Glioblastoma pp 167-183 | Cite as

Divide and Invade: The Dynamic Cytoskeleton of Glioblastoma Cells

  • Jim Cardelli
  • Omar Skalli


This chapter first provides an overview of emerging concepts on how the cytoskeleton participates in the malignant behavior of cancer cells with an emphasis on glioblastomas (GBMs). Then, it reviews cytoskeletal proteins specific to GBMs versus normal brain cells, and what is known about the role of these proteins in motility and invasion. The potential of cytoskeletal proteins as therapeutic targets is also considered. The studies reviewed in this chapter have established that the cytoskeletal protein composition of GBMs differs extensively from that of normal astrocytes and/or lower-grade astrocytomas. Such studies can provide the basis to develop strategies to target cytoskeletal proteins other than tubulin to lead GBM cells to their demise.


Cytoskeletal proteins Glioblastomas Motility and invasion Therapeutic targets 


  1. Bellail AC, Hunter SB, Brat DJ, Tan C, Van Meir EG (2004) Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasion. Int J Biochem Cell Biol 36:1046–1069Google Scholar
  2. Bellin RM, Huiatt TW, Critchley DR, Robson RM (2001) Synemin may function to directly link muscle cell intermediate filaments to both myofibrillar Z-lines and costameres. J Biol Chem 276:32330–32337PubMedCrossRefGoogle Scholar
  3. Bellin RM, Sernett SW, Becker B, Ip W, Huiatt TW, Robson RM (1999) Molecular characteristics and interactions of the intermediate filament protein synemin. Interactions with alpha-actinin may anchor synemin-containing heterofilaments. J Biol Chem 274:29493–29499PubMedCrossRefGoogle Scholar
  4. Blechingberg J, Holm IE, Nielsen KB, Jensen TH, Jørgensen AL, Nielsen AL (2007) Identification and characterization of gfapκ, a novel glial fibrillary acidic protein isoform. Glia 55:497–507PubMedCrossRefGoogle Scholar
  5. Blümcke I, Becker AJ, Normann S, Hans V, Riederer BM, Krajewski S, Wiestler OD, Reifenberger G (2001) Distinct expression pattern of microtubule-associated protein-2 in human oligodendrogliomas and glial precursor cells. J Neuropathol Exp Neurol 60:984–993PubMedGoogle Scholar
  6. Bos JL, Rehmann H, Wittinghofer A (2007) GEFs and GAPs: Critical elements in the control of small G proteins. Cell 129:865–877PubMedCrossRefGoogle Scholar
  7. Bourguignon LY, Singleton PA, Diedrich F, Stern R, Gilad E (2004) CD44 interaction with Na+-H+ exchanger (NHE1) creates acidic microenvironments leading to hyaluronidase-2 and cathepsin B activation and breast tumor cell invasion. J Biol Chem 279:26991–27007PubMedCrossRefGoogle Scholar
  8. Bravo-Cordero JJ, Marrero-Diaz R, Megías D, Genís L, García-Grande A, García MA, Arroyo AG, Montoya MC (2007) MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway. EMBO J 26:1499–1510PubMedCrossRefGoogle Scholar
  9. Carlier MF, Pantaloni D (2007) Control of actin assembly dynamics in cell motility. J Biol Chem 282:23005–23009PubMedCrossRefGoogle Scholar
  10. Caswell PT, Norman JC (2006) Integrin trafficking and the control of cell migration. Traffic 7:14–21PubMedCrossRefGoogle Scholar
  11. Caviston JP, Holzbaur EL (2006) Microtubule motors at the intersection of trafficking and transport. Trends Cell Biol 16:530–537PubMedCrossRefGoogle Scholar
  12. Chang L, Goldman RD (2004) Intermediate filaments mediate cytoskeletal crosstalk. Nat Rev Mol Cell Biol 5:601–613PubMedCrossRefGoogle Scholar
  13. Chou YH, Khuon S, Herrmann H, Goldman RD (2003) Nestin promotes the phosphorylation-dependent disassembly of vimentin intermediate filaments during mitosis. Mol Biol Cell 14:1468–1478PubMedCrossRefGoogle Scholar
  14. Chumbalkar VC, Subhashini C, Dhople VM, Sundaram CS, Jagannadham MV, Kumar KN, Srinivas PN, Mythili R, Rao MK, Kulkarni MJ, Hegde S, Hegde AS, Samual C, Santosh V, Singh L, Sirdeshmukh R (2005) Differential protein expression in human gliomas and molecular insights. Proteomics 5:1167–1177PubMedCrossRefGoogle Scholar
  15. Dahlstrand J, Collins PV, Lendhal U (1992) Expression of the class VI intermediate filament nestin in human central nervous tumors. Cancer Res 52:5334–5341Google Scholar
  16. Daou MC, Smith TW, Litofsky NS, Hsieh CC, Ross AH (2005) Doublecortin is preferentially expressed in invasive human brain tumors. Acta Neuropathol 110:472–480PubMedCrossRefGoogle Scholar
  17. Del Bigio MR, Deck JH (1993) Rosenthal fibers producing a granular cell appearance in a glioblastoma. Acta Neuropathol 86:100–104PubMedCrossRefGoogle Scholar
  18. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703–716PubMedCrossRefGoogle Scholar
  19. Edelman G, Yahara I (1976) Temperature-sensitive changes in surface-modulating assemblies of fibroblasts transformed by mutants of Rous sarcoma virus. Proc Natl Acad Sci USA 73:2047–2051PubMedCrossRefGoogle Scholar
  20. Eliasson C, Sahlgren C, Berthold CH, Stakeberg J, Celis JE, Betsholtz C, Eriksson JE, Pekny M (1999) Intermediate filament protein partnership in astrocytes. J Biol Chem 274:23996–24006PubMedCrossRefGoogle Scholar
  21. Elobeid A, Bongcam-Rudloff E, Westermark B, Nistér M (2000) Effects of inducible glial fibrillary acidic protein on glioma cell motility and proliferation. J Neurosci Res 60:245–256PubMedCrossRefGoogle Scholar
  22. Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 25:1439–1451PubMedCrossRefGoogle Scholar
  23. Eriksson JE, Brautigan DL, Vallee R, Olmsted J, Fujiki H, Goldman RD (1992) Cytoskeletal integrity in interphase cells requires protein phosphatase activity. Proc Natl Acad Sci USA 89:11093–11097PubMedCrossRefGoogle Scholar
  24. Even-Ram S, Yamada KM (2005) Cell migration in 3D matrix. Curr Opin Cell Biol 17:524–532PubMedCrossRefGoogle Scholar
  25. Even-Ram S, Doyle AD, Conti MA, Matsumoto K, Adelstein RS, Yamada KM (2007) Myosin IIA regulates cell motility and actomyosin–microtubule crosstalk. Nat Cell Biol 9:299–309PubMedCrossRefGoogle Scholar
  26. Failly M, Korur S, Egler V, Boulay J-L, Lino MM, Imber R, Merlo A (2007) Combination of sublethal concentrations of epidermal growth factor receptor inhibitor and microtubule stabilizer induces apoptosis of glioblastoma cells. Mol Cancer Ther 6:773–781PubMedCrossRefGoogle Scholar
  27. Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhänel M, Spruß T, Bernhardt G, Graeff C, Färber L, Gschaidmeier H, Buschauer A, Fricker G (2002) Transport of paclitaxel (Taxol) across the blood-brainbarrier in vitro and in vivo J. Clin Invest 110:1309–1318Google Scholar
  28. Galea E, Dupouey P, Feinstein DL (1995) Glial fibrillary acidic protein mRNA isotypes: Expression in vitro and in vivo. J Neurosci Res 41:452–461PubMedCrossRefGoogle Scholar
  29. Geiger KD, Stoldt P, Schlote W, Derouiche A (2000) Ezrin immunoreactivity is associated with increasing malignancy of astrocytic tumors but is absent in oligodendrogliomas. Am J Pathol 157:1785–1793PubMedGoogle Scholar
  30. Gillespie GY, Soroceanu L, Manning TJ Jr, Gladson CL, Rosenfeld SS (1999) Glioma migration can be blocked by nontoxic inhibitors of myosin II. Canc Res 59:2076–2082Google Scholar
  31. Goldman RD, Khuon S, Chou YH, Opal P, Steinert PM (1996) The function of intermediate filaments in cell shape and cytoskeletal integrity. J Cell Biol 134:971–983PubMedCrossRefGoogle Scholar
  32. Goode BL, Eck MJ (2007) Mechanism and function of formins in the control of actin assembly. Annu Rev Biochem 76:593–627PubMedCrossRefGoogle Scholar
  33. Gunnersen JM, Spirkoska V, Smith PE, Danks RA, Tan SS (2000) Growth and migration markers of rat C6 glioma cells identified by serial analysis of gene expression. Glia 32:146–154PubMedCrossRefGoogle Scholar
  34. Hamilton SR, Fard SF, Paiwand FF, Tolg C, Veiseh M, Wang C, McCarthy JB, Bissell MJ, Koropatnick J, Turley EA (2007) The hyaluronan receptors CD44 and Rhamm (CD168) form complexes with ERK1, 2 that sustain high basal motility in breast cancer cells. J Biol Chem 282:16667–16680PubMedCrossRefGoogle Scholar
  35. Hatzfeld M, Weber K (1992) A synthetic peptide representing the consensus sequence motif at the carboxy-terminal end of the rod domain inhibits intermediate filament assembly and disassembles preformed filaments. J Cell Biol 116:157–166PubMedCrossRefGoogle Scholar
  36. Hayot C, Debeir O, Van Ham P, Van Damme M, Kiss R, Decaestecker C (2006) Characterization of the activities of actin-affecting drugs on tumor cell migration. Tox Appl Pharmacol 211:30–40CrossRefGoogle Scholar
  37. Herpers MJ, Ramaekers FCS, Aldeweireldt J, Moesker O, Sloof J (1986) Co-expression of glial fibrillary acidic protein and vimentin-type intermediate filaments in human astrocytomas. Acta Neuropathol 70:333–339PubMedCrossRefGoogle Scholar
  38. Hoelzinger DB, Mariani L, Weis J, Woyke T, Berens TJ, McDonough WS, Sloan A, Coons SW, Berens ME (2005) Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia 7:7–16PubMedCrossRefGoogle Scholar
  39. Hooper S, Marshall JF, Sahai E (2006) Tumor cell migration in three dimensions. Meth Enzymol 406:625–643PubMedCrossRefGoogle Scholar
  40. Horwitz SB (1994) Taxol (paclitaxel): Mechanisms of action. Ann Oncol 5(Suppl 6):S3–S6PubMedGoogle Scholar
  41. Hwang TL, Borit A (1982) Rosenthal fibers in glioblastoma multiforme. Acta Neuropathol 57:230–232PubMedCrossRefGoogle Scholar
  42. Hyun Hwang J, Smith CA, Salhia B, Rutka JT (2008) The role of fascin in the migration and invasiveness of malignant glioma cells. Neoplasia 10:149–159CrossRefGoogle Scholar
  43. Jing R, Pizzolato G, Robson RM, Gabbiani G, Skalli O (2005) Intermediate filament protein synemin is present in human reactive and malignant astrocytes and associates with ruffled membranes in astrocytoma cells. Glia 50:107–120PubMedCrossRefGoogle Scholar
  44. Jing R, Wilhelmsson U, Goodwill W, Li L, Pan Y, Pekny M, Skalli O (2007) Synemin is expressed in reactive astrocytes in neurotrauma and interacts differentially with vimentin and GFAP intermediate filament networks. J Cell Sci 120:1267–1277PubMedCrossRefGoogle Scholar
  45. Jordan MA, Kamath K (2007) How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets 7:730–742PubMedCrossRefGoogle Scholar
  46. Jordan MA, Wilson L (1998) Microtubules and actin filaments: Dynamic targets for cancer chemotherapy. Curr Opin Cell Biol 10:193–130Google Scholar
  47. Joy AM, Beaudry CE, Tran NL, Ponce FA, Holz DR, Demuth T, Berens ME (2003) Migrating glioma cells activate the PI3-K pathway and display decreased susceptibility to apoptosis. J Cell Sci 116:4409–4417PubMedCrossRefGoogle Scholar
  48. Kapoor TM, Mayer TU, Coughlin ML, Mitchison TJ (2000) Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J Cell Biol 150:975–988PubMedCrossRefGoogle Scholar
  49. Katsetos CD, Dráberová E, Smejkalová B, Reddy G, Bertrand L, de Chadarévian JP, Legido A, Nissanov J, Baas PW, Dráber P (2007) Class III beta-tubulin and gamma-tubulin are co-expressed and form complexes in human glioblastoma cells. Neurochem Res 32:1387–1398PubMedCrossRefGoogle Scholar
  50. Katsetos CD, Legido A, Perentes E, Mörk SJ (2003) Class III beta-tubulin isotype: A key cytoskeletal protein at the crossroads of developmental neurobiology and tumor neuropathology. J Child Neurol 18:851–866PubMedCrossRefGoogle Scholar
  51. Katsetos CD, Reddy G, Dráberová E, Smejkalová B, Del Valle L, Ashraf Q, Tadevosyan A, Yelin K, Maraziotis T, Mishra OP, Mörk S, Legido A, Nissanov J, Baas PW, de Chadarévian JP, Dráber P (2006) Altered cellular distribution and subcellular sorting of gamma-tubulin in diffuse astrocytic gliomas and human glioblastoma cell lines. J Neuropathol Exp Neurol 65:465–477PubMedCrossRefGoogle Scholar
  52. Kavallaris M, Kuo DY, Burkhart CA, Regl DL, Norris MD, Haber M, Horwitz SB (1997) Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J Clin Invest 100:1282–1293PubMedCrossRefGoogle Scholar
  53. Kawataki T, Yamane T, Naganuma H, Rousselle P, Andurén I, Tryggvason K, Patarroyo M (2007) Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: Evidence for a role of alpha5-laminin(s) and alpha3beta1 integrin. Exp Cell Res 313:3819–3831PubMedCrossRefGoogle Scholar
  54. Kelly P, Casey PJ, Meigs TE (2007) Biologic functions of the G12 subfamily of heterotrimeric g proteins: Growth, migration, and metastasis. Biochemistry 46:6677–6687PubMedCrossRefGoogle Scholar
  55. Kleeberger W, Bova GS, Nielsen ME, Herawi M, Chuang AY, Epstein JI, Berman DM (2007) Roles for the stem cell associated intermediate filament Nestin in prostate cancer migration and metastasis. Cancer Res 67:9199–9206PubMedCrossRefGoogle Scholar
  56. Klotzsche O, Etzrodt D, Hohenberg H, Bohn W, Deppert W (1998) Cytoplasmic retention of mutant tsp53 is dependent on an intermediate filament protein (vimentin) scaffold. Oncogene 16:3423–3434PubMedCrossRefGoogle Scholar
  57. Koller E, Propp S, Zhang H, Zhao C, Xiao X, Chang M, Hirsch SA, Shepard PJ, Koo S, Murphy C, Glazer RI, Dean NM (2006) Use of a chemically modified antisense oligonucleotide library to identify and validate Eg5 (kinesin-like 1) as a target for antineoplastic drug development. Cancer Res 66:2059–2066PubMedCrossRefGoogle Scholar
  58. Liberski PP (1998) The ultrastructure of glial tumors of astrocytic lineage: A review. Folia Neuropathol 36:161–177PubMedGoogle Scholar
  59. Ljubimova JY, Khazenzon NM, Chen Z, Neyman YI, Turner L, Riedinger MS, Black KL (2001a) Gene expression abnormalities in human glial tumors identified by gene array. Int J Oncol 18:287–295PubMedGoogle Scholar
  60. Ljubimova JY, Lakhter AJ, Loksh A, Yong WH, Riedinger MS, Miner JH, Sorokin LM, Ljubimov AV, Black KL (2001b) Overexpression of a4 chain-containing laminins in human glial tumors identified by gene microarray analysis. Cancer Res 61:5601–5610PubMedGoogle Scholar
  61. Marcus AI, Peters U, Thomas SL, Garrett S, Zelnak A, Kapoor TM, Giannakakou P (2005) Mitotic kinesin inhibitors induce mitotic arrest and cell death in Taxol-resistant and -sensitive cancer cells. J Biol Chem 280:11569–11577PubMedCrossRefGoogle Scholar
  62. Mariani L, Beaudry C, McDonough WS, Hoelzinger DB, Demuth TM, Ross KR, Berens T, Coons SW, Watts G, Trent JM, Wei JS, Giese A, Berens ME (2001) Glioma cell motility is associated with reduced transcription of proapoptotic and proliferation genes: A cDNA microarray analysis. J Neuro Oncol 53:161–176CrossRefGoogle Scholar
  63. Mayer TU, Kapoor TM, Haggarty SJ, King RW, Schreiber SL, Mitchison TJ (1999) Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 286:913–914CrossRefGoogle Scholar
  64. McLean LA, Roscoe J, Jorgensen NK, Gorin FA, Cala PM (2000) Malignant gliomas display altered pH regulation by NHE1 compared with nontransformed astrocytes. Am J Physiol Cell Physiol 278:C676–C688PubMedGoogle Scholar
  65. Mizuno Y, Thompson TG, Guyon JR, Lidov HG, Brosius M, Imamura M, Ozawa E, Watkins SC, Kunkel LM (2001) Desmuslin, an intermediate filament protein that interacts with alpha-dystrobrevin and desmin. Proc Natl Acad Sci USA 98:6156–6161PubMedCrossRefGoogle Scholar
  66. Muller C, Gross D, Sarli V, Gartner M, Giannis A, Bernhardt G, Buschauer A (2007) Inhibitors of kinesin Eg5: Antiproliferative activity of monastrol analogues against human glioblastoma cells. Cancer Chemother Pharmacol 59:157–164PubMedCrossRefGoogle Scholar
  67. Murphy KG, Hatton JD, U HS (1998) Role of glial fibrillary acidic protein expression in the biology of human glioblastoma U-373MG cells. J Neurosurg 89:997–1006Google Scholar
  68. Ngo TT, Peng T, Liang XJ, Akeju O, Pastorino S, Zhang W, Kotliarov Y, Zenklusen JC, Fine HA, Maric D, Wen PY, De Girolami U, Black PM, Wu WW, Shen RF, Jeffries NO, Kang DW, Park JK (2007) The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas. J Natl Cancer Inst 99:639–652PubMedCrossRefGoogle Scholar
  69. Nielsen AL, Jørgensen AL (2004) Self-assembly of the cytoskeletal glial fibrillary acidic protein is inhibited by an isoform-specific C terminus. J Biol Chem 279:41537–41545PubMedCrossRefGoogle Scholar
  70. Nielsen AL, Holm IE, Johansen M, Bonven B, Jørgensen P, Jørgensen AL (2002) A new splice variant of glial fibrillary acidic protein, GFAPε, interacts with the presenilin proteins J. Biol Chem 277:29983–29991CrossRefGoogle Scholar
  71. Nutt CL, Mani DR, Betensky RA, Tamayo P, Cairncross JG, Ladd C, Pohl U, Hartmann C, McLaughlin ME, Batchelor TT, Black PM, von Deimling A, Pomeroy SL, Golub TR, Louis DN (2003) Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res 63:1602–1607PubMedGoogle Scholar
  72. Omary MB, Coulombe PA, McLean WH (2004) Intermediate filament proteins and their associated diseases. N Engl J Med 351:2087–2100PubMedCrossRefGoogle Scholar
  73. Orr GA, Verdier-Pinard P, McDaid H, Horwitz SB (2003) Mechanisms of Taxol resistance related to microtubules. Oncogene 22:7280–7295PubMedCrossRefGoogle Scholar
  74. Pan Y, Jing R, Pitre A, Williams BJ, Skalli O (2008) Intermediate filament protein synemin contributes to the migratory properties of astrocytoma cells by influencing the dynamics of the actin cytoskeleton. FASEB J 22:3196–3206Google Scholar
  75. Pekny M, Pekna M (2004) Astrocyte intermediate filaments in CNS pathologies and regeneration. J Pathol 204:428–437PubMedCrossRefGoogle Scholar
  76. Pellinen T, Ivaska J (2006) Integrin traffic. J Cell Sci 119:3723–3731PubMedCrossRefGoogle Scholar
  77. Pellinen T, Arjonen A, Vuoriluoto K, Kallio K, Fransen JA, Ivaska J (2006) Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of beta1-integrins. J Cell Biol 173:767–780PubMedCrossRefGoogle Scholar
  78. Peraud A, Mondal S, Hawkins C, Mastronardi M, Bailey K, Rutka JT (2003) Expression of fascin, an actin-bundling protein, in astrocytomas of varying grades. Brain Tumor Pathol 20:53–58PubMedCrossRefGoogle Scholar
  79. Pollack R, Osborn M, Weber K (1975) Patterns of organization of actin and myosin in normal and transformed cultured cells. Proc Natl Acad Sci USA 72:994–998PubMedCrossRefGoogle Scholar
  80. Powelka AM, Sun J, Li J, Gao M, Shaw LM, Sonnenberg A, Hsu VW (2004) Stimulation-dependent recycling of integrin beta1 regulated by ARF6 and Rab11. Traffic 5:20–36PubMedCrossRefGoogle Scholar
  81. Ramsay AG, Marshall JF, Hart IR (2007) Integrin trafficking and its role in cancer metastasis. Cancer Metastasis Rev 26:567–578PubMedCrossRefGoogle Scholar
  82. Rao JY, Li N (2004) Microfilament actin remodeling as a potential target for cancer drug development. Curr Canc Drug Targets 4:345–354CrossRefGoogle Scholar
  83. Rempel SA, Rosenblum ML, Mikkelsen T, Yan PS, Ellis KD, Golembieski WA, Sameni M, Rozhin J, Ziegler G, Sloane BF (1994) Cathepsin B expression and localization in glioma progression and invasion. Cancer Res 54:6027–6031PubMedGoogle Scholar
  84. Rich JN, Hans C, Jones B, Iversen ES, McLendon RE, Rasheed BK, Dobra A, Dressman HK, Bigner DD, Nevins JR, West M (2005) Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res 65:4051–4058PubMedCrossRefGoogle Scholar
  85. Rickman DS, Bobek MP, Misek DE, Kuick R, Blaivas M, Kurnit DM, Taylor J, Hanash SM (2001) Distinctive molecular profiles of high-grade and low-grade gliomas based on oligonucleotide microarray analysis. Cancer Res 61:6885–6891PubMedGoogle Scholar
  86. Rutka JT, Smith SL (1993) Transfection of human astrocytoma cells with glial fibrillary acidic protein complementary DNA: Analysis of expression, proliferation, and tumorigenicity. Cancer Res 53:3624–3631PubMedGoogle Scholar
  87. Rutka JT, Hubbard SL, Fukuyama K, Matsuzawa K, Dirks PB, Becker LE (1994) Effects of antisense glial fibrillary acidic protein complementary DNA on the growth, invasion, and adhesion of human astrocytoma cells. Cancer Res 54:3267–3272PubMedGoogle Scholar
  88. Rutka JT, Murakami M, Dirks PB, Hubbard SL, Becker LE, Fukuyama K, Jung S, Tsugu A, Matsuzawa K (1997) Role of glial filaments in cells and tumors of glial origin: A review. J Neurosurg 87:420–430PubMedCrossRefGoogle Scholar
  89. Sahlgren CM, Pallari HM, He T, Chou YH, Goldman RD, Eriksson JE (2006) A nestin scaffold links Cdk5/p35 signaling to oxidant-induced cell death. EMBO J 25:4808–4819PubMedCrossRefGoogle Scholar
  90. Sallinen SL, Sallinen PK, Haapasalo HK, Helin HJ, Helén PT, Schraml P, Kallioniemi OP, Kononen J (2000) Identification of differentially expressed genes in human gliomas by DNA microarray and tissue chip techniques. Cancer Res 60:6617–6622PubMedGoogle Scholar
  91. Santra M, Zhang X, Santra S, Jiang F, Chopp M (2006a) Ectopic doublecortin gene expression suppresses the malignant phenotype in glioblastoma cells. Cancer Res 66:11726–11735PubMedCrossRefGoogle Scholar
  92. Santra M, Liu XS, Santra S, Zhang J, Zhang RL, Zhang ZG, Chopp M (2006b) Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation. Neuroscience 142:739–752PubMedCrossRefGoogle Scholar
  93. Schiffer D, Giordana MT, Mauro A, Migheli A, Germano I, Giaccone G (1986) Immunohistochemical demonstration of vimentin in human cerebral tumors. Acta Neuropathol 70:209–216PubMedCrossRefGoogle Scholar
  94. Schmitt-Graeff A, Jing R, Desmoulieres A, Skalli O (2006) Synemin expression is widespread in liver fibrosis and is induced in proliferating and malignant biliary epithelial duct cells. Hum Pathol 37:1200–1210PubMedCrossRefGoogle Scholar
  95. Shih AH, Holland EC (2006) Notch signaling enhances nestin expression in gliomas. Neoplasia 8:1072–1082PubMedCrossRefGoogle Scholar
  96. Sivaparvathi M, Sawaya R, Wang SW, Rayford A, Yamamoto M, Liotta LA, Nicolson GL, Rao JS (1995) Overexpression and localization of cathepsin B during the progression of human gliomas. Clin Exp Metastasis 13:49–56PubMedCrossRefGoogle Scholar
  97. Snider JL, Allison C, Bellaire BH, Ferrero RL, Cardelli JA (2008) The beta 1 integrin activates jnk independent of caga, and jnk activation is required for helicobacter pylori caga+ induced motility of gastric cancer cells. J Biol Chem 283:13952–13963Google Scholar
  98. Soon L, Braet F, Condeelis J (2007) Moving in the right direction-nanoimaging in cancer cell motility and metastasis. Microsc Res Tech 70:252–257PubMedCrossRefGoogle Scholar
  99. Steffan JJ, Snider JL, Skalli O, Welbourne T, Cardelli JA (2009) Na/H exchangers and RhoA regulate acidic extracellular pH-induced lysosome trafficking in prostate cancer cells. Traffic 10:737–753Google Scholar
  100. Steinert PM, Chou YH, Prahlad V, Parry DA, Marekov LN, Wu KC, Jang SI, Goldman RD (1999) A high molecular weight intermediate filament-associated protein in BHK-21 cells is nestin, a type VI intermediate filament protein. Limited co-assembly in vitro to form heteropolymers with type III vimentin and type IV alpha-internexin. J Biol Chem 274:9881–9890PubMedCrossRefGoogle Scholar
  101. Stock C, Cardone RA, Busco G, Krähling H, Schwab A, Reshkin SJ (2008) Protons extruded by NHE1: Digestive or glue? Eur J Cell Biol 87:591–599Google Scholar
  102. Stournaras C, Stiakaki E, Koukouritaki SB, Theodoropoulos PA, Kahnanti M, Fostinis Y, Gravanis A (1996) Altered actin polymerization dynamics in various malignant cell types: Evidence for differential sensitivity to cytochalasin B. Biochem Pharmacol 52:1339–1346PubMedCrossRefGoogle Scholar
  103. Sultana S, Sernett SW, Bellin RM, Robson RM, Skalli O (2000) The intermediate filament protein synemin is transiently expressed in a subpopulation of astrocytes during development. Glia 30:143–153PubMedCrossRefGoogle Scholar
  104. Sultana S, Zhou R, Sadagopan MS, Skalli O (1998) Effects of growth factors and basement membrane proteins on the phenotype of U-373 MG glioblastoma cells as determined by the expression of intermediate filament proteins. Am J Pathol 153:1157–1168PubMedGoogle Scholar
  105. Suzuki SO, Kitai R, Llena J, Lee SC, Goldman JE, Shafit-Zagardo B (2002) MAP-2e, a novel MAP-2 isoform, is expressed in gliomas and delineates tumor architecture and patterns of infiltration. J Neuropathol Exp Neurol 61:403–412PubMedGoogle Scholar
  106. Suzuki SO, McKenney RJ, Mawatari SY, Mizuguchi M, Mikami A, Iwaki T, Goldman JE, Canoll P, Vallee RB (2007) Expression patterns of LIS1, dynein and their interaction partners dynactin, NudE, NudEL and NudC in human gliomas suggest roles in invasion and proliferation. Acta Neuropathol 113:591–599PubMedCrossRefGoogle Scholar
  107. Tolg C, Hamilton SR, Nakrieko KA, Kooshesh F, Walton P, McCarthy JB, Bissell MJ, Turley EA (2006) Rhamm–/– fibroblasts are defective in CD44-mediated ERK1, 2 motogenic signaling, leading to defective skin wound repair. J Cell Biol 175:1017–1028PubMedCrossRefGoogle Scholar
  108. Tynninen O, Carpén O, Jääskeläinen J, Paavonen T, Paetau A (2004) Ezrin expression in tissue microarray of primary and recurrent gliomas. Neuropathol Appl Neurobiol 30:472–477PubMedCrossRefGoogle Scholar
  109. Vale RD (2003) The molecular motor toolbox for intracellular transport. Cell 112:467–480PubMedCrossRefGoogle Scholar
  110. Wade RH (2007) Microtubules: An overview. Methods Mol Med 137:1–16PubMedCrossRefGoogle Scholar
  111. Wakamatsu Y, Nakamura N, Lee JA, Cole GJ, Osumi N (2007) Transitin, a nestin-like intermediate filament protein, mediates cortical localization and the lateral transport of Numb in mitotic avian neuroepithelial cells. Development 134:2425–2433PubMedCrossRefGoogle Scholar
  112. Wang W, Eddy R, Condeelis J (2007) The cofilin pathway in breast cancer invasion and metastasis. Nat Rev Cancer 7:429–440PubMedCrossRefGoogle Scholar
  113. Watanabe T, Noritake J, Kaibuchi K (2005) Regulation of microtubules in cell migration. Trends Cell Biol 15:76–83PubMedCrossRefGoogle Scholar
  114. Wharton SB, Chan KK, Whittle IR (2002) Microtubule-associated protein 2 (MAP-2) is expressed in low and high grade diffuse astrocytomas. J Clin Neurosci 9:165–169PubMedCrossRefGoogle Scholar
  115. Wick W, Grimmel C, Wild-Bode C, Platten M, Arpin M, Weller M (2001) Ezrin-dependent promotion of glioma cell clonogenicity, motility, and invasion mediated by BCL-2 and transforming growth factor-beta2. J Neurosci 21:3360–3368PubMedGoogle Scholar
  116. Wilhelmsson U, Eliasson C, Bjerkvig R, Pekny M (2003) Loss of GFAP expression in high-grade astrocytomas does not contribute to tumor development or progression Oncogene 22:3407–3411Google Scholar
  117. Yap CT, Simpson TI, Pratt T, Price DJ, Maciver SK (2005) The motility of glioblastoma tumour cells is modulated by intracellular cofilin expression in a concentration-dependent manner. Cell Motil Cytoskeleton 60:153–165PubMedCrossRefGoogle Scholar
  118. Yokota T, Kouno J, Adachi K, Takahashi H, Teramoto A, Matsumoto K, Sugisaki Y, Onda M, Tsunoda T (2006) Identification of histological markers for malignant glioma by genome-wide expression analysis: Dynein, alpha-PIX and sorcin. Acta Neuropathol 111:29–38PubMedCrossRefGoogle Scholar
  119. Yoon SO, Shin S, Mercurio AM (2005) Hypoxia stimulates carcinoma invasion by stabilizing microtubules and promoting the Rab11 trafficking of the alpha6beta4 integrin. Cancer Res 65:2761–2769PubMedCrossRefGoogle Scholar
  120. Yung WKA, Luna M, Borit A (1985) Vimentin and glial fibrillary acidic protein in human brain tumors. J Neuro-Oncol 3:35–38CrossRefGoogle Scholar
  121. Zhang ZY (2002) Protein tyrosine phosphatases: Structure and function, substrate specificity, and inhibitor development. Annu Rev Pharmacol Toxicol 42:209–234PubMedCrossRefGoogle Scholar
  122. Zhou R, Skalli O (2000) TGF-alpha differentially regulates GFAP, vimentin, and nestin gene expression in U-373 MG glioblastoma cells: Correlation with cell shape and motility. Exp Cell Res 254:269–278PubMedCrossRefGoogle Scholar
  123. Zhou R, Wu X, Skalli O (2002) The hyaluronan receptor RHAMM/IHABP in astrocytoma cells: Expression of a tumor-specific variant and association with microtubules. J Neurooncol 59:15–26PubMedCrossRefGoogle Scholar
  124. Zhu C, Zhao J, Bibikova M, Leverson JD, Bossy-Wetzel E, Fan JB, Abraham RT, Jiang W (2005) Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference. Mol Biol Cell 16:3187–3199PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York 2010

Authors and Affiliations

  1. 1.Department of Cellular Biology and Anatomy and Feist Weiller Cancer CenterLouisiana State University Health Sciences CenterShreveportUSA

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