Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression

Journal of Clinical Investigation

Volumn 124, Issue 7, 2014, Pages 2861-2876

  Ferrarese, Roberto ^a   Harsh IV, Griffith R ^b   Yadav, Ajay K ^c   Bug, Eva ^a   Maticzka, Daniel ^a   Reichardt, Wilfried ^a   Dombrowski, Stephen M ^d   Miller, Tyler E ^e   Masilamani, Anie P ^a   Dai, Fangping ^a   Kim, Hyunsoo ^f   Hadler, Michael ^a   Scholtens, Denise M ^g   Yu, Irene L Y ^a   Beck, Jürgen ^a   Srinivasasainagendra, Vinodh ^f   Costa, Fabrizio ^a   Baxan, Nicoleta ^a   Pfeifer, Dietmar ^a   Von Elverfeldt, Dominik ^a   Backofen, Rolf ^a   Weyerbrock, Astrid ^a   Duarte, Christine W ^h   He, Xiaolin ^g   Prinz, Marco ^a   Chandler, James P ^g   Vogel, Hannes ^b   Chakravarti, Arnab ⁱ   Rich, Jeremy N ^e   Carro, Maria S ^a   Bredel, Markus ^a,b,f,j   more..

^a UNIVERSITY OF FREIBURG   (Germany)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF DELHI   (India)

^d Department of Neurological Surgery Section of Pediatric and Congenital Neurosurgery   (United States)

^e LERNER RESEARCH INSTITUTE   (United States)

^f UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^g NORTHWESTERN UNIVERSITY   (United States)

^h Maine Medical Center Research Institute   (United States)

ⁱ OHIO STATE UNIVERSITY   (United States)

^j The University of Alabama at Birmingham   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; CD31 ANTIGEN; EARLY ENDOSOME ANTIGEN 1; EPIDERMAL GROWTH FACTOR RECEPTOR; MICRORNA 124; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; POLYPYRIMIDINE TRACT BINDING PROTEIN; POLYPYRIMIDINE TRACT BINDING PROTEIN 1; SOMATOMEDIN B RECEPTOR; SYNEXIN; UNCLASSIFIED DRUG;

ALTERNATIVE RNA SPLICING; ANGIOGENESIS; ARTICLE; CELL LINEAGE; COPY NUMBER VARIATION; EXON; GENE AMPLIFICATION; GENE MUTATION; GENE OVEREXPRESSION; GENE REPRESSION; GLIOBLASTOMA; HUMAN; HUMAN TISSUE; MOUSE; NERVE CELL DIFFERENTIATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; TUMOR GROWTH;

ALTERNATIVE SPLICING; ANNEXIN A7; BRAIN NEOPLASMS; CELL LINEAGE; CELL TRANSFORMATION, NEOPLASTIC; DISEASE PROGRESSION; EXONS; GENE KNOCKDOWN TECHNIQUES; GLIOBLASTOMA; HETEROGENEOUS-NUCLEAR RIBONUCLEOPROTEINS; HUMANS; MICRORNAS; NEOPLASTIC STEM CELLS; NEOVASCULARIZATION, PATHOLOGIC; POLYPYRIMIDINE TRACT-BINDING PROTEIN; RECEPTOR, EPIDERMAL GROWTH FACTOR; RNA, MESSENGER; RNA, NEOPLASM; SIGNAL TRANSDUCTION; TUMOR CELLS, CULTURED;

EID: 84903778038     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI68836     Document Type: Article

References (97)

1. Parsons DW, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321(5897):1807-1812.
2. Bredel M, et al. A network model of a cooperative genetic landscape in brain tumors. JAMA. 2009;302(3):261-275.
3. Verhaak RG, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1):98-110.
4. McLendon R, Friedman A, Bigner DD, Van Meir EG. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455(7216):1061-1068.
5. Wong AJ, Bigner SH, Bigner DD, Kinzler KW, Hamilton SR, Vogelstein B. Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci U S A. 1987;84(19):6899-6903.
6. Bredel M, et al. NFKBIA deletion in glioblastomas. N Engl J Med. 2011;364(7):627-637.
7. Vivanco I, et al. The phosphatase and tensin homolog regulates epidermal growth factor receptor (EGFR) inhibitor response by targeting EGFR for degradation. Proc Natl Acad Sci U S A. 2010;107(14):6459-6464.
8. Yadav AK, et al. Monosomy of chromosome 10 associated with dysregulation of epidermal growth factor signaling in glioblastomas. JAMA. 2009;302(3):276-289.
9. Nilsen TW, Graveley BR. Expansion of the eukaryotic proteome by alternative splicing. Nature. 2010;463(7280):457-463.
10. Wang ET, et al. Alternative isoform regulation in human tissue transcriptomes. Nature. 2008;456(7221):470-476. (Pubitemid 352759009)
11. Keren H, Lev-Maor G, Ast G. Alternative splicing and evolution: diversification, exon definition and function. Nat Rev Genet. 2010;11(5):345-355.
12. Venables JP, et al. Cancer-associated regulation of alternative splicing. Nat Struct Mol Biol. 2009;16(6):670-676.
13. Xu Q, Lee C. Discovery of novel splice forms and functional analysis of cancer-specific alternative splicing in human expressed sequences. Nucleic Acids Res. 2003;31(19):5635-5643. (Pubitemid 37441935)
14. Ghigna C, et al. Cell motility is controlled by SF2/ ASF through alternative splicing of the Ron protooncogene. Mol Cell. 2005;20(6):881-890. (Pubitemid 41814877)
15. Liu J, et al. Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events. Genome Res. 2012;22(12):2315-2327.
16. Narla G, et al. A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk. Cancer Res. 2005;65(4):1213-1222. (Pubitemid 40270146)
17. Klinck R, et al. Multiple alternative splicing markers for ovarian cancer. Cancer Res. 2008;68(3):657-663. (Pubitemid 351206740)
18. Venables JP, et al. Identification of alternative splicing markers for breast cancer. Cancer Res. 2008; 68(22):9525-9531.
19. French PJ, et al. Identification of differentially regulated splice variants and novel exons in glial brain tumors using exon expression arrays. Cancer Res. 2007;67(12):5635-5642. (Pubitemid 46984994)
20. Golan-Gerstl R, et al. Splicing factor hnRNP A2/B1 regulates tumor suppressor gene splicing and is an oncogenic driver in glioblastoma. Cancer Res. 2011; 71(13):4464-4472.
21. Sugawa N, Ekstrand AJ, James CD, Collins VP. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci U S A. 1990;87(21):8602-8606.
22. Wong AJ, et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci U S A. 1992;89(7):2965-2969.
23. Buljan M, et al. Tissue-specific splicing of disordered segments that embed binding motifs rewires protein interaction networks. Mol Cell. 2012; 46(6):871-883.
24. Ellis JD, et al. Tissue-specific alternative splicing remodels protein-protein interaction networks. Mol Cell. 2012;46(6):884-892.
25. Prinos P, et al. Alternative splicing of SYK regulates mitosis and cell survival. Nat Struct Mol Biol. 2011; 18(6):673-679.
26. Kalsotra A, Cooper TA. Functional consequences of developmentally regulated alternative splicing. Nat Rev Genet. 2011;12(10):715-729.
27. Gabut M, et al. An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Cell. 2011;147(1):132-146.
28. Ungewitter E, Scrable H. Delta40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs. Genes Dev. 2010; 24(21):2408-2419.
29. Yang Z, Sui Y, Xiong S, Liour SS, Phillips AC, Ko L. Switched alternative splicing of oncogene CoAA during embryonal carcinoma stem cell differentiation. Nucleic Acids Res. 2007;35(6):1919-1932. (Pubitemid 47061660)
30. Yeo GW, Van Nostrand E, Holste D, Poggio T, Burge CB. Identification and analysis of alternative splicing events conserved in human and mouse. Proc Natl Acad Sci U S A. 2005;102(8):2850-2855.
31. Fagnani M, et al. Functional coordination of alternative splicing in the mammalian central nervous system. Genome Biol. 2007;8(6):R108.
32. Ule J, et al. Nova regulates brain-specific splicing to shape the synapse. Nat Genet. 2005;37(8):844-852. (Pubitemid 41077110)
33. Calarco JA, et al. Regulation of vertebrate nervous system alternative splicing and development by an SR-related protein. Cell. 2009;138(5):898-910.
34. Raj B, et al. Cross-regulation between an alternative splicing activator and a transcription repressor controls neurogenesis. Mol Cell. 2011;43(5):843-850.
35. Srivastava M, et al. Haploinsufficiency of Anx7 tumor suppressor gene and consequent genomic instability promotes tumorigenesis in the Anx7+/-mouse. Proc Natl Acad Sci U S A. 2003; 100(24):14287-14292. (Pubitemid 37499229)
36. Srivastava M, et al. ANX7, a candidate tumor suppressor gene for prostate cancer. Proc Natl Acad Sci U S A. 2001;98(8):4575-4580. (Pubitemid 32295018)
37. Morel E, Parton RG, Gruenberg J. Annexin A2-dependent polymerization of actin mediates endosome biogenesis. Dev Cell. 2009;16(3):445-457.
38. Rescher U, Ruhe D, Ludwig C, Zobiack N, Gerke V. Annexin 2 is a phosphatidylinositol (4,5)-bisphosphate binding protein recruited to actin assem-bly sites at cellular membranes. J Cell Sci. 2004; 117(pt 16):3473-3480.
39. Goebeler V, Poeter M, Zeuschner D, Gerke V, Rescher U. Annexin A8 regulates late endosome organization and function. Mol Biol Cell. 2008; 19(12):5267-5278.
40. White IJ, Bailey LM, Aghakhani MR, Moss SE, Futter CE. EGF stimulates annexin 1-dependent inward vesiculation in a multivesicular endosome subpopulation. EMBO J. 2006;25(1):1-12. (Pubitemid 43077290)
41. Rick M, Ramos Garrido SI, Herr C, Thal DR, Noegel AA, Clemen CS. Nuclear localization of Annexin A7 during murine brain development. BMC Neurosci. 2005;6:25.
42. Magendzo K, Shirvan A, Cultraro C, Srivastava M, Pollard HB, Burns AL. Alternative splicing of human synexin mRNA in brain, cardiac, and skeletal muscle alters the unique N-terminal domain. J Biol Chem. 1991;266(5):3228-3232. (Pubitemid 21909198)
43. Burns AL, et al. Calcium channel activity of purified human synexin and structure of the human synexin gene. Proc Natl Acad Sci U S A. 1989; 86(10):3798-3802.
44. Makeyev EV, Zhang J, Carrasco MA, Maniatis T. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell. 2007;27(3):435-448. (Pubitemid 47126944)
45. Boutz PL, et al. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev. 2007;21(13):1636-1652. (Pubitemid 47026368)
46. McCutcheon IE, Hentschel SJ, Fuller GN, Jin W, Cote GJ. Expression of the splicing regulator polypyrimidine tract-binding protein in normal and neoplastic brain. Neuro Oncol. 2004;6(1):9-14. (Pubitemid 38139633)
47. Cheung HC, Corley LJ, Fuller GN, McCutcheon IE, Cote GJ. Polypyrimidine tract binding protein and Notch1 are independently re-expressed in glioma. Mod Pathol. 2006;19(8):1034-1041. (Pubitemid 44106718)
48. Liu C, et al. Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell. 2011; 146(2):209-221.
49. Peng SC, Lai YT, Huang HY, Huang HD, Huang YS. A novel role of CPEB3 in regulating EGFR gene transcription via association with Stat5b in neurons. Nucleic Acids Res. 2010;38(21):7446-7457.
50. Wagner B, Natarajan A, Grunaug S, Kroismayr R, Wagner EF, Sibilia M. Neuronal survival depends on EGFR signaling in cortical but not midbrain astrocytes. EMBO J. 2006;25(4):752-762. (Pubitemid 43292437)
51. Aguirre A, Rubio ME, Gallo V. Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal. Nature. 2010; 467(7313):323-327.
52. Lill NL, Sever NI. Where EGF receptors transmit their signals. Sci Signal. 2012;5(243):pe41.
53. Cartegni L, Chew SL, Krainer AR. Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet. 2002; 3(4):285-298. (Pubitemid 34279797)
54. Woolfe A, Mullikin JC, Elnitski L. Genomic features defining exonic variants that modulate splicing. Genome Biol. 2010;11(2):R20.
55. Liu HX, Cartegni L, Zhang MQ, Krainer AR. A mechanism for exon skipping caused by nonsense or missense mutations in BRCA1 and other genes. Nat Genet. 2001;27(1):55-58. (Pubitemid 32044518)
56. Cheung HC, et al. Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays. BMC Genomics. 2008;9:216.
57. Zhang C, et al. Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2. Genes Dev. 2008;22(18):2550-2563.
58. Goo YH, Cooper TA. CUGBP2 directly interacts with U2 17S snRNP components and promotes U2 snRNA binding to cardiac troponin T pre-mRNA. Nucleic Acids Res. 2009;37(13):4275-4286.
59. Spellman R, Llorian M, Smith CW. Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1. Mol Cell. 2007;27(3):420-434. (Pubitemid 47126939)
60. Llorian M, et al. Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. Nat Struct Mol Biol. 2010;17(9):1114-1123.
61. Xue Y, et al. Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping. Mol Cell. 2009;36(6):996-1006
62. Maticzka D, Lange SJ, Costa F, Backofen R. Graph-Prot: modeling binding preferences of RNA-binding proteins. Genome Biol. 2014;15(1):R17.
63. Reid DC, Chang BL, Gunderson SI, Alpert L, Thompson WA, Fairbrother WG. Next-generation SELEX identifies sequence and structural determinants of splicing factor binding in human pre-mRNA sequence. RNA. 2009;15(12):2385-2397
64. Xue Y, et al. Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell. 2013;152(1-2):82-96.
65. O'Neill RA, et al. Isoelectric focusing technology quantifies protein signaling in 25 cells. Proc Natl Acad Sci U S A. 2006;103(44):16153-16158. (Pubitemid 44717502)
66. Cheung HC, et al. Splicing factors PTBP1 and PTBP2 promote proliferation and migration of glioma cell lines. Brain. 2009;132(pt 8):2277-2288
67. Ocharoenrat P, et al. Epidermal growth factor-like ligands differentially up-regulate matrix metalloproteinase 9 in head neck squamous carcinoma cells. Cancer Res. 2000;60(4):1121-1128.
68. Lu KV, et al. VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex. Cancer Cell. 2012;22(1):21-35.
69. Kunkel P, et al. Inhibition of glioma angiogenesis and growth in vivo by systemic treatment with a monoclonal antibody against vascular endothelial growth factor receptor-2. Cancer Res. 2001; 61(18):6624-6628. (Pubitemid 32896475)
70. Plate KH, Breier G, Weich HA, Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature. 1992;359(6398):845-848.
71. Goldman CK, Kim J, Wong WL, King V, Brock T, Gillespie GY. Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology. Mol Biol Cell. 1993;4(1):121-133. (Pubitemid 23071308)
72. Cheng SY, et al. Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor. Proc Natl Acad Sci U S A. 1996;93(16):8502-8507.
73. Pore N, Liu S, Haas-Kogan DA, O'Rourke DM, Maity A. PTEN mutation and epidermal growth factor receptor activation regulate vascular endothelial growth factor (VEGF) mRNA expression in human glioblastoma cells by transactivating the proximal VEGF promoter. Cancer Res. 2003;63(1):236-241. (Pubitemid 36070445)
74. Maity A, Pore N, Lee J, Solomon D, O'Rourke DM. Epidermal growth factor receptor transcriptionally up-regulates vascular endothelial growth factor expression in human glioblastoma cells via a pathway involving phosphatidylinositol 3′-kinase and distinct from that induced by hypoxia. Cancer Res. 2000;60(20):5879-5886.
75. Ricci-Vitiani L, et al. Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature. 2010;468(7325):824-828.
76. Cheng L, et al. Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell. 2013;153(1):139-152.
77. Jin X, et al. EGFR-AKT-Smad signaling promotes formation of glioma stem-like cells and tumor angiogenesis by ID3-driven cytokine induction. Cancer Res. 2011;71(22):7125-7134.
78. Bonavia R, et al. EGFRvIII promotes glioma B, interleukin-8 pathway.?angiogenesis and growth through the NF-Oncogene. 2012;31(36):4054-4066.
79. Arnaoutova I, Kleinman HK. In vitro angiogenesis: endothelial cell tube formation on gelled basement membrane extract. Nat Protoc. 2010;5(4):628-635.
80. Cheng LC, Pastrana E, Tavazoie M, Doetsch F. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci. 2009; 12(4):399-408.
81. Silber J, et al. miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells induce differentiation of brain tumor stem cells. BMC Med. 2008;6:14.
82. Lang MF, et al. Genome-wide profiling identified a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. PLoS One. 2012;7(4):e36248.
83. Fowler A, et al. miR-124a is frequently down-regulated in glioblastoma is involved in migration invasion. Eur J Cancer. 2011;47(6):953-963
84. Xia H, et al. Loss of brain-enriched miR-124 microRNA enhances stem-like traits invasiveness of glioma cells. J Biol Chem. 2012;287(13):9962-9971.
85. Zhu H, et al. Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis. Proc Natl Acad Sci U S A. 2009; 106(8):2712-2716.
86. Xing Y, Lee CJ. Protein modularity of alternatively spliced exons is associated with tissue-specific regulation of alternative splicing. PLoS Genet. 2005; 1(3):e34.
87. Nunes MC, et al. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med. 2003;9(4):439-447. (Pubitemid 36460078)
88. Auvergne RM, et al. Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes. Cell Rep. 2013;3(6):2127-2141.
89. Sanai N, Alvarez-Buylla A, Berger MS. Neural stem cells and the origin of gliomas. N Engl J Med. 2005;353(8):811-822.
90. Galli R, et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 2004; 64(19):7011-7021 (Pubitemid 39331011)
91. Alcantara Llaguno S, et al. Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell. 2009;15(1):45-56.
92. Wang R, et al. Glioblastoma stem-like cells give rise to tumour endothelium. Nature. 2010; 468(7325):829-833.
93. Pen A, Moreno MJ, Martin J, Stanimirovic DB. Molecular markers of extracellular matrix remodeling in glioblastoma vessels: microarray study of laser-captured glioblastoma vessels. Glia. 2007; 55(6):559-572. (Pubitemid 46474298)
94. Conaco C, Otto S, Han JJ, Mandel G. Reciprocal actions of REST and a microRNA promote neuronal identity. Proc Natl Acad Sci U S A. 2006; 103(7):2422-2427. (Pubitemid 43271685)
95. Li Q, et al. The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation. Elife. 2014;3:e01201.
96. Licatalosi DD, et al. Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain. Genes Dev. 2012; 26(14):1626-1642.
97. Carro MS, et al. The transcriptional network for mesenchymal transformation of brain tumours. Nature. 2010;463(7279):318-325.