to apoptosis induced by cisplatin treatment. Int. J. Mol. Sci. 12, 2994-3005 (2011).
19. Clark, J.C., Dass, C.R. & Choong, P. F. A review of clinical and molecular prognostic factors in osteosarcoma. J. Cancer Res. Clin. Oncol. 134, 281-297 (2008).
20. Sabile, A.A. et al. Caprin-1, a novel Cyr61-interacting protein, promotes osteosarcoma tumor growth and lung metastasis in mice. Biochim. Biophys. Acta 1832, 1173-1182 (2013).
21. Guo, W. et al. Expression of bone morphogenetic proteins and receptors in sarcomas. Clin. Orthop. Relat. Res. (365), 175-183 (1999).
22. Nakajima, G. et al. CDH11 expression is associated with survival in patients with osteosarcoma. Cancer Genomics Proteomics 5, 37-42 (2008).
23. Chueh, F.S. et al. Bufalin-inhibited migration and invasion in human osteosarcoma U-2 OS cells is carried out by suppression of the matrix metalloproteinase-2, ERK, and JNK signaling pathways. Environ. Toxicol. 29, 21-29 (2014).
24. Chen, L. et al. miR-16 inhibits cell proliferation by targeting IGF1R and the Raf1-MEK1/2-ERK1/2 pathway in osteosarcoma. FEBS Lett. 587, 1366-1372 (2013).
25. Osborne, T.S. et al. Evaluation of eIF4E expression in an osteosarcoma-specifc tissue microarray. J. Pediatr. Hematol. Oncol. 33, 524-528 (2011).
26. Xu, H., Mei, Q., Xiong, C. & Zhao, J. Tumor-suppressing effects of miR-141 in human osteosarcoma. Cell Biochem. Biophys. 69, 319-325 (2014).
27. Zhao, R., Ni, D., Tian, Y., Ni, B. & Wang, A. Aberrant ADAM10 expression correlates with osteosarcoma progression. Eur. J. Med. Res. 19, 9 (2014).
28. Toledo, S.R.C. et al. Bone deposition, bone resorption, and osteosarcoma. J. Orthop. Res. 28, 1142-1148 (2010).
29. Liu, Y. et al. Rapamycin increases pCREB, Bcl-2, and VEGF-A through ERK under normoxia. Acta Biochim. Biophys. Sin. (Shanghai) 45, 259-267 (2013).
30. Zhang, P., Yang, Y., Zweidler-McKay, P.A. & Hughes, D.P. Critical role of Notch signaling in osteosarcoma invasion and metastasis. Clin. Cancer Res. 14, 2962-2969 (2008); retracted 15 September 2013.
31. Patiño-García, A., Zalacaín, M., Marrodán, L., San-Julián, M. & Sierrasesúmaga, L. Methotrexate in pediatric osteosarcoma: response and toxicity in relation to genetic polymorphisms and dihydrofolate reductase and reduced folate carrier 1 expression. J. Pediatr. 154, 688-693 (2009).
32. Kim, K.O. et al. Proteomic identifcation of 14-3-3ε as a linker protein between pERK1/2 inhibition and BIM upregulation in human osteosarcoma cells. J. Orthop. Res. 32, 848-854 (2014).
33. de Nigris, F. et al. YY1 overexpression is associated with poor prognosis and metastasis-free survival in patients suffering osteosarcoma. BMC Cancer 11, 472 (2011).
34. Lu, X.Y. et al. Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma. Mol. Cancer Res. 6, 937-946 (2008).
35. Yuan, D. et al. Overexpression of fbroblast activation protein and its clinical implications in patients with osteosarcoma. J. Surg. Oncol. 108, 157-162 (2013).
36. Sato, H. et al. Repression of p53-dependent sequence-specifc transactivation by MEF2c. Biochem. Biophys. Res. Commun. 214, 468-474 (1995).
37. Zhu, Y., Zhou, J., Ji, Y. & Yu, B. Elevated expression of AKT2 correlates with disease severity and poor prognosis in human osteosarcoma. Mol. Med. Rep. 10, 737-742 (2014).
38. Han, K. et al. microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R. Int. J. Oncol. 45, 1437-1449 (2014).
39. Wang, K. & Zhang, X. Inhibition of SENP5 suppresses cell growth and promotes apoptosis in osteosarcoma cells. Exp. Ther. Med. 7, 1691-1695 (2014).
40. Jones, K.B. et al. miRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res. 72, 1865-1877 (2012).
41. Gao, Y., Luo, L., Li, S. & Yang, C. miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression. Biochem. Biophys. Res. Commun. 444, 230-234 (2014).
42. Song, Q.C. et al. Downregulation of microRNA-26a is associated with metastatic potential and the poor prognosis of osteosarcoma patients. Oncol. Rep. 31, 1263-1270 (2014).
43. Tesser-Gamba, F. et al. MAPK7 and MAP2K4 as prognostic markers in osteosarcoma. Hum. Pathol. 43, 994-1002 (2012).
44. Srivastava, A. et al. High WT1 expression is associated with very poor survival of patients with osteogenic sarcoma metastasis. Clin. Cancer Res. 12, 4237-4243 (2006).
45. Scott, M.C. et al. Molecular subtypes of osteosarcoma identifed by reducing tumor heterogeneity through an interspecies comparative approach. Bone 49, 356-367 (2011).
46. Freeman, S.S. et al. Copy number gains in EGFR and copy number losses in PTEN are common events in osteosarcoma tumors. Cancer 113, 1453-1461 (2008).
47. Xiao, A. et al. Somatic induction of Pten loss in a preclinical astrocytoma model reveals major roles in disease progression and avenues for target discovery and validation. Cancer Res. 65, 5172 (2005).
48. Neale, G. et al. Molecular characterization of the pediatric preclinical testing panel. Clin. Cancer Res. 14, 4572-4583 (2008).
49. Swiercz, J.M., Worzfeld, T. & Offermanns, S. ErbB-2 and Met reciprocally regulate cellular signaling via plexin-B1. J. Biol. Chem. 283, 1893-1901 (2008).
50. Jiang, L. et al. CLDN3 inhibits cancer aggressiveness via Wnt-EMT signaling and is a potential prognostic biomarker for hepatocellular carcinoma. Oncotarget. 5, 7663-7676 (2014).
51. Wang, S. et al. Prostate-specifc deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4, 209-221 (2003).
52. Williams, K.C. & Coppolino, M.G. SNARE-dependent interaction of Src, EGFR and β1 integrin regulates invadopodia formation and tumor cell invasion. J. Cell Sci. 127, 1712-1725 (2014).
53. Zhao, B. et al. MicroRNA let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting ITGB3 and MAP4K3. Cancer Lett. 342, 43-51 (2014).
54. Kusama, T. et al. Inactivation of Rho GTPases by p190 RhoGAP reduces human pancreatic cancer cell invasion and metastasis. Cancer Sci. 97, 848-853 (2006).
55. Song, C. et al. Expression of p114RhoGEF predicts lymph node metastasis and poor survival of squamous-cell lung carcinoma patients. Tumour Biol. 34, 1925-1933 (2013).
56. Zhou, C.X. & Gao, Y. Frequent genetic alterations and reduced expression of the Axin1 gene in oral squamous cell carcinoma: involvement in tumor progression and metastasis. Oncol. Rep. 17, 73-79 (2007).
57. Li, X. et al. PHLPP is a negative regulator of RAF1, which reduces colorectal cancer cell motility and prevents tumor progression in mice. Gastroenterology 146, 1301-1312 (2014).
58. Li, D. & Huang, Y. Knockdown of ubiquitin associated protein 2-like inhibits the growth and migration of prostate cancer cells. Oncol. Rep. 32, 1578-1584 (2014).
59. Keng, V.W. et al. A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma. Nat. Biotechnol. 27, 264-274 (2009).
60. Wu, X. et al. Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature 482, 529-533 (2012).
61. Klein, C.A. Parallel progression of primary tumours and metastases. Nat. Rev. Cancer 9, 302-312 (2009).
62. Loh, A.H. et al. Dissecting the PI3K signaling axis in pediatric solid tumors: novel targets for clinical integration. Front. Oncol. 3, 93 (2013).
63. Yue, B., Ren, Q., Su, T., Wang, L. & Zhang, L. ERK5 silencing inhibits invasion of human osteosarcoma cell via modulating the Slug/MMP-9 pathway. J. Clin. Exp. Pathol. 4, 2640-2647 (2014).
64. Geryk-Hall, M. & Hughes, D.P.M. Critical signaling pathways in bone sarcoma: candidates for therapeutic interventions. Curr. Oncol. Rep. 11, 446-453 (2009).
65. Rahrmann, E.P. Forward genetic screen for malignant peripheral nerve sheath tumor formation identifes novel genes and genetic pathways driving tumorigenesis. Nat. Genet. 45, 756-766 (2013).
66. Starr, T.K. et al. A transposon-based genetic screen in mice identifes genes altered in colorectal cancer. Science 323, 1747-1750 (2009).
67. Dupuy, A.J. et al. A modifed Sleeping Beauty transposon system that can be used to model a wide variety of human cancers in mice. Cancer Res. 69, 8150 (2009).
68. Cinamon, U., Avinoach, I. & Harell, M. Neurofbromatosis type 1, hyperparathyroidism, and osteosarcoma: interplay? Eur. Arch. Otorhinolaryngol. 259, 540-542 (2002).
69. Ferrari, A., Bisogno, G. & Carli, M. Management of childhood malignant peripheral nerve sheath tumor. Paediatr. Drugs 9, 239-248 (2007).
70. Chowdhry, M. et al. Bone sarcomas arising in patients with neurofbromatosis type 1. J. Bone Joint Surg. Br. 91, 1223 (2009).
71. McClatchey, A.I. et al. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev. 12, 1121-1133 (1998).
72. Stemmer-Rachamimov, A.O. et al. The NF2 gene and merlin protein in human osteosarcomas. Neurogenetics 2, 73-74 (1998).
73. Rudolph, K.L. et al. Longevity, stress response, and cancer in aging telomerase-defcient mice. Cell 96, 701-712 (1999).
74. Law, J.W.S. & Lee, A.Y.W. The role of semaphorins and their receptors in gliomas. J. Signal Transduct. 2012, 902854 (2012).
75. Catalano, A., Lazzarini, R., Di Nuzzo, S., Orciari, S. & Procopio, A. The plexin-A1 receptor activates vascular endothelial growth factor-receptor 2 and nuclear factor-κB to mediate survival and anchorage-independent growth of malignant mesothelioma cells. Cancer Res. 69, 1485-1493 (2009).
76. Negishi-Koga, T. et al. Suppression of bone formation by osteoclastic expression of semaphorin 4D. Nat. Med. 17, 1473-1480 (2011).
77. Patanè, S. et al. MET overexpression turns human primary osteoblasts into osteosarcomas. Cancer Res. 66, 4750-4757 (2006).
78. Akatsuka, T. et al. ErbB2 expression is correlated with increased survival of patients with osteosarcoma. Cancer 94, 1397-1404 (2002).
79. Zhou, H., Binmadi, N.O., Yang, Y., Proia, P. & Basile, J.R. Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression. Angiogenesis 15, 391-407 (2012).
80. Nguyen, D.X., Bos, P.D. & Massagué, J. Metastasis: from dissemination to organ-specifc colonization. Nat. Rev. Cancer 9, 274-284 (2009).
81. Ognjanovic, S., Olivier, M., Bergemann, T.L. & Hainaut, P. Sarcomas in TP53 germline mutation carriers. Cancer 118, 1387-1396 (2012).
82. Sarver, A.L., Erdman, J., Starr, T., Largaespada, D.A. & Silverstein, K.A. TAPDANCE: an automated tool to identify and annotate transposon insertion CISs and associations between CISs from next generation sequence data. BMC Bioinformatics 13, 154 (2012).
83. Brett, B.T. et al. Novel molecular and computational methods improve the accuracy of insertion site analysis in Sleeping Beauty-induced tumors. PLoS ONE 6, e24668 (2011).
84. Moriarity, B. & Largaespada, D.A. A comprehensive guide to Sleeping Beauty-based somatic transposon mutagenesis in the mouse. Curr. Protoc. Mouse Biol. 347-368 (2011).
85. Collier, L.S., Carlson, C.M., Ravimohan, S., Dupuy, A.J. & Largaespada, D.A. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature 436, 272-276 (2005).