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Cancer and Metastasis Reviews
Published in: Cancer and Metastasis Reviews 4/2017

01-12-2017

The ubiquitin-proteasome pathway in adult and pediatric brain tumors: biological insights and therapeutic opportunities

Authors: Wafik Zaky, Christa Manton, Claudia P. Miller, Soumen Khatua, Vidya Gopalakrishnan, Joya Chandra

Published in: Cancer and Metastasis Reviews | Issue 4/2017

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Abstract

Nearly 20 years ago, the concept of targeting the proteasome for cancer therapy began gaining momentum. This concept was driven by increased understanding of the biology/structure and function of the 26S proteasome, insight into the role of the proteasome in transformed cells, and the synthesis of pharmacological inhibitors with clinically favorable features. Subsequent in vitro, in vivo, and clinical testing culminated in the FDA approval of three proteasome inhibitors—bortezomib, carfilzomib, and ixazomib—for specific hematological malignancies. However, despite in vitro and in vivo studies pointing towards efficacy in solid tumors, clinical responses broadly have been evasive. For brain tumors, a malignancy in dire need of new approaches both in adult and pediatric patients, this has also been the case. Elucidation of proteasome-dependent processes in specific types of brain tumors, the evolution of newer proteasome targeting strategies, and the use of proteasome inhibitors in combination strategies will clarify how these agents can be leveraged more effectively to treat central nervous system malignancies. Since brain tumors represent a heterogeneous subset of solid tumors, and in particular, pediatric brain tumors possess distinct biology from adult brain tumors, tailoring of proteasome inhibitor-based strategies to specific subtypes of these tumors will be critical for advancing care for affected patients, and will be discussed in this review.
Literature
1.
Howlander N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (2014) (eds). in National Cancer Institute, Bethesda, MD.
2.
Hershko, A., & Ciechanover, A. (1998). The ubiquitin system. Annual Review of Biochemistry, 67, 425–479.PubMedCrossRef
3.
4.
Hough, R., Pratt, G., & Rechsteiner, M. (1987). Purification of two high molecular weight proteases from rabbit reticulocyte lysate. The Journal of Biological Chemistry, 262, 8303–8313.PubMed
5.
Waxman, L., Fagan, J. M., Tanaka, K., & Goldberg, A. L. (1985). A soluble ATP-dependent system for protein degradation from murine erythroleukemia cells. Evidence for a protease which requires ATP hydrolysis but not ubiquitin. The Journal of Biological Chemistry, 260, 11994–12000.PubMed
6.
Driscoll, J., & Goldberg, A. L. (1990). The proteasome (multicatalytic protease) is a component of the 1500-kDa proteolytic complex which degrades ubiquitin-conjugated proteins. The Journal of Biological Chemistry, 265, 4789–4792.PubMed
7.
Ciechanover, A., Heller, H., Katz-Etzion, R., & Hershko, A. (1981). Activation of the heat-stable polypeptide of the ATP-dependent proteolytic system. Proceedings of the National Academy of Sciences of the United States of America, 78, 761–765.PubMedPubMedCentralCrossRef
8.
Pickart, C. M., & Rose, I. A. (1985). Functional heterogeneity of ubiquitin carrier proteins. The Journal of Biological Chemistry, 260, 1573–1581.PubMed
9.
Hershko, A., Heller, H., Elias, S., & Ciechanover, A. (1983). Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. The Journal of Biological Chemistry, 258, 8206–8214.PubMed
10.
van Nocker, S., & Vierstra, R. D. (1993). Multiubiquitin chains linked through lysine 48 are abundant in vivo and are competent intermediates in the ubiquitin proteolytic pathway. The Journal of Biological Chemistry, 268, 24766–24773.PubMed
11.
12.
Eytan, E., Ganoth, D., Armon, T., & Hershko, A. (1989). ATP-dependent incorporation of 20S protease into the 26S complex that degrades proteins conjugated to ubiquitin. Proceedings of the National Academy of Sciences of the United States of America, 86, 7751–7755.PubMedPubMedCentralCrossRef
13.
Glickman, M. H., & Ciechanover, A. (2002). The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiological Reviews, 82, 373–428.PubMedCrossRef
14.
Glickman, M. H., et al. (1998). A subcomplex of the proteasome regulatory particle required for ubiquitin-conjugate degradation and related to the COP9-signalosome and eIF3. Cell, 94, 615–623.PubMedCrossRef
15.
Groll, M., et al. (1999). The catalytic sites of 20S proteasomes and their role in subunit maturation: a mutational and crystallographic study. Proceedings of the National Academy of Sciences of the United States of America, 96, 10976–10983.PubMedPubMedCentralCrossRef
16.
Orlowski, M., & Wilk, S. (2000). Catalytic activities of the 20 S proteasome, a multicatalytic proteinase complex. Archives of Biochemistry and Biophysics, 383, 1–16.PubMedCrossRef
17.
Kisselev, A. F., & Goldberg, A. L. (2001). Proteasome inhibitors: from research tools to drug candidates. Chemistry & Biology, 8, 739–758.CrossRef
18.
Rechsteiner, M., Realini, C., & Ustrell, V. (2000). The proteasome activator 11 S REG (PA28) and class I antigen presentation. Biochemical Journal, 345(Pt 1), 1–15.PubMedPubMedCentralCrossRef
19.
Whitby, F. G., et al. (2000). Structural basis for the activation of 20S proteasomes by 11S regulators. Nature-London, 408, 115–120.PubMedCrossRef
20.
Rechsteiner, M., & Hill, C. P. (2005). Mobilizing the proteolytic machine: cell biological roles of proteasome activators and inhibitors. Trends in Cell Biology, 15, 27–33.PubMedCrossRef
21.
Noda, C., Tanahashi, N., Shimbara, N., Hendil, K. B., & Tanaka, K. (2000). Tissue distribution of constitutive proteasomes, immunoproteasomes, and PA28 in rats. Biochemical and Biophysical Research Communications, 277, 348–354.PubMedCrossRef
22.
Chen, X., Barton, L. F., Chi, A., Clurman, B. E., & Roberts, J. M. (2007). Ubiquitin-independent degradation of cell-cycle inhibitors by the REGgamma proteasome. Molecular Cell, 26, 843–852.PubMedPubMedCentralCrossRef
23.
Groettrup, M., et al. (1995). The interferon-gamma-inducible 11 S regulator (PA28) and the LMP2/LMP7 subunits govern the peptide production by the 20 S proteasome in vitro. The Journal of Biological Chemistry, 270, 23808–23815.PubMedCrossRef
24.
Cascio, P., Hilton, C., Kisselev, A. F., Rock, K. L., & Goldberg, A. L. (2001). 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide. The EMBO Journal, 20, 2357–2366.PubMedPubMedCentralCrossRef
25.
Toes, R., et al. (2001). Discrete cleavage motifs of constitutive and immunoproteasomes revealed by quantitative analysis of cleavage products. The Journal of Experimental Medicine, 194, 1–12.PubMedPubMedCentralCrossRef
26.
Piccinini, M., et al. (2005). Characterization of the 20S proteasome in human glioblastomas. Anticancer Research, 25, 3203–3210.PubMed
27.
28.
29.
Sturm, D., et al. (2012). Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell, 22, 425–437.PubMedCrossRef
30.
31.
Korshunov, A., et al. (2015). Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers. Acta Neuropathologica, 129, 669–678.PubMedCrossRef
32.
Liang, M. L., et al. (2008). Tyrosine kinase expression in pediatric high grade astrocytoma. Journal of Neuro-Oncology, 87, 247–253.PubMedCrossRef
33.
Puputti, M., et al. (2006). Amplification of KIT, PDGFRA, VEGFR2, and EGFR in gliomas. Molecular Cancer Research, 4, 927–934.PubMedCrossRef
34.
Peschard, P., & Park, M. (2003). Escape from Cbl-mediated downregulation: a recurrent theme for oncogenic deregulation of receptor tyrosine kinases. Cancer Cell, 3, 519–523.PubMedCrossRef
35.
Kuchay, S., et al. (2013). FBXL2- and PTPL1-mediated degradation of p110-free p85beta regulatory subunit controls the PI(3)K signalling cascade. Nature Cell Biology, 15, 472–480.PubMedCrossRef
36.
37.
Andrae, J., Gallini, R., & Betsholtz, C. (2008). Role of platelet-derived growth factors in physiology and medicine. Genes & Development, 22, 1276–1312.CrossRef
38.
Assanah, M. C., et al. (2009). PDGF stimulates the massive expansion of glial progenitors in the neonatal forebrain. Glia, 57, 1835–1847.PubMedCrossRef
39.
Clarke, I. D., & Dirks, P. B. (2003). A human brain tumor-derived PDGFR-alpha deletion mutant is transforming. Oncogene, 22, 722–733.PubMedCrossRef
40.
Paugh, B. S., et al. (2010). Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. Journal of Clinical Oncology, 28, 3061–3068.PubMedPubMedCentralCrossRef
41.
Dai, C., et al. (2001). PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes & Development, 15, 1913–1925.CrossRef
42.
Maxwell, M., et al. (1990). Coexpression of platelet-derived growth factor (PDGF) and PDGF-receptor genes by primary human astrocytomas may contribute to their development and maintenance. The Journal of Clinical Investigation, 86, 131–140.PubMedPubMedCentralCrossRef
43.
N. Cancer Genome Atlas Research. (2008). Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature, 455, 1061–1068.CrossRef
44.
Thorarinsdottir, H. K., et al. (2008). Protein expression of platelet-derived growth factor receptor correlates with malignant histology and PTEN with survival in childhood gliomas. Clinical Cancer Research, 14, 3386–3394.PubMedPubMedCentralCrossRef
45.
Shamah, S. M., Stiles, C. D., & Guha, A. (1993). Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells. Molecular and Cellular Biology, 13, 7203–7212.PubMedPubMedCentralCrossRef
46.
47.
Bredel, M., Pollack, I. F., Hamilton, R. L., & James, C. D. (1999). Epidermal growth factor receptor expression and gene amplification in high-grade non-brainstem gliomas of childhood. Clinical Cancer Research, 5, 1786–1792.PubMed
48.
Frederick, L., Wang, X. Y., Eley, G., & James, C. D. (2000). Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Research, 60, 1383–1387.PubMed
49.
50.
Hartman, Z., Zhao, H., & Agazie, Y. M. (2013). HER2 stabilizes EGFR and itself by altering autophosphorylation patterns in a manner that overcomes regulatory mechanisms and promotes proliferative and transformation signaling. Oncogene, 32, 4169–4180.PubMedCrossRef
51.
Koochekpour, S., et al. (1997). Met and hepatocyte growth factor/scatter factor expression in human gliomas. Cancer Research, 57, 5391–5398.PubMed
52.
Mosesson, Y., et al. (2003). Endocytosis of receptor tyrosine kinases is driven by monoubiquitylation, not polyubiquitylation. The Journal of Biological Chemistry, 278, 21323–21326.PubMedCrossRef
53.
Marmor, M. D., & Yarden, Y. (2004). Role of protein ubiquitylation in regulating endocytosis of receptor tyrosine kinases. Oncogene, 23, 2057–2070.PubMedCrossRef
54.
55.
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011). mTOR: from growth signal integration to cancer, diabetes and ageing. Nature Reviews. Molecular Cell Biology, 12, 21–35.PubMedCrossRef
56.
Fang, D., & Liu, Y. C. (2001). Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells. Nature Immunology, 2, 870–875.PubMedCrossRef
57.
Fan, Q. W., & Weiss, W. A. (2012). Inhibition of PI3K-Akt-mTOR signaling in glioblastoma by mTORC1/2 inhibitors. Methods in Molecular Biology, 821, 349–359.PubMedPubMedCentralCrossRef
58.
59.
Olovnikov, I. A., Kravchenko, J. E., & Chumakov, P. M. (2009). Homeostatic functions of the p53 tumor suppressor: regulation of energy metabolism and antioxidant defense. Seminars in Cancer Biology, 19, 32–41.PubMedCrossRef
60.
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997). Mdm2 promotes the rapid degradation of p53. Nature, 387, 296–299.PubMedCrossRef
61.
Momand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992). The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 69, 1237–1245.PubMedCrossRef
62.
63.
Wang, X., & Jiang, X. (2012). Mdm2 and MdmX partner to regulate p53. FEBS Letters, 586, 1390–1396.PubMedCrossRef
64.
Love, I. M., & Grossman, S. R. (2012). It takes 15 to tango: making sense of the many ubiquitin ligases of p53. Genes & Cancer, 3, 249–263.CrossRef
65.
Pomeroy, S. L. (1994). The p53 tumor suppressor gene and pediatric brain tumors. Current Opinion in Pediatrics, 6, 632–635.PubMedCrossRef
66.
Zhukova, N., et al. (2013). Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. Journal of Clinical Oncology, 31, 2927–2935.PubMedPubMedCentralCrossRef
67.
Pollack, I. F., et al. (1997). The relationship between TP53 mutations and overexpression of p53 and prognosis in malignant gliomas of childhood. Cancer Research, 57, 304–309.PubMed
68.
Kunkele, A., et al. (2012). Pharmacological activation of the p53 pathway by nutlin-3 exerts anti-tumoral effects in medulloblastomas. Neuro-Oncology, 14, 859–869.PubMedPubMedCentralCrossRef
69.
Knoepfler, P. S., Cheng, P. F., & Eisenman, R. N. (2002). N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes & Development, 16, 2699–2712.CrossRef
70.
Korshunov, A., et al. (2012). Biological and clinical heterogeneity of MYCN-amplified medulloblastoma. Acta Neuropathologica, 123, 515–527.PubMedCrossRef
71.
72.
73.
74.
Choi, S. H., Wright, J. B., Gerber, S. A., & Cole, M. D. (2010). Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells. Genes & Development, 24, 1236–1241.CrossRef
75.
Popov, N., Schulein, C., Jaenicke, L. A., & Eilers, M. (2010). Ubiquitylation of the amino terminus of Myc by SCF(beta-TrCP) antagonizes SCF(Fbw7)-mediated turnover. Nature Cell Biology, 12, 973–981.PubMedCrossRef
76.
von der Lehr, N., et al. (2003). The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription. Molecular Cell, 11, 1189–1200.PubMedCrossRef
77.
Adhikary, S., et al. (2005). The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation. Cell, 123, 409–421.PubMedCrossRef
78.
Zhao, X., et al. (2008). The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein. Nature Cell Biology, 10, 643–653.PubMedPubMedCentralCrossRef
79.
Penas, C., Ramachandran, V., & Ayad, N. G. (2011). The APC/C ubiquitin ligase: from cell biology to tumorigenesis. Frontiers in Oncology, 1, 60.PubMed
80.
Hsu, J. Y., Reimann, J. D., Sorensen, C. S., Lukas, J., & Jackson, P. K. (2002). E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1). Nature Cell Biology, 4, 358–366.PubMedCrossRef
81.
Lehman, N. L., Verschuren, E. W., Hsu, J. Y., Cherry, A. M., & Jackson, P. K. (2006). Overexpression of the anaphase promoting complex/cyclosome inhibitor Emi1 leads to tetraploidy and genomic instability of p53-deficient cells. Cell Cycle, 5, 1569–1573.PubMedCrossRef
82.
Margottin-Goguet, F., et al. (2003). Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Developmental Cell, 4, 813–826.PubMedCrossRef
83.
Guardavaccaro, D., et al. (2003). Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo. Developmental Cell, 4, 799–812.PubMedCrossRef
84.
Carrano, A. C., Eytan, E., Hershko, A., & Pagano, M. (1999). SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nature Cell Biology, 1, 193–199.PubMedCrossRef
85.
Marti, A., Wirbelauer, C., Scheffner, M., & Krek, W. (1999). Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation. Nature Cell Biology, 1, 14–19.PubMedCrossRef
86.
87.
Visintin, R., Prinz, S., & Amon, A. (1997). CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science, 278, 460–463.PubMedCrossRef
88.
Puram, S. V., & Bonni, A. (2011). Novel functions for the anaphase-promoting complex in neurobiology. Seminars in Cell & Developmental Biology, 22, 586–594.CrossRef
89.
Lasorella, A., et al. (2006). Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth. Nature, 442, 471–474.PubMedCrossRef
90.
91.
Schiffer, D., Cavalla, P., Fiano, V., Ghimenti, C., & Piva, R. (2002). Inverse relationship between p27/Kip.1 and the F-box protein Skp2 in human astrocytic gliomas by immunohistochemistry and Western blot. Neuroscience Letters, 328, 125–128.PubMedCrossRef
92.
Veeriah, S., et al. (2010). Somatic mutations of the Parkinson’s disease-associated gene PARK2 in glioblastoma and other human malignancies. Nature Genetics, 42, 77–82.PubMedCrossRef
93.
Ben-Neriah, Y., & Karin, M. (2011). Inflammation meets cancer, with NF-kappaB as the matchmaker. Nature Immunology, 12, 715–723.PubMedCrossRef
94.
Gilmore, T. D. (2006). Introduction to NF-kappaB: players, pathways, perspectives. Oncogene, 25, 6680–6684.PubMedCrossRef
95.
Harhaj, E. W., & Dixit, V. M. (2011). Deubiquitinases in the regulation of NF-kappaB signaling. Cell Research, 21, 22–39.PubMedCrossRef
96.
97.
Busino, L., et al. (2012). Fbxw7alpha- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nature Cell Biology, 14, 375–385.PubMedPubMedCentralCrossRef
98.
Fukushima, H., et al. (2012). SCF(Fbw7) modulates the NFkB signaling pathway by targeting NFkB2 for ubiquitination and destruction. Cell Reports, 1, 434–443.PubMedPubMedCentralCrossRef
99.
Bredel, M., et al. (2011). NFKBIA deletion in glioblastomas. The New England Journal of Medicine, 364, 627–637.PubMedCrossRef
100.
Wang, H., et al. (2004). Analysis of the activation status of Akt, NFkappaB, and Stat3 in human diffuse gliomas. Laboratory Investigation, 84, 941–951.PubMedCrossRef
101.
Hussain, S. F., et al. (2006). The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses. Neuro-Oncology, 8, 261–279.PubMedPubMedCentralCrossRef
102.
103.
Kool, M., et al. (2012). Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas. Acta Neuropathologica, 123, 473–484.PubMedPubMedCentralCrossRef
104.
DeSouza, R. M., Jones, B. R., Lowis, S. P., & Kurian, K. M. (2014). Pediatric medulloblastoma - update on molecular classification driving targeted therapies. Frontiers in Oncology, 4, 176.PubMedPubMedCentralCrossRef
105.
Schuller, U., et al. (2008). Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell, 14, 123–134.PubMedPubMedCentralCrossRef
106.
107.
Kool, M., et al. (2014). Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell, 25, 393–405.PubMedPubMedCentralCrossRef
108.
109.
Zurawel, R. H., Chiappa, S. A., Allen, C., & Raffel, C. (1998). Sporadic medulloblastomas contain oncogenic beta-catenin mutations. Cancer Research, 58, 896–899.PubMed
110.
111.
Rausch, T., et al. (2012). Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell, 148, 59–71.PubMedPubMedCentralCrossRef
112.
113.
Vriend, J., Ghavami, S., & Marzban, H. (2015). The role of the ubiquitin proteasome system in cerebellar development and medulloblastoma. Molecular Brain, 8, 64.PubMedPubMedCentralCrossRef
114.
Alvarez-Rodriguez, R., Barzi, M., Berenguer, J., & Pons, S. (2007). Bone morphogenetic protein 2 opposes Shh-mediated proliferation in cerebellar granule cells through a TIEG-1-based regulation of Nmyc. The Journal of Biological Chemistry, 282, 37170–37180.PubMedCrossRef
115.
116.
Wodarz, A., & Nusse, R. (1998). Mechanisms of Wnt signaling in development. Annual Review of Cell and Developmental Biology, 14, 59–88.PubMedCrossRef
117.
Mikesch, J. H., Steffen, B., Berdel, W. E., Serve, H., & Muller-Tidow, C. (2007). The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia. Leukemia, 21, 1638–1647.PubMedCrossRef
118.
Couffinhal, T., Dufourcq, P., & Duplaa, C. (2006). Beta-catenin nuclear activation: common pathway between Wnt and growth factor signaling in vascular smooth muscle cell proliferation? Circulation Research, 99, 1287–1289.PubMedCrossRef
119.
Northcott, P. A., et al. (2011). Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct. Acta Neuropathologica, 122, 231–240.PubMedPubMedCentralCrossRef
120.
121.
Scotting, P. J., Walker, D. A., & Perilongo, G. (2005). Childhood solid tumours: a developmental disorder. Nature Reviews. Cancer, 5, 481–488.PubMedCrossRef
122.
Yue, S., Chen, Y., & Cheng, S. Y. (2009). Hedgehog signaling promotes the degradation of tumor suppressor Sufu through the ubiquitin-proteasome pathway. Oncogene, 28, 492–499.PubMedCrossRef
123.
Kim, J. J., et al. (2011). Suppressor of fused controls mid-hindbrain patterning and cerebellar morphogenesis via GLI3 repressor. The Journal of Neuroscience, 31, 1825–1836.PubMedCrossRef
124.
Gulino, A., Di Marcotullio, L., Canettieri, G., De Smaele, E., & Screpanti, I. (2012). Hedgehog/Gli control by ubiquitination/acetylation interplay. Vitamins and Hormones, 88, 211–227.PubMedCrossRef
125.
Lau, A. W., Fukushima, H., & Wei, W. (2012). The Fbw7 and betaTRCP E3 ubiquitin ligases and their roles in tumorigenesis. Front Biosci (Landmark Ed), 17, 2197–2212.CrossRef
126.
Forget, A., et al. (2014). Shh signaling protects Atoh1 from degradation mediated by the E3 ubiquitin ligase Huwe1 in neural precursors. Developmental Cell, 29, 649–661.PubMedCrossRef
127.
Chen, D., et al. (2005). ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor. Cell, 121, 1071–1083.PubMedCrossRef
128.
Zhao, H., Ayrault, O., Zindy, F., Kim, J. H., & Roussel, M. F. (2008). Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development. Genes & Development, 22, 722–727.CrossRef
129.
Cao, Y., et al. (2014). Selective small molecule compounds increase BMP-2 responsiveness by inhibiting Smurf1-mediated Smad1/5 degradation. Scientific Reports, 4, 4965.PubMedPubMedCentralCrossRef
130.
Babaei-Jadidi, R., et al. (2011). FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation. The Journal of Experimental Medicine, 208, 295–312.PubMedPubMedCentralCrossRef
131.
Davis, R. J., Welcker, M., & Clurman, B. E. (2014). Tumor suppression by the Fbw7 ubiquitin ligase: mechanisms and opportunities. Cancer Cell, 26, 455–464.PubMedPubMedCentralCrossRef
132.
133.
Hede, S. M., Savov, V., Weishaupt, H., Sangfelt, O., & Swartling, F. J. (2014). Oncoprotein stabilization in brain tumors. Oncogene, 33, 4709–4721.PubMedCrossRef
134.
Hartmann, W., et al. (2006). Phosphatidylinositol 3′-kinase/AKT signaling is activated in medulloblastoma cell proliferation and is associated with reduced expression of PTEN. Clinical Cancer Research, 12, 3019–3027.PubMedCrossRef
135.
Wlodarski, P., Grajkowska, W., Lojek, M., Rainko, K., & Jozwiak, J. (2006). Activation of Akt and Erk pathways in medulloblastoma. Folia Neuropathologica, 44, 214–220.PubMed
136.
Yang, F., et al. (2012). Bortezomib induces apoptosis and growth suppression in human medulloblastoma cells, associated with inhibition of AKT and NF-kB signaling, and synergizes with an ERK inhibitor. Cancer Biology & Therapy, 13, 349–357.CrossRef
137.
Van Waes, C. (2007). Nuclear factor-kappaB in development, prevention, and therapy of cancer. Clinical Cancer Research, 13, 1076–1082.PubMedCrossRef
138.
Prasad, S., Ravindran, J., & Aggarwal, B. B. (2010). NF-kappaB and cancer: how intimate is this relationship. Molecular and Cellular Biochemistry, 336, 25–37.PubMedCrossRef
139.
Northcott, P. A., Dubuc, A. M., Pfister, S., & Taylor, M. D. (2012). Molecular subgroups of medulloblastoma. Expert Review of Neurotherapeutics, 12, 871–884.PubMedPubMedCentralCrossRef
140.
Sunwoo, J. B., et al. (2001). Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. Clinical Cancer Research, 7, 1419–1428.PubMed
141.
Adams, J. (2004). The development of proteasome inhibitors as anticancer drugs. Cancer Cell, 5, 417–421.PubMedCrossRef
142.
Spiller, S. E., Logsdon, N. J., Deckard, L. A., & Sontheimer, H. (2011). Inhibition of nuclear factor kappa-B signaling reduces growth in medulloblastoma in vivo. BMC Cancer, 11, 136.PubMedPubMedCentralCrossRef
143.
144.
Juvekar, A., et al. (2011). Bortezomib induces nuclear translocation of IkappaBalpha resulting in gene-specific suppression of NF-kappaB—dependent transcription and induction of apoptosis in CTCL. Molecular Cancer Research, 9, 183–194.PubMedPubMedCentralCrossRef
145.
Jariel-Encontre, I., Bossis, G., & Piechaczyk, M. (2008). Ubiquitin-independent degradation of proteins by the proteasome. Biochimica et Biophysica Acta, 1786, 153–177.PubMed
146.
Pagano, M., et al. (1995). Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science, 269, 682–685.PubMedCrossRef
147.
Maddika, S., et al. (2007). Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resistance Updates, 10, 13–29.PubMedCrossRef
148.
Epstein, F. H., Mitch, W. E., & Goldberg, A. L. (1996). Mechanisms of muscle wasting—the role of the ubiquitin–proteasome pathway. The New England Journal of Medicine, 335, 1897–1905.CrossRef
149.
Groll, M., Berkers, C. R., Ploegh, H. L., & Ovaa, H. (2006). Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome. Structure, 14, 451–456.PubMedCrossRef
150.
Berkers, C. R., et al. (2005). Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. Nature Methods, 2, 357–362.PubMedCrossRef
151.
Hideshima, T., et al. (2001). The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Research, 61, 3071–3076.PubMed
152.
Jagannath, S., et al. (2004). A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. British Journal of Haematology, 127, 165–172.PubMedCrossRef
153.
Richardson, P. G., et al. (2007). Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood, 110, 3557–3560.PubMedCrossRef
154.
Kane, R. C., Bross, P. F., Farrell, A. T., & Pazdur, R. (2003). Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. The Oncologist, 8, 508–513.PubMedCrossRef
155.
Kane, R. C., Farrell, A. T., Sridhara, R., & Pazdur, R. (2006). United States Food and Drug Administration approval summary: bortezomib for the treatment of progressive multiple myeloma after one prior therapy. Clinical cancer research : an official journal of the American Association for Cancer Research, 12, 2955–2960.CrossRef
156.
Kane, R. C., et al. (2007). Bortezomib for the treatment of mantle cell lymphoma. Clinical cancer research : an official journal of the American Association for Cancer Research, 13, 5291–5294.CrossRef
157.
Potts, B. C., et al. (2011). Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Current Cancer Drug Targets, 11, 254–284.PubMedPubMedCentralCrossRef
158.
Millward, M., et al. (2011). Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination. Investigational New Drugs, 30, 2303–2317.PubMedCrossRef
159.
Williams, P. G., et al. (2005). New cytotoxic salinosporamides from the marine Actinomycete Salinispora tropica. The Journal of Organic Chemistry, 70, 6196–6203.PubMedCrossRef
160.
Corey, E. J., & Li, W. D. (1999). Total synthesis and biological activity of lactacystin, omuralide and analogs. Chemical & Pharmaceutical Bulletin, 47, 1–10.CrossRef
161.
Feling, R. H., et al. (2003). Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus Salinospora. Angewandte Chemie (International Ed. in English), 42, 355–357.CrossRef
162.
Groll, M., Huber, R., & Potts, B. C. M. (2006). Crystal structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in complex with the 20S proteasome reveal important consequences of beta-lactone ring opening and a mechanism for irreversible binding. Journal of the American Chemical Society, 128, 5136–5141.PubMedCrossRef
163.
Manam, R. R., et al. (2008). Leaving groups prolong the duration of 20S proteasome inhibition and enhance the potency of salinosporamides. Journal of Medicinal Chemistry, 51, 6711–6724.PubMedCrossRef
164.
Miller, C. P., et al. (2011). Specific and prolonged proteasome inhibition dictates apoptosis induction by marizomib and its analogs. Chemico-Biological Interactions, 194, 58–68.PubMedPubMedCentralCrossRef
165.
Chauhan, D., et al. (2005). A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from bortezomib. Cancer Cell, 8, 407–419.PubMedCrossRef
166.
Kuhn, D. J., et al. (2009). Targeted inhibition of the immunoproteasome is a potent strategy against models of multiple myeloma that overcomes resistance to conventional drugs and nonspecific proteasome inhibitors. Blood, 113, 4667–4676.PubMedPubMedCentralCrossRef
167.
Muchamuel, T., et al. (2009). A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nature Medicine, 15, 781–787.PubMedCrossRef
168.
Basler, M., Dajee, M., Moll, C., Groettrup, M., & Kirk, C. J. (2010). Prevention of experimental colitis by a selective inhibitor of the immunoproteasome. Journal of Immunology, 185, 634–641.CrossRef
169.
Ohshima-Hosoyama, S., Davare, M. A., Hosoyama, T., Nelon, L. D., & Keller, C. (2011). Bortezomib stabilizes NOXA and triggers ROS-associated apoptosis in medulloblastoma. Journal of Neuro-Oncology, 105, 475–483.PubMedCrossRef
170.
171.
Taniguchi, E., et al. (2009). Bortezomib reverses a post-translational mechanism of tumorigenesis for patched1 haploinsufficiency in medulloblastoma. Pediatric Blood & Cancer, 53, 136–144.CrossRef
172.
173.
Dimopoulos, M. A., et al. (2017). Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. The Lancet Oncology, 18, 1327–1337.PubMedCrossRef
174.
Abbott, N. J., Patabendige, A. A. K., Dolman, D. E. M., Yusof, S. R., & Begley, D. J. (2010). Structure and function of the blood-brain barrier. Neurobiology of Disease, 37, 13–25.PubMedCrossRef
175.
Zünkeler, B., et al. (1996). Quantification and pharmacokinetics of blood-brain barrier disruption in humans. Journal of Neurosurgery, 85, 1056–1065.PubMedCrossRef
176.
Balyasnikova, I. V., Ferguson, S. D., Han, Y., Liu, F., & Lesniak, M. S. (2011). Therapeutic effect of neural stem cells expressing TRAIL and bortezomib in mice with glioma xenografts. Cancer Letters, 310, 148–159.PubMedPubMedCentralCrossRef
177.
Asklund, T., et al. (2012). Synergistic killing of glioblastoma stem-like cells by bortezomib and HDAC inhibitors. Anticancer Research, 32, 2407–2413.PubMed
178.
Premkumar, D. R., Jane, E. P., Agostino, N. R., DiDomenico, J. D., & Pollack, I. F. (2013). Bortezomib-induced sensitization of malignant human glioma cells to vorinostat-induced apoptosis depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation, Mcl-1 cleavage, and DNA damage. Molecular Carcinogenesis, 52, 118–133.PubMedCrossRef
179.
Friday, B. B., et al. (2012). Phase II trial of vorinostat in combination with bortezomib in recurrent glioblastoma: a north central cancer treatment group study. Neuro-Oncology, 14, 215–221.PubMedCrossRef
180.
Labussiere, M., Pinel, S., Delfortrie, S., Plenat, F., & Chastagner, P. (2008). Proteasome inhibition by bortezomib does not translate into efficacy on two malignant glioma xenografts. Oncology Reports, 20, 1283–1287.PubMed
181.
182.
Singh, A. V., et al. (2010). Pharmacodynamic and efficacy studies of the novel proteasome inhibitor NPI-0052 (marizomib) in a human plasmacytoma xenograft murine model. British Journal of Haematology, 149, 550–559.PubMedPubMedCentralCrossRef
183.
Di, K., et al. (2016). Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier. Neuro-Oncology, 18, 840–848.PubMedCrossRef
184.
Manton, C. A., et al. (2016). Induction of cell death by the novel proteasome inhibitor marizomib in glioblastoma in vitro and in vivo. Scientific Reports, 6, 18953.PubMedPubMedCentralCrossRef
185.
Berkowitz, A., & Walker, S. (2012). Bortezomib-induced peripheral neuropathy in patients with multiple myeloma. Clinical Journal of Oncology Nursing, 16, 86–89.PubMedCrossRef
186.
Argyriou, A. A., Iconomou, G., & Kalofonos, H. P. (2008). Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood, 112, 1593–1599.PubMedCrossRef
187.
Wolf, S., Barton, D., Kottschade, L., Grothey, A., & Loprinzi, C. (2008). Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies. European journal of cancer (Oxford, England : 1990), 44, 1507–1515.CrossRef
188.
Delforge, M., et al. (2010). Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. The Lancet. Oncology, 11, 1086–1095.PubMedCrossRef
189.
Zou, W., et al. (2006). Vitamin C inactivates the proteasome inhibitor PS-341 in human cancer cells. Clinical cancer research : an official journal of the American Association for Cancer Research, 12, 273–280.CrossRef
190.
Richardson PG et al., paper presented at the American Society of Hematology Meeting Abstract, Nov 01 2011.
191.
Yoo, J. Y., et al. (2014). Bortezomib-induced unfolded protein response increases oncolytic HSV-1 replication resulting in synergistic antitumor effects. Clinical Cancer Research, 20, 3787–3798.PubMedPubMedCentralCrossRef
192.
Yoo, J. Y., et al. (2016). Bortezomib treatment sensitizes oncolytic HSV-1-treated tumors to NK cell immunotherapy. Clinical Cancer Research, 22, 5265–5276.PubMedPubMedCentralCrossRef
193.
Leestemaker, Y., et al. (2017). Proteasome activation by small molecules. Cell Chemical Biology, 24, 725–736 e727.PubMedCrossRef
194.
Phuphanich, S., et al. (2010). Phase 1 clinical trial of bortezomib in adults with recurrent malignant glioma. Journal of Neuro-Oncology, 100, 95–103.PubMedCrossRef
195.
Blaney, S. M., et al. (2004). Phase I study of the proteasome inhibitor bortezomib in pediatric patients with refractory solid tumors: a Children’s Oncology Group study (ADVL0015). Journal of Clinical Oncology, 22, 4804–4809.PubMedCrossRef
196.
Portnow, J., et al. (2012). A phase I study of bortezomib and temozolomide in patients with advanced solid tumors. Cancer Chemotherapy and Pharmacology, 69, 505–514.PubMedCrossRef
197.
Yin, D., et al. (2005). Proteasome inhibitor PS-341 causes cell growth arrest and apoptosis in human glioblastoma multiforme (GBM). Oncogene, 24, 344–354.PubMedCrossRef
198.
Riordan, B., Yu, L. J., Hatsis, P., Brockman, A., Daniels, S., Stagliano, N., Finklestein, S., Ren, J., Milton, M., & Miwa, G. (2006). Study of brain and whole blood PK/PD of bortezomib in rat models. Journal of Clinical Oncology, 24, 12036.
199.
Muscal, J. A., et al. (2013). A phase I trial of vorinostat and bortezomib in children with refractory or recurrent solid tumors: a Children’s Oncology Group phase I consortium study (ADVL0916). Pediatric Blood & Cancer, 60, 390–395.CrossRef
200.
McCracken, D. J., Celano, E. C., Voloschin, A. D., Read, W. L., & Olson, J. J. (2016). Phase I trial of dose-escalating metronomic temozolomide plus bevacizumab and bortezomib for patients with recurrent glioblastoma. Journal of Neuro-Oncology, 130, 193–201.PubMedCrossRef
201.
Bota, D. A., et al. (2013). Proteasome inhibition with bortezomib induces cell death in GBM stem-like cells and temozolomide-resistant glioma cell lines, but stimulates GBM stem-like cells’ VEGF production and angiogenesis. Journal of Neurosurgery, 119, 1415–1423.PubMedPubMedCentralCrossRef
Metadata
Title
The ubiquitin-proteasome pathway in adult and pediatric brain tumors: biological insights and therapeutic opportunities
Authors
Wafik Zaky
Christa Manton
Claudia P. Miller
Soumen Khatua
Vidya Gopalakrishnan
Joya Chandra
Publication date
01-12-2017
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 4/2017
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-017-9700-2

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