1.Thakkar, J. P. et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiology Biomarkers and Prevention (2014). doi:10.1158/1055–9965.EPI–14–0275
2.Ostrom, Q. T., Liao, P., Stetson, L. C. & Barnholtz-Sloan, J. S. Epidemiology of Glioblastoma and Trends in Glioblastoma Survivorship. in Glioblastoma (2016). doi:10.1016/b978–0–323–47660–7.00002–1
3.Zong, H., Verhaak, R. G. W. & Canoll, P. The cellular origin for malignant glioma and prospects for clinical advancements. Expert Rev. Mol. Diagnosis 12, 383–394 (2012).
4.Stupp, R. et al. Radiotherapy plus Concomitant\nand Adjuvant Temozolomide for Glioblastoma. N. Engl. J. Med. 987–96 (2005). doi:10.1056/NEJMoa043330
5.Wilson, T., Karajannis, M. & Harter, D. Glioblastoma multiforme: State of the art and future therapeutics. Surg. Neurol. Int. (2014). doi:10.4103/2152–7806.132138
6.COHEN, S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J. Biol. Chem. (1962).
7.Sorkin, A. & Goh, L. K. Endocytosis and intracellular trafficking of ErbBs. Exp. Cell Res. 315, 683–696 (2009).
8.Tomas, A., Futter, C. E. & Eden, E. R. EGF receptor trafficking: Consequences for signaling and cancer. Trends in Cell Biology (2014). doi:10.1016/j.tcb.2013.11.002
9.Riese, D. J. & Stern, D. F. Specificity within the EGF family/ErbB receptor family signaling network. BioEssays (1998). doi:10.1002/(SICI)1521–1878(199801)20:1<41::AID-BIES7>3.0.CO;2-V
10.Felder, S. et al. Kinase activity controls the sorting of the epidermal growth factor receptor within the multivesicular body. Cell 61, 623–634 (1990).
11.Chakravarti, A. et al. The prognostic significance of phosphatidylinositol 3-kinase pathway activation in human gliomas. J. Clin. Oncol. 22, 1926–1933 (2004).
12.Arteaga, C. L. & Engelman, J. A. ERBB receptors: From oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell (2014). doi:10.1016/j.ccr.2014.02.025
13.Frederick, L., Eley, G., Wang, X. Y. & James, C. D. Analysis of genomic rearrangements associated with EGRFvIII expression suggests involvement of Alu repeat elements. Neuro. Oncol. 2, 159–63 (2000).
14.Heimberger, A. B. et al. Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin. Cancer Res. (2005). doi:10.1158/1078–0432.CCR–04–1737
15.Schmidt, M. H., Furnari, F. B., Cavenee, W. K. & Bogler, O. Epidermal growth factor receptor signaling intensity determines intracellular protein interactions, ubiquitination, and internalization. Proc Natl Acad Sci U S A 100, 6505–6510 (2003).
16.Gan, H. K., Kaye, A. H. & Luwor, R. B. The EGFRvIII variant in glioblastoma multiforme. J. Clin. Neurosci. 16, 748–754 (2009).
17.Ekstrand, A. J., Sugawa, N., James, C. D. & Collins, V. P. Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc. Natl. Acad. Sci. (2006). doi:10.1073/pnas.89.10.4309
18.Shinojima, N. et al. Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res 63, 6962–6970 (2003).
19.Wong, A. J. et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc. Natl. Acad. Sci. U.S. A. 89, 2965–9 (1992).
20.Ekstrand, A. J. et al. Genes for Epidermal Growth Factor Receptor, Transforming Growth Factor α, and Epidermal Growth Factor and Their Expression in Human Gliomas in Vivo. Cancer Res. (1991).
21.Libermann, T. A. et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature (1985). doi:10.1038/313144a0
22.Trippett, T. M. et al. Phase I and pharmacokinetic study of cetuximab and irinotecan in children with refractory solid tumors: A study of the pediatric oncology experimental therapeutic investigators’ consortium. J. Clin. Oncol. 27, 5102–5108 (2009).
23.Aldape, K. D. et al. Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance. J. Neuropathol. Exp. Neurol. (2004). doi:10.1093/jnen/63.7.700
24.Pelloski, C. E. et al. Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J. Clin. Oncol. (2007). doi:10.1200/JCO.2006.08.0705
25.Del Vecchio, C. A. et al. EGFRvIII gene rearrangement is an early event in glioblastoma tumorigenesis and expression defines a hierarchy modulated by epigenetic mechanisms. Oncogene (2013). doi:10.1038/onc.2012.280
26.Su Huang, H. J. et al. The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling. J. Biol. Chem. 272, 2927–2935 (1997).
27.Han, W., Zhang, T., Yu, H., Foulke, J. G. & Tang, C. K. Hypophosphorylation of residue Y1045 leads to defective downregulation of EGFRvIII. Cancer Biol. Ther. 5, 1361–1368 (2006).
28.Grandal, M. V. et al. EGFRvIII escapes down-regulation due to impaired internalization and sorting to lysosomes. Carcinogenesis 28, 1408–1417 (2007).
29.Nishikawa, R. et al. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc. Natl. Acad. Sci. 91, 7727–7731 (1994).
30.Huang, P. H., Xu, A.M. & White, F. M. Oncogenic EGFR Signaling Networks in Glioma. Sci. Signal. 2, re6–re6 (2009).
31.Gan, H. K., Cvrljevic, A. N. & Johns, T. G. The epidermal growth factor receptor variant III (EGFRvIII): Where wild things are altered. FEBS J. 280, 5350–5370 (2013).
32.Fuller, G. N. & Bigner, S. H. Amplified cellular oncogenes in neoplasms of the human central nervous system. Mutat. Res. Genet. Toxicol. 276, 299–306 (1992).
33.Brandao, M., Simon, T., Critchley, G. & Giamas, G. Astrocytes, the rising stars of the glioblastoma microenvironment. Glia 67, 779–790 (2019).
34.Nakod, P. S., Kim, Y. & Rao, S. S. Biomimetic models to examine microenvironmental regulation of glioblastoma stem cells. Cancer Letters (2018). doi:10.1016/j.canlet.2018.05.007
35.Herrera-Perez, M., Voytik-Harbin, S. L. & Rickus, J. L. Extracellular Matrix Properties Regulate the Migratory Response of Glioblastoma Stem Cells in Three-Dimensional Culture. Tissue Eng. Part A (2015). doi:10.1089/ten.tea.2014.0504
36.Ridet, J. L., Malhotra, S. K., Privat, A. & Gage, F. H. Reactive astrocytes: Cellular and molecular cues to biological function. Trends in Neurosciences (1997). doi:10.1016/S0166–2236(97)01139–9
37.Seike, T. et al. Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis. Clin. Exp. Metastasis (2011). doi:10.1007/s10585–010–9354–8
38.Jarzabek, M. A. et al. Molecular imaging in the development of a novel treatment paradigm for glioblastoma (GBM): An integrated multidisciplinary commentary. Drug Discovery Today (2013). doi:10.1016/j.drudis.2013.06.004
39.Sofroniew, M. V. & Vinters, H. V. Astrocytes: Biology and pathology. Acta Neuropathol. 119, 7–35 (2010).
40.Placone, A. L., Quiñones-Hinojosa, A. & Searson, P. C. The role of astrocytes in the progression of brain cancer: complicating the picture of the tumor microenvironment. Tumor Biology 37, (2016).
41.Oushy, S. et al. Glioblastoma multiforme-derived extracellular vesicles drive normal astrocytes towards a tumour-enhancing phenotype. Philos. Trans. R. Soc. B Biol. Sci. (2018). doi:10.1098/rstb.2016.0477
42.Zamanian, J. L. et al. Genomic Analysis of Reactive Astrogliosis. J. Neurosci. (2012). doi:10.1523/JNEUROSCI.6221–11.2012
43.Lee, J., Borboa, A. K., Baird, A. & Eliceiri, B. P. Non-invasive quantification of brain tumor-induced astrogliosis. BMC Neurosci. (2011). doi:10.1186/1471–2202–12–9
44.Rath, B. H., Fair, J. M., Jamal, M., Camphausen, K. & Tofilon, P. J. Astrocytes Enhance the Invasion Potential of Glioblastoma Stem-Like Cells. PLoS One (2013). doi:10.1371/journal.pone.0054752
45.Skog, J. et al. Glioblastoma microvesicles transport RNA and protein that promote promote tumor growth and provide diagnostic biomarkers Johan. Nat. Cell Biol. 10, 1470–1476 (2012).
46.Yáñez-Mó, M. et al. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. vesicles (2015). doi:10.3402/jev.v4.27066
47.Hessvik, N. P. & Llorente, A. Current knowledge on exosome biogenesis and release. Cell. Mol. Life Sci. 75, 193–208 (2018).
48.Al-Nedawi, K. et al. Intercellular transfer of the oncogenic receptor EGFRviii by microvesicles derived from tumor cells. Nat. Cell Biol. 10, 619–624 (2008).
49.Pan, B. T., Teng, K., Wu, C., Adam, M. & Johnstone, R. M. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J. Cell Biol. 101, 942–948 (1985).
50.Eden, E. R., Huang, F., Sorkin, A. & Futter, C. E. The Role of EGF Receptor Ubiquitination in Regulating Its Intracellular Traffic. Traffic 13, 329–337 (2012).
51.Raiborg, C. & Stenmark, H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458, 445–52 (2009).
52.Sun, W. et al. Cell-Free Reconstitution of Multivesicular Body Formation and Receptor Sorting. Traffic 11, 867–876 (2010).
53.Gireud-Goss, M. et al. Distinct mechanisms enable inward or outward budding from late endosomes/multivesicular bodies. Exp. Cell Res. (2018). doi:10.1016/J.YEXCR.2018.08.027
54.Zage, P. E. et al. UBE4B levels are correlated with clinical outcomes in neuroblastoma patients and with altered neuroblastoma cell proliferation and sensitivity to epidermal growth factor receptor inhibitors. Cancer 119, 915–23 (2013).
55.Levkowitz, G. et al. c-Cb1/Sli–1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor. Genes Dev. (1998). doi:10.1101/gad.12.23.3663
56.Levkowitz, G. et al. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli–1. Mol. Cell (1999). doi:10.1016/S1097–2765(00)80231–2
57.Longva, K. E. et al. Ubiquitination and proteasomal activity is required for transport of the EGF receptor to inner membranes of multivesicular bodies. J. Cell Biol. (2002). doi:10.1083/jcb.200106056
58.Waterman, H. A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling. EMBO J. (2002). doi:10.1093/emboj/21.3.303
59.Sigismund, S. et al. Clathrin-Mediated Internalization Is Essential for Sustained EGFR Signaling but Dispensable for Degradation. Dev. Cell 15, 209–219 (2008).
60.Trajkovic, K. et al. Ceramide Triggers Budding of Exosome Vesicles into Multivesicular Endosomes. Science (80-.). 316, 715–719 (2007).
61.Babst, M. MVB Vesicle Formation, ESCRT-Dependent, ESCRT-Independent, and Everything in Between. 23, 452–457 (2011).
62.Möbius, W. et al. Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway. Traffic (2003). doi:10.1034/j.1600–0854.2003.00072.x
63.Raposo, G. & Stoorvogel, W. Extracellular vesicles: Exosomes, microvesicles, and friends. J. Cell Biol. 200, 373–383 (2013).
64.Kowal, J., Tkach, M. & Théry, C. Biogenesis and secretion of exosomes. Current Opinion in Cell Biology 29, (2014).
65.Théry, C., Amigorena, S., Raposo, G. & Clayton, A. Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids. in Current Protocols in Cell Biology (John Wiley & Sons, Inc., 2001). doi:10.1002/0471143030.cb0322s30
66.Zeineldin, R., Ning, Y. & Hudson, L. G. The constitutive activity of epidermal growth factor receptor vIII leads to activation and differential trafficking of wild-type epidermal growth factor receptor and erbB2. J. Histochem. Cytochem. 58, 529–41 (2010).
67.Manini, I. et al. Role of microenvironment in glioma invasion: What we learned from in vitro models. International Journal of Molecular Sciences (2018). doi:10.3390/ijms19010147
68.Nagane, M. et al. A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. Cancer Res. 56, 5079–5086 (1996).
69.Grandal, M. V et al. EGFRvIII escapes down-regulation due to impaired internalization and sorting to lysosomes. 28, 1408–1417 (2007).
70.Al-Nedawi, K. et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol. 10, 619–624 (2008).
71.Karim, M. A., Samyn, D. R., Mattie, S. & Brett, C. L. Distinct features of multivesicular body-lysosome fusion revealed by a new cell-free content-mixing assay. Traffic (2018). doi:10.1111/tra.12543
72.Luzio, J. P. et al. Lysosome-endosome fusion and lysosome biogenesis. J. Cell Sci. (2000).
73.Luzio, J. P., Gray, S. R. & Bright, N. A. Endosome-lysosome fusion. Biochem. Soc. Trans. (2010). doi:10.1042/bst0381413
74.Piper, R. C. & Katzmann, D. J. Biogenesis and Function of Multivesicular Bodies. Annu. Rev. Cell Dev. Biol. (2007). doi:10.1146/annurev.cellbio.23.090506.123319
75.Mathieu, M., Martin-Jaular, L., Lavieu, G. & Théry, C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat. Cell Biol. 21, 9–17 (2019).
76.Willms, E. et al. Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci. Rep. 6, 22519 (2016).