Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells

Oncotarget

Volumn 7, Issue 25, 2016, Pages 38638-38657

  Corsaro, Alessandro ^a   Bajetto, Adriana ^a   Thellung, Stefano ^a   Begani, Giulia ^a   Villa, Valentina ^a   Nizzari, Mario ^a   Pattarozzi, Alessandra ^a   Solari, Agnese ^a   Gatti, Monica ^a   Pagano, Aldo ^a,b   Würth, Roberto ^a   Daga, Antonio ^b   Barbieri, Federica ^a   Florio, Tullio ^a  

^a UNIVERSITY OF GENOA   (Italy)

^b UNIVERSITY OF GENOA   (Italy)

Author keywords

Cancer stem cells; GFAP; Glioblastoma; In vivo tumorigenicity; Prion protein

Indexed keywords

PRION PROTEIN; SHORT HAIRPIN RNA; TRANSCRIPTION FACTOR NANOG; TRANSCRIPTION FACTOR SOX2;

ARTICLE; CANCER RECURRENCE; CANCER STEM CELL; CARCINOGENICITY; CELL COUNT; CELL DEATH; CELL GROWTH; CELL PROLIFERATION; CELL SELF-RENEWAL; CELL SUBPOPULATION; CELL VIABILITY; DNA SYNTHESIS; DOWN REGULATION; ENDOTHELIUM CELL; GENE SILENCING; GLIOBLASTOMA; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOREACTIVITY; PHENOTYPE; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN FUNCTION; ANIMAL; CELL DIFFERENTIATION; GENETIC TRANSFECTION; GENETICS; METABOLISM; MOUSE; NONOBESE DIABETIC MOUSE; PATHOLOGY; SCID MOUSE; TUMOR CELL LINE;

ANIMALS; CELL DIFFERENTIATION; CELL LINE, TUMOR; CELL PROLIFERATION; GLIOBLASTOMA; HUMANS; MICE; MICE, INBRED NOD; MICE, SCID; NEOPLASTIC STEM CELLS; PRION PROTEINS; TRANSFECTION;

EID: 84978038888     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.9575     Document Type: Article

References (90)

1. Prusiner SB. Prions. Proceedings of the National Academy of Sciences of the United States of America. 1998; 95:13363-13383.
2. Corsaro A, Thellung S, Villa V, Nizzari M and Florio T. Role of prion protein aggregation in neurotoxicity. Int J Mol Sci. 2012; 13:8648-8669.
3. Aguzzi A and Falsig J. Prion propagation, toxicity and degradation. Nature neuroscience. 2012; 15:936-939.
4. Corsaro A, Thellung S, Bucciarelli T, Scotti L, Chiovitti K, Villa V, D'Arrigo C, Aceto A and Florio T. High hydrophobic amino acid exposure is responsible of the neurotoxic effects induced by E200K or D202N diseaserelated mutations of the human prion protein. Int J Biochem Cell Biol. 2011; 43:372-382.
5. Corsaro A, Thellung S, Villa V, Principe DR, Paludi D, Arena S, Millo E, Schettini D, Damonte G, Aceto A, Schettini G and Florio T. Prion protein fragment 106-126 induces a p38 MAP kinase-dependent apoptosis in SH-SY5Y neuroblastoma cells independently from the amyloid fibril formation. Ann N Y Acad Sci. 2003; 1010:610-622.
6. Thellung S, Corsaro A, Villa V, Simi A, Vella S, Pagano A and Florio T. Human PrP90-231-induced cell death is associated with intracellular accumulation of insoluble and protease-resistant macroaggregates and lysosomal dysfunction. Cell Death and Disease. 2011; 2:e138. doi: 10.1038/cddis.2011.21.
7. Thellung S, Gatta E, Pellistri F, Corsaro A, Villa V, Vassalli M, Robello M and Florio T. Excitotoxicity through NMDA receptors mediates cerebellar granule neuron apoptosis induced by prion protein 90-231 fragment. Neurotox Res. 2013; 23:301-314.
8. Thellung S, Villa V, Corsaro A, Pellistri F, Venezia V, Russo C, Aceto A, Robello M and Florio T. ERK1/2 and p38 MAP kinases control prion protein fragment 90-231-induced astrocyte proliferation and microglia activation. Glia. 2007; 55:1469-1485.
9. Cohen FE and Prusiner SB. Pathologic conformations of prion proteins. Annu Rev Biochem. 1998; 67:793-819.
10. Corsaro A, Paludi D, Villa V, D'Arrigo C, Chiovitti K, Thellung S, Russo C, Di Cola D, Ballerini P, Patrone E, Schettini G, Aceto A and Florio T. Conformation dependent pro-apoptotic activity of the recombinant human prion protein fragment 90-231. Int J Immunopathol Pharmacol. 2006; 19:339-356.
11. Prusiner SB. Biology and genetics of prions causing neurodegeneration. Annual review of genetics. 2013; 47:601-623.
12. Prusiner SB. Molecular biology of prion diseases. Science. 1991; 252:1515-1522.
13. Watts JC and Prusiner SB. Mouse models for studying the formation and propagation of prions. The Journal of biological chemistry. 2014; 289:19841-19849.
14. Aguzzi A, Nuvolone M and Zhu C. The immunobiology of prion diseases. Nature reviews Immunology. 2013; 13:888-902.
15. Weissmann C and Flechsig E. PrP knock-out and PrP transgenic mice in prion research. Br Med Bull. 2003; 66:43-60.
16. McLennan NF, Brennan PM, McNeill A, Davies I, Fotheringham A, Rennison KA, Ritchie D, Brannan F, Head MW, Ironside JW, Williams A and Bell JE. Prion protein accumulation and neuroprotection in hypoxic brain damage. The American journal of pathology. 2004; 165:227-235.
17. Brown DR, Schulz-Schaeffer WJ, Schmidt B and Kretzschmar HA. Prion protein-deficient cells show altered response to oxidative stress due to decreased SOD-1 activity. Exp Neurol. 1997; 146:104-112.
18. Liang J, Pan Y, Zhang D, Guo C, Shi Y, Wang J, Chen Y, Wang X, Liu J, Guo X, Chen Z, Qiao T and Fan D. Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS. FASEB journal. 2007; 21:2247-2256.
19. Bremer J, Baumann F, Tiberi C, Wessig C, Fischer H, Schwarz P, Steele AD, Toyka KV, Nave KA, Weis J and Aguzzi A. Axonal prion protein is required for peripheral myelin maintenance. Nature neuroscience. 2010; 13:310-318.
20. Malaga-Trillo E, Solis GP, Schrock Y, Geiss C, Luncz L, Thomanetz V and Stuermer CA. Regulation of embryonic cell adhesion by the prion protein. PLoS Biol. 2009; 7:e55.
21. Mabbott N and Turner M. Prions and the blood and immune systems. Haematologica. 2005; 90:542-548.
22. Martin-Lanneree S, Hirsch TZ, Hernandez-Rapp J, Halliez S, Vilotte JL, Launay JM and Mouillet-Richard S. PrP(C) from stem cells to cancer. Frontiers in cell and developmental biology. 2014; 2:55.
23. Steele AD, Emsley JG, Ozdinler PH, Lindquist S and Macklis JD. Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103:3416-3421.
24. Zhang CC, Steele AD, Lindquist S and Lodish HF. Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their selfrenewal. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103:2184-2189.
25. Lima FR, Arantes CP, Muras AG, Nomizo R, Brentani RR and Martins VR. Cellular prion protein expression in astrocytes modulates neuronal survival and differentiation. J Neurochem. 2007; 103:2164-2176.
26. Lee YJ and Baskakov IV. Treatment with normal prion protein delays differentiation and helps to maintain high proliferation activity in human embryonic stem cells. J Neurochem. 2010; 114:362-373.
27. Panigaj M, Glier H, Wildova M and Holada K. Expression of prion protein in mouse erythroid progenitors and differentiating murine erythroleukemia cells. PloS one. 2011; 6:e24599.
28. Santos TG, Silva IR, Costa-Silva B, Lepique AP, Martins VR and Lopes MH. Enhanced neural progenitor/stem cells self-renewal via the interaction of stress-inducible protein 1 with the prion protein. Stem Cells. 2011; 29:1126-1136.
29. Stella R, Massimino ML, Sandri M, Sorgato MC and Bertoli A. Cellular prion protein promotes regeneration of adult muscle tissue. Mol Cell Biol. 2010; 30:4864-4876.
30. Mouillet-Richard S, Ermonval M, Chebassier C, Laplanche JL, Lehmann S, Launay JM and Kellermann O. Signal transduction through prion protein. Science. 2000; 289:1925-1928.
31. Santos TG, Lopes MH and Martins VR. Targeting prion protein interactions in cancer. Prion. 2015; 9:165-173.
32. Comincini S. Searching for molecular markers of human gliomas. Functional neurology. 2001; 16:291-298.
33. Lopes MH, Santos TG, Rodrigues BR, Queiroz-Hazarbassanov N, Cunha IW, Wasilewska-Sampaio AP, Costa-Silva B, Marchi FA, Bleggi-Torres LF, Sanematsu PI, Suzuki SH, Oba-Shinjo SM, Marie SK, Toulmin E, Hill AF and Martins VR. Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival. Oncogene. 2015; 34:3305-3314.
34. Du J, Pan Y, Shi Y, Guo C, Jin X, Sun L, Liu N, Qiao T and Fan D. Overexpression and significance of prion protein in gastric cancer and multidrug-resistant gastric carcinoma cell line SGC7901/ADR. International journal of cancer. 2005; 113:213-220.
35. Diarra-Mehrpour M, Arrabal S, Jalil A, Pinson X, Gaudin C, Pietu G, Pitaval A, Ripoche H, Eloit M, Dormont D and Chouaib S. Prion protein prevents human breast carcinoma cell line from tumor necrosis factor alpha-induced cell death. Cancer research. 2004; 64:719-727.
36. Mehrpour M and Codogno P. Prion protein: From physiology to cancer biology. Cancer Lett. 2010; 290:1-23.
37. Du L, Rao G, Wang H, Li B, Tian W, Cui J, He L, Laffin B, Tian X, Hao C, Liu H, Sun X, Zhu Y, Tang DG, Mehrpour M, Lu Y, et al. CD44-positive cancer stem cells expressing cellular prion protein contribute to metastatic capacity in colorectal cancer. Cancer research. 2013; 73:2682-2694.
38. Liang J, Luo G, Ning X, Shi Y, Zhai H, Sun S, Jin H, Liu Z, Zhang F, Lu Y, Zhao Y, Chen X, Zhang H, Guo X, Wu K and Fan D. Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein. Biochem Cell Biol. 2007; 85:375-383.
39. Pan Y, Zhao L, Liang J, Liu J, Shi Y, Liu N, Zhang G, Jin H, Gao J, Xie H, Wang J, Liu Z and Fan D. Cellular prion protein promotes invasion and metastasis of gastric cancer. FASEB journal. 2006; 20:1886-1888.
40. Adorno-Cruz V, Kibria G, Liu X, Doherty M, Junk DJ, Guan D, Hubert C, Venere M, Mulkearns-Hubert E, Sinyuk M, Alvarado A, Caplan AI, Rich J, Gerson SL, Lathia J and Liu H. Cancer stem cells: targeting the roots of cancer, seeds of metastasis, and sources of therapy resistance. Cancer research. 2015; 75:924-929.
41. Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F and Vescovi A. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer research. 2004; 64:7011-7021.
42. Eramo A, Ricci-Vitiani L, Zeuner A, Pallini R, Lotti F, Sette G, Pilozzi E, Larocca LM, Peschle C and De Maria R. Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ. 2006; 13:1238-1241.
43. Florio T and Barbieri F. The status of the art of human malignant glioma management: the promising role of targeting tumor-initiating cells. Drug discovery today. 2012; 17:1103-1110.
44. Wurth R, Barbieri F and Florio T. New molecules and old drugs as emerging approaches to selectively target human glioblastoma cancer stem cells. BioMed research international. 2014; 2014:126586.
45. Wurth R, Thellung S, Bajetto A, Mazzanti M, Florio T and Barbieri F. Drug-repositioning opportunities for cancer therapy: novel molecular targets for known compounds. Drug discovery today. 2016; 21:190-199.
46. Griffero F, Daga A, Marubbi D, Capra MC, Melotti A, Pattarozzi A, Gatti M, Bajetto A, Porcile C, Barbieri F, Favoni RE, Lo Casto M, Zona G, Spaziante R, Florio T and Corte G. Different response of human glioma tumorinitiating cells to epidermal growth factor receptor kinase inhibitors. The Journal of biological chemistry. 2009; 284:7138-7148.
47. Bajetto A, Porcile C, Pattarozzi A, Scotti L, Aceto A, Daga A, Barbieri F and Florio T. Differential role of EGF and BFGF in human GBM-TIC proliferation: relationship to EGFR-tyrosine kinase inhibitor sensibility. Journal of biological regulators and homeostatic agents. 2013; 27:143-154.
48. Gatti M, Pattarozzi A, Bajetto A, Wurth R, Daga A, Fiaschi P, Zona G, Florio T and Barbieri F. Inhibition of CXCL12/CXCR4 autocrine/paracrine loop reduces viability of human glioblastoma stem-like cells affecting self-renewal activity. Toxicology. 2013; 314:209-220.
49. Wurth R, Pattarozzi A, Gatti M, Bajetto A, Corsaro A, Parodi A, Sirito R, Massollo M, Marini C, Zona G, Fenoglio D, Sambuceti G, Filaci G, Daga A, Barbieri F and Florio T. Metformin selectively affects human glioblastoma tumor-initiating cell viability: A role for metformin-induced inhibition of Akt. Cell Cycle. 2013; 12:145-156.
50. Solforosi L, Criado JR, McGavern DB, Wirz S, Sanchez-Alavez M, Sugama S, DeGiorgio LA, Volpe BT, Wiseman E, Abalos G, Masliah E, Gilden D, Oldstone MB, Conti B and Williamson RA. Cross-linking cellular prion protein triggers neuronal apoptosis in vivo. Science. 2004; 303:1514-1516.
51. Sonati T, Reimann RR, Falsig J, Baral PK, O'Connor T, Hornemann S, Yaganoglu S, Li B, Herrmann US, Wieland B, Swayampakula M, Rahman MH, Das D, Kav N, Riek R, Liberski PP, et al. The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein. Nature. 2013; 501:102-106.
52. Soeda A, Inagaki A, Oka N, Ikegame Y, Aoki H, Yoshimura S, Nakashima S, Kunisada T and Iwama T. Epidermal growth factor plays a crucial role in mitogenic regulation of human brain tumor stem cells. The Journal of biological chemistry. 2008; 283:10958-10966.
53. Rota LM, Lazzarino DA, Ziegler AN, LeRoith D and Wood TL. Determining mammosphere-forming potential: application of the limiting dilution analysis. Journal of mammary gland biology and neoplasia. 2012; 17:119-123.
54. Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R and Young RA. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005; 122:947-956.
55. Zhang S and Cui W. Sox2, a key factor in the regulation of pluripotency and neural differentiation. World J Stem Cells. 2014; 6:305-311.
56. Gangemi R, Paleari L, Orengo AM, Cesario A, Chessa L, Ferrini S and Russo P. Cancer stem cells: a new paradigm for understanding tumor growth and progression and drug resistance. Current medicinal chemistry. 2009; 16:1688-1703.
57. Saunders A, Faiola F and Wang J. Concise review: pursuing self-renewal and pluripotency with the stem cell factor Nanog. Stem Cells. 2013; 31:1227-1236.
58. Sun AX, Liu CJ, Sun ZQ and Wei Z. NANOG: a promising target for digestive malignant tumors. World journal of gastroenterology. 2014; 20:13071-13078.
59. Bao S, Wu Q, Sathornsumetee S, Hao Y, Li Z, Hjelmeland AB, Shi Q, McLendon RE, Bigner DD and Rich JN. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer research. 2006; 66:7843-7848.
60. Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B, Oh EY, Gaber MW, Finklestein D, Allen M, Frank A, Bayazitov IT, Zakharenko SS, Gajjar A, Davidoff A and Gilbertson RJ. A perivascular niche for brain tumor stem cells. Cancer cell. 2007; 11:69-82.
61. Gilbertson RJ and Rich JN. Making a tumour's bed: glioblastoma stem cells and the vascular niche. Nat Rev Cancer. 2007; 7:733-736.
62. Lathia JD, Gallagher J, Heddleston JM, Wang J, Eyler CE, Macswords J, Wu Q, Vasanji A, McLendon RE, Hjelmeland AB and Rich JN. Integrin alpha 6 regulates glioblastoma stem cells. Cell stem cell. 2010; 6:421-432.
63. Aguzzi A and Polymenidou M. Mammalian prion biology: one century of evolving concepts. Cell. 2004; 116:313-327.
64. Miranda A, Ramos-Ibeas P, Pericuesta E, Ramirez MA and Gutierrez-Adan A. The role of prion protein in stem cell regulation. Reproduction. 2013; 146:R91-99.
65. Lopes MH and Santos TG. Prion potency in stem cells biology. Prion. 2012; 6:142-146.
66. Zhou L, Shang Y, Liu C, Li J, Hu H, Liang C, Han Y, Zhang W, Liang J and Wu K. Overexpression of PrPc, combined with MGr1-Ag/37LRP, is predictive of poor prognosis in gastric cancer. International journal of cancer. 2014; 135:2329-2337.
67. Cheng Y, Tao L, Xu J, Li Q, Yu J, Jin Y, Chen Q, Xu Z, Zou Q and Liu X. CD44/cellular prion protein interact in multidrug resistant breast cancer cells and correlate with responses to neoadjuvant chemotherapy in breast cancer patients. Molecular carcinogenesis. 2014; 53:686-697.
68. Barbieri G, Palumbo S, Gabrusiewicz K, Azzalin A, Marchesi N, Spedito A, Biggiogera M, Sbalchiero E, Mazzini G, Miracco C, Pirtoli L, Kaminska B and Comincini S. Silencing of cellular prion protein (PrPC) expression by DNA-antisense oligonucleotides induces autophagy-dependent cell death in glioma cells. Autophagy. 2011; 7:840-853.
69. Seymour T, Nowak A and Kakulas F. Targeting Aggressive Cancer Stem Cells in Glioblastoma. Frontiers in oncology. 2015; 5:159.
70. Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM, Pastorino S, Purow BW, Christopher N, Zhang W, Park JK and Fine HA. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serumcultured cell lines. Cancer cell. 2006; 9:391-403.
71. Gritti M, Wurth R, Angelini M, Barbieri F, Peretti M, Pizzi E, Pattarozzi A, Carra E, Sirito R, Daga A, Curmi PM, Mazzanti M and Florio T. Metformin repositioning as antitumoral agent: selective antiproliferative effects in human glioblastoma stem cells, via inhibition of CLIC1-mediated ion current. Oncotarget. 2014; 5:11252-11268. doi: 10.18632/oncotarget.2617.
72. Wilhelmsson U, Eliasson C, Bjerkvig R and Pekny M. Loss of GFAP expression in high-grade astrocytomas does not contribute to tumor development or progression. Oncogene. 2003; 22:3407-3411.
73. Prodromidou K, Papastefanaki F, Sklaviadis T and Matsas R. Functional cross-talk between the cellular prion protein and the neural cell adhesion molecule is critical for neuronal differentiation of neural stem/precursor cells. Stem Cells. 2014; 32:1674-1687.
74. Mohanty ST, Cairney CJ, Chantry AD, Madan S, Fernandes JA, Howe SJ, Moore HD, Thompson MJ, Chen B, Thrasher A, Keith WN and Bellantuono I. A small molecule modulator of prion protein increases human mesenchymal stem cell lifespan, ex vivo expansion, and engraftment to bone marrow in NOD/SCID mice. Stem Cells. 2012; 30:1134-1143.
75. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A and Weinberg RA. An embryonic stem celllike gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 2008; 40:499-507.
76. Jun HJ, Bronson RT and Charest A. Inhibition of EGFR induces a c-MET-driven stem cell population in glioblastoma. Stem Cells. 2014; 32:338-348.
77. Gangemi RM, Griffero F, Marubbi D, Perera M, Capra MC, Malatesta P, Ravetti GL, Zona GL, Daga A and Corte G. SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity. Stem Cells. 2009; 27:40-48.
78. Kim RK, Yoon CH, Hyun KH, Lee H, An S, Park MJ, Kim MJ and Lee SJ. Role of lymphocyte-specific protein tyrosine kinase (LCK) in the expansion of glioma-initiating cells by fractionated radiation. Biochemical and biophysical research communications. 2010; 402:631-636.
79. Sempou E, Biasini E, Pinzon-Olejua A, Harris DA and Malaga-Trillo E. Activation of zebrafish Src family kinases by the prion protein is an amyloid-beta-sensitive signal that prevents the endocytosis and degradation of E-cadherin/beta-catenin complexes in vivo. Molecular neurodegeneration. 2016; 11:18.
80. Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG and Parada LF. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. 2012; 488:522-526.
81. Kolosa K, Motaln H, Herold-Mende C, Korsic M and Lah TT. Paracrine effects of mesenchymal stem cells induce senescence and differentiation of glioblastoma stem-like cells. Cell Transplant. 2015; 24:631-644.
82. Kang TW, Choi SW, Yang SR, Shin TH, Kim HS, Yu KR, Hong IS, Ro S, Cho JM and Kang KS. Growth arrest and forced differentiation of human primary glioblastoma multiforme by a novel small molecule. Sci Rep. 2014; 4:5546.
83. Tchoghandjian A, Jennewein C, Eckhardt I, Momma S, Figarella-Branger D and Fulda S. Smac mimetic promotes glioblastoma cancer stem-like cell differentiation by activating NF-kappaB. Cell Death Differ. 2014; 21:735-747.
84. Adam SA, Schnell O, Poschl J, Eigenbrod S, Kretzschmar HA, Tonn JC and Schuller U. ALDH1A1 is a marker of astrocytic differentiation during brain development and correlates with better survival in glioblastoma patients. Brain Pathol. 2012; 22:788-797.
85. Dery MA, Jodoin J, Ursini-Siegel J, Aleynikova O, Ferrario C, Hassan S, Basik M and LeBlanc AC. Endoplasmic reticulum stress induces PRNP prion protein gene expression in breast cancer. Breast cancer research. 2013; 15:R22.
86. Barbieri F, Pattarozzi A, Gatti M, Porcile C, Bajetto A, Ferrari A, Culler MD and Florio T. Somatostatin receptors 1, 2, and 5 cooperate in the somatostatin inhibition of C6 glioma cell proliferation in vitro via a phosphotyrosine phosphatase-eta-dependent inhibition of extracellularly regulated kinase-1/2. Endocrinology. 2008; 149:4736-4746.
87. Corsaro A, Thellung S, Chiovitti K, Villa V, Simi A, Raggi F, Paludi D, Russo C, Aceto A and Florio T. Dual modulation of ERK1/2 and p38 MAP kinase activities induced by minocycline reverses the neurotoxic effects of the prion protein fragment 90-231. Neurotox Res. 2009; 15:138-154.
88. Villa V, Thellung S, Corsaro A, Novelli F, Tasso B, Colucci-D'Amato L, Gatta E, Tonelli M and Florio T. Celecoxib Inhibits Prion Protein 90-231-Mediated Pro-inflammatory Responses in Microglial Cells. Molecular neurobiology. 2016; 53:57-72.
89. Carra E, Barbieri F, Marubbi D, Pattarozzi A, Favoni RE, Florio T and Daga A. Sorafenib selectively depletes human glioblastoma tumor-initiating cells from primary cultures. Cell Cycle. 2013; 12:491-500.
90. Banelli B, Carra E, Barbieri F, Wurth R, Parodi F, Pattarozzi A, Carosio R, Forlani A, Allemanni G, Marubbi D, Florio T, Daga A and Romani M. The histone demethylase KDM5A is a key factor for the resistance to temozolomide in glioblastoma. Cell Cycle. 2015; 14:3418-3429.