Asymmetric cell division of stem and progenitor cells during homeostasis and cancer

Cellular and Molecular Life Sciences

Volumn 71, Issue 4, 2014, Pages 575-597

  Gómez López, Sandra ^a   Lerner, Robin G ^a   Petritsch, Claudia ^a,b,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Asymmetric cell division; Cancer stem cell; Glioma; Neural stem cell; Oligodendrocyte precursor cell; Polarity; Tumor propagating cell

Indexed keywords

ANIMAL; ASYMMETRIC CELL DIVISION; CYTOLOGY; HOMEOSTASIS; HUMAN; METABOLISM; NEOPLASM; NEURAL STEM CELL; PATHOLOGY; STEM CELL;

ANIMALS; ASYMMETRIC CELL DIVISION; HOMEOSTASIS; HUMANS; NEOPLASMS; NEURAL STEM CELLS; STEM CELLS;

EID: 84895195622     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-013-1386-1     Document Type: Review

References (235)

1. Morrison SJ, Kimble J (2006) Asymmetric and symmetric stem-cell divisions in development and cancer. Nature 441:1068-1074. doi: 10.1038/nature04956
2. Noctor SC, Martínez-Cerdeño V, Ivic L et al (2004) Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci 7:136-144. doi: 10.1038/nn1172
3. Sugiarto S, Persson AI, Munoz EG et al (2011) Asymmetry-defective oligodendrocyte progenitors are glioma precursors. Cancer Cell 20:328-340. doi: 10.1016/j.ccr.2011.08.011
4. Wu M, Kwon HY, Rattis F et al (2007) Imaging hematopoietic precursor division in real time. Cell Stem Cell 1:541-554. doi: 10.1016/j.stem.2007.08.009
5. Cicalese A, Bonizzi G, Pasi CE et al (2009) The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell 138:1083-1095. doi: 10.1016/j.cell.2009.06.048
6. Lathia JD, Hitomi M, Gallagher J et al (2011) Distribution of CD133 reveals glioma stem cells self-renew through symmetric and asymmetric cell divisions. Cell Death Dis 2:e200. doi: 10.1038/cddis.2011.80
7. Knoblich JA (2010) Asymmetric cell division: recent developments and their implications for tumour biology. Nat Rev Mol Cell Biol 11:849-860. doi: 10.1038/nrm3010
8. Bello BC, Izergina N, Caussinus E, Reichert H (2008) Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development. Neural Dev 3:5. doi: 10.1186/1749-8104-3-5
9. Boone JQ, Doe CQ (2008) Identification of Drosophila type II neuroblast lineages containing transit amplifying ganglion mother cells. Dev Neurobiol 68:1185-1195. doi: 10.1002/dneu.20648
10. Bowman SK, Rolland V, Betschinger J et al (2008) The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast lineages in Drosophila. Dev Cell 14:535-546. doi: 10.1016/j.devcel.2008.03.004
11. Schaefer M, Shevchenko A, Knoblich JA (2000) A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Curr Biol 10:353-362
12. Atwood SX, Chabu C, Penkert RR et al (2007) Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6 aPKC. J Cell Sci 120:3200-3206. doi: 10.1242/jcs.014902
13. Peterson FC, Penkert RR, Volkman BF, Prehoda KE (2004) Cdc42 regulates the Par-6 PDZ domain through an allosteric CRIB-PDZ transition. Mol Cell 13:665-676
14. Wodarz A, Ramrath A (2000) Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. J Cell Biol 150:1361-1374
15. Willard FS, Kimple RJ, Siderovski DP (2004) Return of the GDI: the GoLoco motif in cell Division. Annu Rev Biochem 73:925-951
16. Yu F, Wang H, Qian H et al (2005) Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions. Genes Dev 19:1341-1353. doi: 10.1101/gad.1295505.eration
17. Ogawa H, Ohta N, Moon W, Matsuzaki F (2009) Protein phosphatase 2A negatively regulates aPKC signaling by modulating phosphorylation of Par-6 in Drosophila neuroblast asymmetric divisions. J Cell Sci 122:3242-3249. doi: 10.1242/jcs.050955
18. Wirtz-Peitz F, Nishimura T, Knoblich JA (2008) Linking cell cycle to asymmetric division: Aurora-A phosphorylates the Par complex to regulate Numb localization. Cell 135:161-173. doi: 10.1016/j.cell.2008.07.049
19. Chabu C, Doe CQ (2009) Twins/PP2A regulates aPKC to control neuroblast cell polarity and self-renewal. Dev Biol 330:399-405. doi: 10.1016/j.ydbio.2009. 04.014
20. Wang C, Chang KC, Somers G et al (2009) Protein phosphatase 2A regulates self-renewal of Drosophila neural stem cells. Development 136:2287-2296. doi: 10.1242/dev.035758
21. Krahn MP, Egger-Adam D, Wodarz A (2009) PP2A antagonizes phosphorylation of Bazooka by PAR-1 to control apical-basal polarity in dividing embryonic neuroblasts. Dev Cell 16:901-908. doi: 10.1016/j.devcel.2009.04.011
22. Januschke J, Llamazares S, Reina J, Gonzalez C (2011) Drosophila neuroblasts retain the daughter centrosome. Nat Commun 2:243. doi: 10.1038/ncomms1245
23. Rebollo E, Sampaio P, Januschke J et al (2007) Functionally unequal centrosomes drive spindle orientation in asymmetrically dividing Drosophila neural stem cells. Dev Cell 12:467-474. doi: 10.1016/j.devcel.2007.01.021
24. Siller KH, Doe CQ (2009) Spindle orientation during asymmetric cell division. Nat Cell Biol 11:365-374. doi: 10.1038/ncb0409-365
25. Izumi Y, Ohta N, Hisata K et al (2006) Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization. Nat Cell Biol 8:586-593. doi: 10.1038/ncb1409
26. Siller KH, Cabernard C, Doe CQ (2006) The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts. Nat Biotechnol 8:594-600. doi: 10.1038/ncb1412
27. Bowman SK, Neumüller RA, Novatchkova M et al (2006) The Drosophila NuMA Homolog Mud regulates spindle orientation in asymmetric cell division. Dev Cell 10:731-742. doi: 10.1016/j.devcel.2006.05.005
28. Siegrist SE, Doe CQ (2005) Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts. Cell 123:1323-1335. doi: 10.1016/j.cell.2005.09.043
29. Siegrist SE, Doe CQ (2007) Microtubule-induced cortical cell polarity. Genes Dev 21:483-496. doi: 10.1101/gad.1511207
30. Wang H, Ouyang Y, Somers WG et al (2007) Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon. Nature 449:96-100. doi: 10.1038/nature06056
31. Wang H, Somers GW, Bashirullah A et al (2006) Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. Genes Dev 20:3453-3463. doi: 10.1101/gad.1487506
32. Lee C-Y, Andersen RO, Cabernard C et al (2006) Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes Dev 20:3464-3474. doi: 10.1101/gad.1489406
33. Kraut R, Chia W, Jan LY et al (1996) Role of inscuteable in orienting asymmetric cell divisions in Drosophila. Nature 383:50-55. doi: 10.1038/383050a0
34. Petritsch C, Tavosanis G, Turck CW et al (2003) The Drosophila myosin VI Jaguar is required for basal protein targeting and correct spindle orientation in mitotic neuroblasts. Dev Cell 4:273-281
35. Betschinger J, Mechtler K, Knoblich JJA (2003) The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature 422:326-330. doi: 10.1038/nature01486
36. Smith CA, Lau KM, Rahmani Z et al (2007) aPKC-mediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb. EMBO J 26:468-480. doi: 10.1038/sj.emboj.7601495
37. Lu B, Rothenberg M, Jan LY, Jan YN (1998) Partner of Numb colocalizes with Numb during mitosis and directs Numb asymmetric localization in Drosophila neural and muscle progenitors. Cell 95:225-235
38. Atwood SX, Prehoda KE (2009) aPKC phosphorylates Miranda to polarize fate determinants during neuroblast asymmetric cell division. Curr Biol 19:723-729. doi: 10.1016/j.cub.2009.03.056
39. Shen CP, Jan LY, Jan YN (1997) Miranda is required for the asymmetric localization of Prospero during mitosis in Drosophila. Cell 90:449-458
40. Ikeshima-Kataoka H, Skeath JB, Nabeshima Y et al (1997) Miranda directs Prospero to a daughter cell during Drosophila asymmetric divisions. Nature 390:625-629. doi: 10.1038/37641
41. Shen CP, Knoblich JA, Chan YM et al (1998) Miranda as a multidomain adapter linking apically localized Inscuteable and basally localized Staufen and Prospero during asymmetric cell division in Drosophila. Genes Dev 12:1837-1846
42. Matsuzaki F, Ohshiro T, Ikeshima-Kataoka H, Izumi H (1998) Miranda localizes staufen and prospero asymmetrically in mitotic neuroblasts and epithelial cells in early Drosophila embryogenesis. Development 125:4089-4098
43. Betschinger J, Mechtler K, Knoblich JA (2006) Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell 124:1241-1253. doi: 10.1016/j.cell.2006.01.038
44. Lee C-Y, Wilkinson BD, Siegrist SE et al (2006) Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Dev Cell 10:441-449. doi: 10.1016/j.devcel.2006.01.017
45. Li P, Yang X, Wasser M et al (1997) Inscuteable and Staufen mediate asymmetric localization and segregation of prospero RNA during Drosophila neuroblast cell divisions. Cell 90:437-447
46. Broadus J, Fuerstenberg S, Doe CQ (1998) Staufen-dependent localization of prospero mRNA contributes to neuroblast daughter-cell fate. Nature 391:792-795. doi: 10.1038/35861
47. Chu-Lagraff Q, Wright DM, McNeil LK, Doe CQ (1991) The prospero gene encodes a divergent homeodomain protein that controls neuronal identity in Drosophila. Development 2:79-85
48. Doe CQ, Chu-LaGraff Q, Wright DM, Scott MP (1991) The prospero gene specifies cell fates in the Drosophila central nervous system. Cell 65:451-464
49. Choksi SP, Southall TD, Bossing T et al (2006) Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells. Dev Cell 11:775-789. doi: 10.1016/j.devcel.2006.09.015
50. Bello B, Reichert H, Hirth F (2006) The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila. Development 133:2639-2648. doi: 10.1242/dev.02429
51. Qian X, Goderie SK, Shen Q et al (1998) Intrinsic programs of patterned cell lineages in isolated vertebrate CNS ventricular zone cells. Development 125:3143-3152
52. Qian X, Shen Q, Goderie SK et al (2000) Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells. Neuron 28:69-80
53. Aaku-Saraste E, Hellwig A, Huttner WB (1996) Loss of occludin and functional tight junctions, but not ZO-1, during neural tube closure-remodeling of the neuroepithelium prior to neurogenesis. Dev Biol 180:664-679. doi: 10.1006/dbio.1996.0336
54. Zhadanov AB, Provance DW, Speer CA et al (1999) Absence of the tight junctional protein AF-6 disrupts epithelial cell-cell junctions and cell polarity during mouse development. Curr Biol 9:880-888
55. Noctor SC, Martínez-Cerdeño V, Kriegstein AR (2008) Distinct behaviors of neural stem and progenitor cells underlie cortical neurogenesis. J Comput Neurol 508:28-44. doi: 10.1002/cne.21669
56. Miyata T, Kawaguchi A, Saito K et al (2004) Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Development 131:3133-3145. doi: 10.1242/dev.01173
57. Gal JS, Morozov YM, Ayoub AE et al (2006) Molecular and morphological heterogeneity of neural precursors in the mouse neocortical proliferative zones. J Neurosci 26:1045-1056. doi: 10.1523/JNEUROSCI.4499-05.2006
58. Hansen DV, Lui JH, Parker PRL, Kriegstein AR (2010) Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464:554-561
59. Fietz SA, Kelava I, Vogt J et al (2010) OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling. Nat Neurosci 13:690-699. doi: 10.1038/nn.2553
60. Wang X, Tsai J-W, LaMonica B, Kriegstein AR (2011) A new subtype of progenitor cell in the mouse embryonic neocortex. Nat Neurosci 14:555-561. doi: 10.1038/nn.2807
61. Shitamukai A, Konno D, Matsuzaki F (2011) Oblique radial glial divisions in the developing mouse neocortex induce self-renewing progenitors outside the germinal zone that resemble primate outer subventricular zone progenitors. J Neurosci 31:3683-3695. doi: 10.1523/JNEUROSCI.4773-10.2011
62. Manabe N, Hirai S-I, Imai F et al (2002) Association of ASIP/mPAR-3 with adherens junctions of mouse neuroepithelial cells. Dev Dyn 225:61-69. doi: 10.1002/dvdy.10139
63. Cappello S, Attardo A, Wu X et al (2006) The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface. Nat Neurosci 9:1099-1107. doi: 10.1038/nn1744
64. Chen L, Liao G, Yang L et al (2006) Cdc42 deficiency causes Sonic hedgehog-independent holoprosencephaly. Proc Natl Acad Sci USA 103:16520-16525. doi: 10.1073/pnas.0603533103
65. Imai F (2006) Inactivation of aPKC results in the loss of adherens junctions in neuroepithelial cells without affecting neurogenesis in mouse neocortex. Development 133:1855. doi: 10.1242/dev.02389
66. Marthiens V, ffrench-Constant C (2009) Adherens junction domains are split by asymmetric division of embryonic neural stem cells. EMBO Rep 10:515-520. doi: 10.1038/embor.2009.36
67. Kosodo Y, Röper K, Haubensak W et al (2004) Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells. EMBO J 23:2314-2324. doi: 10.1038/sj.emboj.7600223
68. Sykes AM, Huttner WB (2013) Prominin-1 (CD133) and the cell biology of neural progenitors and their progeny. Adv Exp Med Biol 777:89-98. doi: 10.1007/978-1-4614-5894-4-6
69. Bauer N, Fonseca A-V, Florek M et al (2008) New insights into the cell biology of hematopoietic progenitors by studying prominin-1 (CD133). Cells Tissues Organs 188:127-138. doi: 10.1159/000112847
70. Zacchigna S, Oh H, Wilsch-Bräuninger M et al (2009) Loss of the cholesterol-binding protein prominin-1/CD133 causes disk dysmorphogenesis and photoreceptor degeneration. J Neurosci 29:2297-2308. doi: 10.1523/JNEUROSCI. 2034-08.2009
71. Bultje RS, Castaneda-Castellanos DR, Jan LY et al (2009) Mammalian Par3 regulates progenitor cell asymmetric division via notch signaling in the developing neocortex. Neuron 63:189-202. doi: 10.1016/j.neuron.2009.07.004
72. Gaiano N, Nye JS, Fishell G (2000) Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 26:395-404
73. Rasin M-R, Gazula V-R, Breunig JJ et al (2007) Numb and Numbl are required for maintenance of cadherin-based adhesion and polarity of neural progenitors. Nat Neurosci 10:819-827. doi: 10.1038/nn1924
74. Konno D, Shioi G, Shitamukai A et al (2008) Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat Cell Biol 10:93-101. doi: 10.1038/ncb1673
75. Postiglione MP, Jüschke C, Xie Y et al (2011) Mouse inscuteable induces apical-basal spindle orientation to facilitate intermediate progenitor generation in the developing neocortex. Neuron 72:269-284. doi: 10.1016/j.neuron.2011.09.022
76. Haydar TF, Ang E, Rakic P (2003) Mitotic spindle rotation and mode of cell division in the developing telencephalon. Proc Natl Acad Sci USA 100:2890-2895. doi: 10.1073/pnas.0437969100
77. Du Q, Stukenberg PT, Macara IG (2001) A mammalian partner of inscuteable binds NuMA and regulates mitotic spindle organization. Nat Cell Biol 3:1069-1075. doi: 10.1038/ncb1201-1069
78. Wang X, Lui J, Kriegstein A (2011) Orienting fate: spatial regulation of neurogenic divisions. Neuron 72:191-193
79. Wang X, Tsai J-W, Imai JH et al (2009) Asymmetric centrosome inheritance maintains neural progenitors in the neocortex. Nature 461:947-955. doi: 10.1038/nature08435
80. Sakai D, Dixon J, Dixon MJ, Trainor PA (2012) Mammalian neurogenesis requires Treacle-Plk1 for precise control of spindle orientation, mitotic progression, and maintenance of neural progenitor cells. PLoS Genet 8:e1002566. doi: 10.1371/journal.pgen.1002566
81. Yamashita YM, Yuan H, Cheng J, Hunt AJ (2010) Polarity in stem cell division: asymmetric stem cell division in tissue homeostasis. CSH Perspect Biol 2:a001313. doi: 10.1101/cshperspect.a001313
82. Vessey JP, Amadei G, Burns SE et al (2012) An asymmetrically localized staufen2-dependent RNA complex regulates maintenance of Mammalian neural stem cells. Cell Stem Cell 11:517-528. doi: 10.1016/j.stem.2012.06.010
83. Kusek G, Campbell M, Doyle F et al (2012) Asymmetric segregation of the double-stranded RNA binding protein Staufen2 during mammalian neural stem cell divisions promotes lineage progression. Cell Stem Cell 11:505-516. doi: 10.1016/j.stem.2012.06.006
84. Dyer MA, Livesey FJ, Cepko CL, Oliver G (2003) Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Nat Genet 34:53-58. doi: 10.1038/ng1144
85. Schwamborn JC, Berezikov E, Knoblich JA (2009) The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell 136:913-925. doi: 10.1016/j.cell.2008.12.024
86. Sato T, Okumura F, Kano S et al (2011) TRIM32 promotes neural differentiation through retinoic acid receptor-mediated transcription. J Cell Sci 124:3492-3502. doi: 10.1242/jcs.088799
87. Hillje A-L, Worlitzer MMA, Palm T, Schwamborn JC (2011) Neural stem cells maintain their stemness through protein kinase C ζ-mediated inhibition of TRIM32. Stem Cells 29:1437-1447. doi: 10.1002/stem.687
88. Lange C, Huttner WB, Calegari F (2009) Cdk4/cyclinD1 overexpression in neural stem cells shortens G1, delays neurogenesis, and promotes the generation and expansion of basal progenitors. Cell Stem Cell 5:320-331. doi: 10.1016/j.stem.2009.05.026
89. Lim S, Kaldis P (2012) Loss of Cdk2 and Cdk4 induces a switch from proliferation to differentiation in neural stem cells. Stem Cells 30:1509-1520. doi: 10.1002/stem.1114
90. Tsunekawa Y, Britto JM, Takahashi M et al (2012) Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates. EMBO J 31:1879-1892. doi: 10.1038/emboj.2012.43
91. Glickstein SB, Alexander S, Ross ME (2007) Differences in cyclin D2 and D1 protein expression distinguish forebrain progenitor subsets. Cereb Cortex 17:632-642. doi: 10.1093/cercor/bhk008
92. Glickstein SB, Monaghan JA, Koeller HB et al (2009) Cyclin D2 is critical for intermediate progenitor cell proliferation in the embryonic cortex. J Neurosci 29:9614-9624. doi: 10.1523/JNEUROSCI.2284-09.2009
93. Voigt T (1989) Development of glial cells in the cerebral wall of ferrets: direct tracing of their transformation from radial glia into astrocytes. J Comput Neurol 289:74-88. doi: 10.1002/cne.902890106
94. Spassky N, Merkle FT, Flames N et al (2005) Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J Neurosci 25:10-18. doi: 10.1523/JNEUROSCI.1108-04.2005
95. Altman J (1969) Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comput Neurol 137:433-457. doi: 10.1002/cne.901370404
96. Luskin MB (1993) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11:173-189
97. Kaplan MS, Hinds JW (1977) Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197:1092-1094
98. Gage FH, Kempermann G, Palmer TD et al (1998) Multipotent progenitor cells in the adult dentate gyrus. J Neurobiol 36:249-266
99. Doetsch F, Caillé I, Lim DA et al (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703-716
100. Seri B, García-Verdugo JM, McEwen BS, Alvarez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:7153-7160
101. Doetsch F, García-Verdugo JM, Alvarez-Buylla A (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 17:5046-5061
102. Menn B, Garcia-Verdugo JM, Yaschine C et al (2006) Origin of oligodendrocytes in the subventricular zone of the adult brain. J Neurosci 26:7907-7918. doi: 10.1523/JNEUROSCI.1299-06.2006
103. Doetsch F, García-Verdugo JM, Alvarez-Buylla A (1999) Regeneration of a germinal layer in the adult mammalian brain. Proc Natl Acad Sci USA 96:11619-11624
104. Mirzadeh Z, Merkle FT, Soriano-Navarro M et al (2008) Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 3:265-278. doi: 10.1016/j.stem.2008. 07.004
105. Kuo CT, Mirzadeh Z, Soriano-Navarro M et al (2006) Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche. Cell 127:1253-1264. doi: 10.1016/j.cell.2006.10.041
106. Pastrana E, Cheng L-C, Doetsch F (2009) Simultaneous prospective purification of adult subventricular zone neural stem cells and their progeny. Proc Natl Acad Sci USA 106:6387-6392. doi: 10.1073/pnas.0810407106
107. Ponti G, Obernier K, Guinto C et al (2013) Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice. Proc Natl Acad Sci USA 110:E1045-E1054. doi: 10.1073/pnas.1219563110
108. Costa MR, Ortega F, Brill MS et al (2011) Continuous live imaging of adult neural stem cell division and lineage progression in vitro. Development 138:1057-1068. doi: 10.1242/dev.061663
109. Shen Q, Wang Y, Kokovay E et al (2008) Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell 3:289-300. doi: 10.1016/j.stem.2008.07.026
110. Andreu-Agulló C, Morante-Redolat JM, Delgado AC, Fariñas I (2009) Vascular niche factor PEDF modulates Notch-dependent stemness in the adult subependymal zone. Nat Neurosci 12:1514-1523. doi: 10.1038/nn.2437
111. Shen Q, Goderie SK, Jin L et al (2004) Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304:1338-1340
112. Lehtinen MK, Zappaterra MW, Chen X et al (2011) The cerebrospinal fluid provides a proliferative niche for neural progenitor cells. Neuron 69:893-905. doi: 10.1016/j.neuron.2011.01.023
113. Ferron SR, Pozo N, Laguna A et al (2010) Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling. Cell Stem Cell 7:367-379. doi: 10.1016/j.stem.2010.06.021
114. Sun Y, Goderie SK, Temple S (2005) Asymmetric distribution of EGFR receptor during mitosis generates diverse CNS progenitor cells. Neuron 45:873-886. doi: 10.1016/j.neuron.2005.01.045
115. Bignami A, Eng LF, Dahl D, Uyeda CT (1972) Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res 43:429-435
116. Barry D, McDermott K (2005) Differentiation of radial glia from radial precursor cells and transformation into astrocytes in the developing rat spinal cord. Glia 50:187-197. doi: 10.1002/glia.20166
117. Hirano M, Goldman JE (1988) Gliogenesis in rat spinal cord: evidence for origin of astrocytes and oligodendrocytes from radial precursors. J Neurosci Res 21:155-167. doi: 10.1002/jnr.490210208
118. Malatesta P, Hartfuss E, Götz M (2000) Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. Development 127:5253-5263
119. Zhu X, Bergles DE, Nishiyama A (2008) NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development 135:145-157. doi: 10.1242/dev.004895
120. Ge W-PP, Miyawaki A, Gage FH et al (2012) Local generation of glia is a major astrocyte source in postnatal cortex. Nature 484:376-380. doi: 10.1038/nature10959
121. Pringle NP, Richardson WD (1993) A singularity of PDGF alpha-receptor expression in the dorsoventral axis of the neural tube may define the origin of the oligodendrocyte lineage. Development 117:525-533
122. Zhou Q, Wang S, Anderson DJ (2000) Identification of a novel family of oligodendrocyte lineage-specific basic helix-loop-helix transcription factors. Neuron 25:331-343
123. Nishiyama A, Lin XH, Giese N et al (1996) Co-localization of NG2 proteoglycan and PDGF alpha-receptor on O2A progenitor cells in the developing rat brain. J Neurosci Res 43:299-314. doi: 10.1002/(SICI)1097-4547(19960201)43: 3<299:AID-JNR5>3.0.CO;2-E
124. Vallstedt A, Klos JM, Ericson J (2005) Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain. Neuron 45:55-67. doi: 10.1016/j.neuron.2004.12.026
125. Kessaris N, Fogarty M, Iannarelli P et al (2006) Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat Neurosci 9:173-179. doi: 10.1038/nn1620
126. Geha S, Pallud J, Junier M-P et al (2010) NG2+/Olig2+ cells are the major cycle-related cell population of the adult human normal brain. Brain Pathol 20:399-411. doi: 10.1111/j.1750-3639.2009.00295.x
127. Psachoulia K, Jamen F, Young KM, Richardson WD (2009) Cell cycle dynamics of NG2 cells in the postnatal and ageing brain. Neuron Glia Biol 5:57-67. doi: 10.1017/S1740925X09990354
128. Zhu X, Hill RA, Dietrich D et al (2011) Age-dependent fate and lineage restriction of single NG2 cells. Development 138:745-753. doi: 10.1242/dev.047951
129. Wade A, Robinson AE, Engler JR et al (2013) Proteoglycans and their roles in brain cancer. FEBS J. doi: 10.1111/febs.12109
130. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57-70
131. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646-674. doi: 10.1016/j.cell.2011.02.013
132. Lee C-Y, Robinson KJ, Doe CQ (2006) Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation. Nature 439:594-598. doi: 10.1038/nature04299
133. Gateff E (1978) Malignant neoplasms of genetic origin in Drosophila melanogaster. Science 200:1448-1459
134. Caussinus E, Gonzalez C (2005) Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet 37:1125-1129
135. Zyss D, Gergely F (2009) Centrosome function in cancer: guilty or innocent? Trends Cell Biol 19:334-346. doi: 10.1016/j.tcb.2009.04.001
136. Castellanos E, Dominguez P, Gonzalez C (2008) Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability. Curr Biol 18:1209-1214. doi: 10.1016/j.cub.2008.07.029
137. Basto R, Brunk K, Vinadogrova T et al (2008) Centrosome amplification can initiate tumorigenesis in flies. Cell 133:1032-1042
138. Read RD (2011) Drosophila melanogaster as a model system for human brain cancers. Glia 59:1364-1376. doi: 10.1002/glia.21148
139. Vogelstein B, Kinzler KW (2002) The genetic basis of human cancer. McGraw Hill, Toronto
140. Kunnev D, Ivanov I, Ionov Y (2009) Par-3 partitioning defective 3 homolog (C. elegans) and androgen-induced prostate proliferative shutoff associated protein genes are mutationally inactivated in prostate cancer cells. BMC Cancer 9:318. doi: 10.1186/1471-2407-9-318
141. Rothenberg SM, Mohapatra G, Rivera MN et al (2010) A genome-wide screen for microdeletions reveals disruption of polarity complex genes in diverse human cancers. Cancer Res 70:2158-2164. doi: 10.1158/0008-5472.CAN-09-3458
142. TCGA (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061-1068. doi: 10.1038/nature07385
143. Furnari FB, Fenton T, Bachoo RM et al (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21:2683-2710. doi: 10.1101/gad.1596707
144. Chen J, McKay RM, Parada LF (2012) Malignant glioma: lessons from genomics, mouse models, and stem cells. Cell 149:36-47. doi: 10.1016/j.cell.2012.03.009
145. Weiss WA, Burns MJ, Hackett C et al (2003) Genetic determinants of malignancy in a mouse model for oligodendroglioma. Cancer Res 63:1589-1595
146. Persson AI, Petritsch C, Swartling FJ et al (2010) Non-stem cell origin for oligodendroglioma. Cancer Cell 18:669-682. doi: 10.1016/j.ccr.2010.10.033
147. Klezovitch O, Fernandez TE, Tapscott SJ, Vasioukhin V (2004) Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice. Genes Dev 18:559-571. doi: 10.1101/gad.1178004
148. McCaffrey LM, Macara IG (2009) The Par3/aPKC interaction is essential for end bud remodeling and progenitor differentiation during mammary gland morphogenesis. Genes Dev 23:1450-1460. doi: 10.1101/gad.1795909
149. McCaffrey LM, Montalbano J, Mihai C, Macara IG (2012) Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis. Cancer Cell 22:601-614. doi: 10.1016/j.ccr.2012.10.003
150. Iden S, Riel WE, Schäfer R et al (2012) Tumor type-dependent function of the par3 polarity protein in skin tumorigenesis. Cancer Cell 22:389-403. doi: 10.1016/j.ccr.2012.08.004
151. Pece S, Serresi M, Santolini E et al (2004) Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. J Cell Biol 167:215-221. doi: 10.1083/jcb.200406140
152. Colaluca IN, Tosoni D, Nuciforo P et al (2008) NUMB controls p53 tumour suppressor activity. Nature 451:76-80. doi: 10.1038/nature06412
153. Ito T, Kwon HY, Zimdahl B et al (2010) Regulation of myeloid leukaemia by the cell-fate determinant Musashi. Nature 466:765-768. doi: 10.1038/nature09171
154. Duncan AW, Rattis FM, DiMascio LN et al (2005) Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 6:314-322. doi: 10.1038/ni1164
155. Kharas MG, Lengner CJ, Al-Shahrour F et al (2010) Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia. Nat Med 16:903-908. doi: 10.1038/nm.2187
156. Okabe M, Imai T, Kurusu M et al (2001) Translational repression determines a neuronal potential in Drosophila asymmetric cell division. Nature 411:94-98. doi: 10.1038/35075094
157. Sakakibara S, Imai T, Hamaguchi K et al (1996) Mouse-Musashi-1, a neural RNA-binding protein highly enriched in the mammalian CNS stem cell. Dev Biol 176:230-242
158. Imai T, Tokunaga A, Yoshida T et al (2001) The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA. Mol Cell Biol 21:3888-3900. doi: 10.1128/MCB.21.12. 3888-3900.2001
159. Gil-Perotin S, Marin-Husstege M, Li J et al (2006) Loss of p53 induces changes in the behavior of subventricular zone cells: implication for the genesis of glial tumors. J Neurosci 26:1107-1116. doi: 10.1523/JNEUROSCI.3970- 05.2006
160. Zheng H, Ying H, Yan H et al (2008) p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature 455:1129-1133. doi: 10.1038/nature07443
161. Wang Y, Yang J, Zheng H et al (2009) Expression of mutant p53 proteins implicates a lineage relationship between neural stem cells and malignant astrocytic glioma in a murine model. Cancer Cell 15:514-526. doi: 10.1016/j.ccr.2009.04.001
162. Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119:1420-1428. doi: 10.1172/JCI39104
163. Gunaratne A, Thai BL, Guglielmo GM (2012) Atypical PKC phosphorylates Par6 and facilitates TGFβ-induced EMT. Mol Cell Biol. doi: 10.1128/MCB.00837-12
164. Oft M, Peli J, Rudaz C et al (1996) TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev 10:2462-2477
165. Huber MA, Kraut N, Beug H (2005) Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol 17:548-558. doi: 10.1016/j.ceb.2005.08.001
166. Viloria-Petit AM, David L, Jia JY et al (2009) A role for the TGFbeta-Par6 polarity pathway in breast cancer progression. Proc Natl Acad Sci USA 106:14028-14033. doi: 10.1073/pnas.0906796106
167. Hills CE, Siamantouras E, Smith SW et al (2012) TGFβ modulates cell-to-cell communication in early epithelial-to-mesenchymal transition. Diabetologia 55:812-824. doi: 10.1007/s00125-011-2409-9
168. Murray NR, Jamieson L, Yu W et al (2004) Protein kinase Ciota is required for Ras transformation and colon carcinogenesis in vivo. J Cell Biol 164:797-802. doi: 10.1083/jcb.200311011
169. Cohen EEW, Lingen MW, Zhu B et al (2006) Protein kinase C zeta mediates epidermal growth factor-induced growth of head and neck tumor cells by regulating mitogen-activated protein kinase. Cancer Res 66:6296-6303. doi: 10.1158/0008-5472.CAN-05-3139
170. Aranda V, Haire T, Nolan ME et al (2006) Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control. Nat Cell Biol 8:1235-1245. doi: 10.1038/ncb1485
171. Martin-Belmonte F, Gassama A, Datta A et al (2007) PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42. Cell 128:383-397. doi: 10.1016/j.cell.2006.11.051
172. Xue B, Krishnamurthy K, Allred DC, Muthuswamy SK (2012) Loss of Par3 promotes breast cancer metastasis by compromising cell-cell cohesion. Nat Cell Biol 15:1-14. doi: 10.1038/ncb2663
173. Cunliffe HE, Jiang Y, Fornace KM et al (2012) PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer. Am J Cancer Res 2:478-491
174. Tomaić V, Gardiol D, Massimi P et al (2009) Human and primate tumour viruses use PDZ binding as an evolutionarily conserved mechanism of targeting cell polarity regulators. Oncogene 28:1-8. doi: 10.1038/onc.2008.365
175. Sipes NS, Feng Y, Guo F et al (2011) Cdc42 regulates extracellular matrix remodeling in three dimensions. J Biol Chem 286:36469-36477. doi: 10.1074/jbc.M111.283176
176. Alcantara Llaguno S, Chen J, Kwon C-H et al (2009) Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15:45-56. doi: 10.1016/j.ccr.2008.12.006
177. Liu C, Sage JC, Miller MR et al (2011) Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell 146:209-221. doi: 10.1016/j.cell.2011.06.014
178. Pei Y, Wechsler-Reya RJ (2010) A malignant oligarchy: progenitors govern the behavior of oligodendrogliomas. Cancer Cell 18:546-547. doi: 10.1016/j.ccr.2010.11.031
179. Bonavia R, Inda M-M, Cavenee WK, Furnari FB (2011) Heterogeneity maintenance in glioblastoma: a social network. Cancer Res 71:4055-4060. doi: 10.1158/0008-5472.CAN-11-0153
180. Visvader JE, Lindeman GJ (2008) Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8:755-768. doi: 10.1038/nrc2499
181. Singh SK, Clarke ID, Terasaki M et al (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821-5828
182. Singh SK, Hawkins C, Clarke ID et al (2004) Identification of human brain tumour initiating cells. Nature 432:396-401. doi: 10.1038/nature03128
183. Hemmati HD, Nakano I, Lazareff JA et al (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 100:15178-15183. doi: 10.1073/pnas.2036535100
184. Kelly JJ, Blough MD, Stechishin OD et al (2010) Oligodendroglioma cell lines containing t(1;19)(q10;p10). Neuro Oncol 12:745-755. doi: 10.1093/neuonc/noq031
185. Bao S, Wu Q, McLendon RE et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756-760. doi: 10.1038/nature05236
186. Tamura K, Aoyagi M, Wakimoto H et al (2010) Accumulation of CD133-positive glioma cells after high-dose irradiation by Gamma knife surgery plus external beam radiation. J Neurosurg 113:310-318. doi: 10.3171/2010.2. JNS091607
187. Li X, Lewis MT, Huang J et al (2008) Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst 100:672-679. doi: 10.1093/jnci/djn123
188. Oravecz-Wilson KI, Philips ST, Yilmaz OH et al (2009) Persistence of leukemia-initiating cells in a conditional knockin model of an imatinib-responsive myeloproliferative disorder. Cancer Cell 16:137-148. doi: 10.1016/j.ccr.2009.06.007
189. Chen J, Li Y, Yu T-S et al (2012) A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488:522-526. doi: 10.1038/nature11287
190. Wei Y, Jiang Y, Zou F et al (2013) Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells. Proc Natl Acad Sci USA 110:6829-6834. doi: 10.1073/pnas.1217002110
191. Jiang X, Xing H, Kim T-M et al (2012) Numb regulates glioma stem cell fate and growth by altering epidermal growth factor receptor and Skp1-Cullin-F-box ubiquitin ligase activity. Stem Cells 30:1313-1326. doi: 10.1002/stem.1120
192. Marumoto T, Tashiro A, Friedmann-Morvinski D et al (2009) Development of a novel mouse glioma model using lentiviral vectors. Nat Med 15:110-116. doi: 10.1038/nm.1863
193. Friedmann-Morvinski D, Bushong EA, Ke E et al (2012) Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice. Science 338:1080-1084. doi: 10.1126/science.1226929
194. Bischoff JR, Anderson L, Zhu Y et al (1998) A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J 17:3052-3065. doi: 10.1093/emboj/17.11.3052
195. Sen S, Zhou H, White RA (1997) A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene 14:2195-2200. doi: 10.1038/sj.onc.1201065
196. Tanner MM, Grenman S, Koul A et al (2000) Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. Clin Cancer Res 6:1833-1839
197. Sakakura C, Hagiwara A, Yasuoka R et al (2001) Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation. Br J Cancer 84:824-831. doi: 10.1054/bjoc.2000.1684
198. Sen S, Zhou H, Zhang R-D et al (2002) Amplification/overexpression of a mitotic kinase gene in human bladder cancer. J Natl Cancer Inst 94:1320-1329
199. Li D, Zhu J, Firozi PF et al (2003) Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. Clin Cancer Res 9:991-997
200. D'Assoro AB, Liu T, Quatraro C et al (2013) The mitotic kinase Aurora-A promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERα(+) breast cancer cells. Oncogene. doi: 10.1038/onc.2012.628
201. Do T-V, Xiao F, Bickel LE et al (2013) Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion. Oncogene. doi: 10.1038/onc.2012.632
202. Zhang H, Chen X, Liu B, Zhou L (2011) Effects of stable knockdown of Aurora kinase A on proliferation, migration, chromosomal instability, and expression of focal adhesion kinase and matrix metalloproteinase-2 in HEp-2 cells. Mol Cell Biochem 357:95-106. doi: 10.1007/s11010-011-0879-1
203. Huang F-J, You W-K, Bonaldo P et al (2010) Pericyte deficiencies lead to aberrant tumor vascularizaton in the brain of the NG2 null mouse. Dev Biol 344:1035-1046. doi: 10.1016/j.ydbio.2010.06.023
204. McAvoy S, Ganapathiraju SC, Ducharme-Smith AL et al (2007) Non-random inactivation of large common fragile site genes in different cancers. Cytogenet Genome Res 118:260-269. doi: 10.1159/000108309
205. Schimanski CC, Schmitz G, Kashyap A et al (2005) Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer. Oncogene 24:3100-3109. doi: 10.1038/sj.onc.1208520
206. Kuphal S, Wallner S, Schimanski CC et al (2006) Expression of Hugl-1 is strongly reduced in malignant melanoma. Oncogene 25:103-110. doi: 10.1038/sj.onc.1209008
207. Grifoni D, Garoia F, Schimanski C (2004) The human protein Hugl-1 substitutes for Drosophila lethal giant larvae tumour suppressor function in vivo. Oncogene 23:8688-8694. doi: 10.1038/sj.onc.1208023
208. Lisovsky M, Dresser K, Baker S et al (2009) Cell polarity protein Lgl2 is lost or aberrantly localized in gastric dysplasia and adenocarcinoma: an immunohistochemical study. Mod Pathol 22:977-984. doi: 10.1038/modpathol.2009.68
209. Spaderna S, Schmalhofer O, Wahlbuhl M et al (2008) The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res 68:537-544. doi: 10.1158/0008-5472.CAN-07-5682
210. Kashyap A, Zimmerman T, Ergül N et al (2013) The human Lgl polarity gene, Hugl-2, induces MET and suppresses Snail tumorigenesis. Oncogene 32:1396-1407. doi: 10.1038/onc.2012.162
211. Toda M, Iizuka Y, Yu W et al (2001) Expression of the neural RNA-binding protein Musashi1 in human gliomas. Glia 34:1-7
212. Potten CS, Booth C, Tudor GL et al (2003) Identification of a putative intestinal stem cell and early lineage marker; musashi-1. Differentiation 71:28-41
213. Götte M, Wolf M, Staebler A et al (2008) Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma. J Pathol 215:317-329. doi: 10.1002/path.2364
214. Muto J, Imai T, Ogawa D et al (2012) RNA-binding protein Musashi1 modulates glioma cell growth through the post-transcriptional regulation of Notch and PI3 kinase/Akt signaling pathways. PLoS ONE 7:e33431. doi: 10.1371/journal.pone.0033431
215. Sureban SM, May R, George RJ et al (2008) Knockdown of RNA binding protein musashi-1 leads to tumor regression in vivo. Gastroenterology 134:1448-1458. doi: 10.1053/j.gastro.2008.02.057
216. Westhoff B, Colaluca IN, D'Ario G et al (2009) Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci USA 106:22293-22298. doi: 10.1073/pnas.0907781106
217. Nolan ME, Aranda V, Lee S et al (2008) The polarity protein Par6 induces cell proliferation and is overexpressed in breast cancer. Cancer Res 68:8201-8209. doi: 10.1158/0008-5472.CAN-07-6567
218. Wolf G, Elez R, Doermer A et al (1997) Prognostic significance of polo-like kinase (PLK) expression in non-small cell lung cancer. Oncogene 14:543-549. doi: 10.1038/sj.onc.1200862
219. Weichert W, Ullrich A, Schmidt M et al (2006) Expression patterns of polo-like kinase 1 in human gastric cancer. Cancer Sci 97:271-276. doi: 10.1111/j.1349-7006.2006.00170.x
220. Takai N, Miyazaki T, Fujisawa K et al (2001) Expression of polo-like kinase in ovarian cancer is associated with histological grade and clinical stage. Cancer Lett 164:41-49
221. Weichert W, Schmidt M, Gekeler V et al (2004) Polo-like kinase 1 is overexpressed in prostate cancer and linked to higher tumor grades. Prostate 60:240-245. doi: 10.1002/pros.20050
222. Nogawa M, Yuasa T, Kimura S et al (2005) Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer. J Clin Invest 115:978-985. doi: 10.1172/JCI23043
223. Maire V, Némati F, Richardson M et al (2013) Polo-like kinase 1: a potential therapeutic option in combination with conventional chemotherapy for the management of patients with triple-negative breast cancer. Cancer Res 73:813-823. doi: 10.1158/0008-5472.CAN-12-2633
224. Knecht R, Elez R, Oechler M et al (1999) Prognostic significance of polo-like kinase (PLK) expression in squamous cell carcinomas of the head and neck. Cancer Res 59:2794-2797
225. Dietzmann K, Kirches E, Von Bossanyi P et al (2001) Increased human polo-like kinase-1 expression in gliomas. J Neurooncol 53:1-11
226. Lee C, Fotovati A, Triscott J et al (2012) Polo-like kinase 1 inhibition kills glioblastoma multiforme brain tumor cells in part through loss of SOX2 and delays tumor progression in mice. Stem Cells 30:1064-1075. doi: 10.1002/stem.1081
227. Regala RP, Weems C, Jamieson L et al (2005) Atypical protein kinase C iota is an oncogene in human non-small cell lung cancer. Cancer Res 65:8905-8911
228. Kojima Y, Akimoto K, Nagashima Y et al (2008) The overexpression and altered localization of the atypical protein kinase C lambda/iota in breast cancer correlates with the pathologic type of these tumors. Human Pathol 39:824-831. doi: 10.1016/j.humpath.2007.11.001
229. Eder AM, Sui X, Rosen DG et al (2005) Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer. Proc Natl Acad Sci USA 102:12519-12524. doi: 10.1073/pnas.0505641102
230. Ishiguro H, Akimoto K, Nagashima Y et al (2009) aPKClambda/iota promotes growth of prostate cancer cells in an autocrine manner through transcriptional activation of interleukin-6. Proc Natl Acad Sci USA 106:16369-16374. doi: 10.1073/pnas.0907044106
231. Regala RP, Weems C, Jamieson L et al (2005) Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity. J Biol Chem 280:31109-31115. doi: 10.1074/jbc.M505402200
232. Geevimaan K, Babu P (2013) Deregulation of cell polarity proteins in gliomagenesis. Evol Mol Biol Brain Tumors Ther Implic. doi: 10.5772/52365
233. Zhan L, Rosenberg A, Bergami KC et al (2008) Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma. Cell 135:865-878. doi: 10.1016/j.cell.2008.09.045
234. Boulay J-L, Stiefel U, Taylor E et al (2009) Loss of heterozygosity of TRIM3 in malignant gliomas. BMC Cancer 9:71. doi: 10.1186/1471-2407-9-71
235. Liu Y, Raheja R, Yeh N, et al (2013) TRIM3, a tumor suppressor linked to regulation of p21(Waf1/Cip1). Oncogene. doi: 10.1038/onc.2012.596