Abstract
Cell-extrinsic signals and intrinsic cell cycle regulators strictly control proliferation. Cancers develop from a cell that escapes these tight controls and proliferates unrestrictedly. The primary cilium critically controls proliferation by mediating cell-extrinsic signals and regulating cell cycle entry. Accordingly, recent studies showed that defective cilia can either promote or suppress cancers, depending on the cancer-initiating mutation, and that presence or absence of primary cilia is associated with specific cancer types. These novel findings suggest that primary cilia play central but distinct roles in different cancer types, opening up a completely new avenue of research to understand the biology and treatment of cancers.
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Alkuraya FS, Cai X, Emery C, Mochida GH, Al-Dosari MS, Felie JM, Hill RS, Barry BJ, Partlow JN, Gascon GG, Kentab A, Jan M, Shaheen R, Feng Y, Walsh CA (2011) Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected]. Am J Hum Genet 88:536–547
Altman J, Bayer SA (1997) Development of the cerebellar system: in relation to its evolution, structure, and functions. CRC Press, Boca Raton
Bakircioglu M et al (2011) The essential role of centrosomal NDE1 in human cerebral cortex neurogenesis. Am J Hum Genet 88:523–535
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760
Berbari NF, Kin NW, Sharma N, Michaud EJ, Kesterson RA, Yoder BK (2011) Mutations in Traf3ip1 reveal defects in ciliogenesis, embryonic development, and altered cell size regulation. Dev Biol 360:66–76
Bielas SL et al (2009) Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies. Nat Genet 41:1032–1036
Bishop CL, Bergin AM, Fessart D, Borgdorff V, Hatzimasoura E, Garbe JC, Stampfer MR, Koh J, Beach DH (2010) Primary cilium-dependent and -independent Hedgehog signaling inhibits p16(INK4A). Mol Cell 40:533–547
Bleau AM, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW, Holland EC (2009) PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell 4:226–235
Boehlke C, Kotsis F, Patel V, Braeg S, Voelker H, Bredt S, Beyer T, Janusch H, Hamann C, Godel M, Muller K, Herbst M, Hornung M, Doerken M, Kottgen M, Nitschke R, Igarashi P, Walz G, Kuehn EW (2010) Primary cilia regulate mTORC1 activity and cell size through Lkb1. Nat Cell Biol 12:1115–1122
Cano DA, Murcia NS, Pazour GJ, Hebrok M (2004) Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization. Development 131:3457–3467
Caspary T, Larkins CE, Anderson KV (2007) The graded response to Sonic Hedgehog depends on cilia architecture. Dev Cell 12:767–778
Chen MH, Wilson CW, Li YJ, Law KK, Lu CS, Gacayan R, Zhang X, Hui CC, Chuang PT (2009) Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved. Genes Dev 23:1910–1928
Chen J, McKay RM, Parada LF (2012) Malignant glioma: lessons from genomics, mouse models, and stem cells. Cell 149:36–47
Chizhikov VV, Davenport J, Zhang Q, Shih EK, Cabello OA, Fuchs JL, Yoder BK, Millen KJ (2007) Cilia proteins control cerebellar morphogenesis by promoting expansion of the granule progenitor pool. J Neurosci 27:9780–9789
Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H, Berhoukim R, Amani V, Goumnerova L, Eberhart CG, Lau CC, Olson JM, Gilbertson RJ, Gajjar A, Delattre O, Kool M, Ligon K, Meyerson M, Mesirov JP, Pomeroy SL (2011) Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol 29:1424–1430
Christensen ST, Clement CA, Satir P, Pedersen LB (2012) Primary cilia and coordination of receptor tyrosine kinase (RTK) signalling. J Pathol 226:172–184
Clark PA, Treisman DM, Ebben J, Kuo JS (2007) Developmental signaling pathways in brain tumor-derived stem-like cells. Dev Dyn 236:3297–3308
Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DY, Reiter JF (2005) Vertebrate Smoothened functions at the primary cilium. Nature 437:1018–1021
Corbit KC, Shyer AE, Dowdle WE, Gaulden J, Singla V, Chen MH, Chuang PT, Reiter JF (2008) Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms. Nat Cell Biol 10:70–76
Cortellino S, Wang C, Wang B, Bassi MR, Caretti E, Champeval D, Calmont A, Jarnik M, Burch J, Zaret KS, Larue L, Bellacosa A (2009) Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4. Dev Biol 325:225–237
Dahmane N, Ruiz i Altaba A (1999) Sonic hedgehog regulates the growth and patterning of the cerebellum. Development 126:3089–3100
Danilov AI, Gomes-Leal W, Ahlenius H, Kokaia Z, Carlemalm E, Lindvall O (2009) Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone. Glia 57:136–152
DiBella LM, Park A, Sun Z (2009) Zebrafish Tsc1 reveals functional interactions between the cilium and the TOR pathway. Hum Mol Genet 18:595–606
Dijkgraaf GJ, Alicke B, Weinmann L, Januario T, West K, Modrusan Z, Burdick D, Goldsmith R, Robarge K, Sutherlin D, Scales SJ, Gould SE, Yauch RL, de Sauvage FJ (2011) Small molecule inhibition of GDC-0449 refractory smoothened mutants and downstream mechanisms of drug resistance. Cancer Res 71:435–444
Ezratty EJ, Stokes N, Chai S, Shah AS, Williams SE, Fuchs E (2011) A role for the primary cilium in Notch signaling and epidermal differentiation during skin development. Cell 145:1129–1141
Fan S, Hurd TW, Liu CJ, Straight SW, Weimbs T, Hurd EA, Domino SE, Margolis B (2004) Polarity proteins control ciliogenesis via kinesin motor interactions. Curr Biol 14:1451–1461
Feng Y, Walsh CA (2004) Mitotic spindle regulation by Nde1 controls cerebral cortical size. Neuron 44:279–293
Firestone AJ, Weinger JS, Maldonado M, Barlan K, Langston LD, O’Donnell M, Gelfand VI, Kapoor TM, Chen JK (2012) Small-molecule inhibitors of the AAA + ATPase motor cytoplasmic dynein. Nature 484:125–129
Gerdes JM, Liu Y, Zaghloul NA, Leitch CC, Lawson SS, Kato M, Beachy PA, Beales PL, Demartino GN, Fisher S, Badano JL, Katsanis N (2007) Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response. Nat Genet 39(11):1350–1360
Gibson P et al (2010) Subtypes of medulloblastoma have distinct developmental origins. Nature 468:1095–1099
Goetz SC, Anderson KV (2010) The primary cilium: a signalling centre during vertebrate development. Nat Rev 11:331–344
Hallahan AR, Pritchard JI, Hansen S, Benson M, Stoeck J, Hatton BA, Russell TL, Ellenbogen RG, Bernstein ID, Beachy PA, Olson JM (2004) The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res 64:7794–7800
Han YG, Spassky N, Romaguera-Ros M, Garcia-Verdugo JM, Aguilar A, Schneider-Maunoury S, Alvarez-Buylla A (2008) Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat Neurosci 11:277–284
Han YG, Kim HJ, Dlugosz AA, Ellison DW, Gilbertson RJ, Alvarez-Buylla A (2009) Dual and opposing roles of primary cilia in medulloblastoma development. Nat Med 15:1062–1065
Hatten ME, Roussel MF (2011) Development and cancer of the cerebellum. Trends Neurosci 34:134–142
Hawkins CE, Bartels U, Bouffet E (2011) Molecular genetic approaches and potential new therapeutic strategies for pediatric diffuse intrinsic pontine glioma. J Clin Oncol 29:3956–3957
Haycraft CJ, Banizs B, Aydin-Son Y, Zhang Q, Michaud EJ, Yoder BK (2005) Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet 1:e53
Huang P, Schier AF (2009) Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia. Development 136:3089–3098
Huangfu D, Anderson KV (2005) Cilia and Hedgehog responsiveness in the mouse. Proc Natl Acad Sci USA 102:11325–11330
Huangfu D, Liu A, Rakeman AS, Murcia NS, Niswander L, Anderson KV (2003) Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426:83–87
Humke EW, Dorn KV, Milenkovic L, Scott MP, Rohatgi R (2010) The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins. Genes Dev 24:670–682
Jacoby M, Cox JJ, Gayral S, Hampshire DJ, Ayub M, Blockmans M, Pernot E, Kisseleva MV, Compere P, Schiffmann SN, Gergely F, Riley JH, Perez-Morga D, Woods CG, Schurmans S (2009) INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse. Nat Genet 41:1027–1031
Jia J, Kolterud A, Zeng H, Hoover A, Teglund S, Toftgard R, Liu A (2009) Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia. Dev Biol 330:452–460
Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH Jr, Scott MP (1996) Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science (NY) 272:1668–1671
Jonassen JA, San Agustin J, Follit JA, Pazour GJ (2008) Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle and cystic kidney disease. J Cell Biol 183:377–384
Jones C, Roper VC, Foucher I, Qian D, Banizs B, Petit C, Yoder BK, Chen P (2008) Ciliary proteins link basal body polarization to planar cell polarity regulation. Nat Genet 40:69–77
Kawauchi D, Robinson G, Uziel T, Gibson P, Rehg J, Gao C, Finkelstein D, Qu C, Pounds S, Ellison DW, Gilbertson RJ, Roussel MF (2012) A mouse model of the most aggressive subgroup of human medulloblastoma. Cancer Cell 21:168–180
Kim J, Lee JE, Heynen-Genel S, Suyama E, Ono K, Lee K, Ideker T, Aza-Blanc P, Gleeson JG (2010a) Functional genomic screen for modulators of ciliogenesis and cilium length. Nature 464:1048–1051
Kim SK, Shindo A, Park TJ, Oh EC, Ghosh S, Gray RS, Lewis RA, Johnson CA, Attie-Bittach T, Katsanis N, Wallingford JB (2010b) Planar cell polarity acts through septins to control collective cell movement and ciliogenesis. Science (NY) 329:1337–1340
Kim J, Dabiri S, Seeley ES (2011a) Primary cilium depletion typifies cutaneous melanoma in situ and malignant melanoma. PLoS One 6:e27410
Kim S, Zaghloul NA, Bubenshchikova E, Oh EC, Rankin S, Katsanis N, Obara T, Tsiokas L (2011b) Nde1-mediated inhibition of ciliogenesis affects cell cycle re-entry. Nat Cell Biol 13:351–360
Kim Y, Kim KH, Lee J, Lee YA, Kim M, Lee SJ, Park K, Yang H, Jin J, Joo KM, Nam DH (2012) Wnt activation is implicated in glioblastoma radioresistance. Lab Invest 92:466–473
Kisseleva MV, Cao L, Majerus PW (2002) Phosphoinositide-specific inositol polyphosphate 5-phosphatase IV inhibits Akt/protein kinase B phosphorylation and leads to apoptotic cell death. J Biol Chem 277:6266–6272
Knodler A, Feng S, Zhang J, Zhang X, Das A, Peranen J, Guo W (2010) Coordination of Rab8 and Rab11 in primary ciliogenesis. Proc Natl Acad Sci USA 107:6346–6351
Ko HW, Norman RX, Tran J, Fuller KP, Fukuda M, Eggenschwiler JT (2010) Broad-minded links cell cycle-related kinase to cilia assembly and hedgehog signal transduction. Dev Cell 18:237–247
Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, Troost D, Meeteren NS, Caron HN, Cloos J, Mrsic A, Ylstra B, Grajkowska W, Hartmann W, Pietsch T, Ellison D, Clifford SC, Versteeg R (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 3:e3088
Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137:216–233
Lam CW, Xie J, To KF, Ng HK, Lee KC, Yuen NW, Lim PL, Chan LY, Tong SF, McCormick F (1999) A frequent activated smoothened mutation in sporadic basal cell carcinomas. Oncogene 18:833–836
Li A, Saito M, Chuang JZ, Tseng YY, Dedesma C, Tomizawa K, Kaitsuka T, Sung CH (2011) Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors. Nat Cell Biol 13:402–411
Lin F, Hiesberger T, Cordes K, Sinclair AM, Goldstein LS, Somlo S, Igarashi P (2003) Kidney-specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease. Proc Natl Acad Sci USA 100:5286–5291
Liu A, Wang B, Niswander LA (2005) Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors. Development 132:3103–3111
Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810
Ma R, Li WP, Rundle D, Kong J, Akbarali HI, Tsiokas L (2005) PKD2 functions as an epidermal growth factor-activated plasma membrane channel. Mol Cell Biol 25:8285–8298
Mao J, Ligon KL, Rakhlin EY, Thayer SP, Bronson RT, Rowitch D, McMahon AP (2006) A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Cancer Res 66:10171–10178
May SR, Ashique AM, Karlen M, Wang B, Shen Y, Zarbalis K, Reiter J, Ericson J, Peterson AS (2005) Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli. Dev Biol 287:378–389
Monje M, Mitra SS, Freret ME, Raveh TB, Kim J, Masek M, Attema JL, Li G, Haddix T, Edwards MS, Fisher PG, Weissman IL, Rowitch DH, Vogel H, Wong AJ, Beachy PA (2011) Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma. Proc Natl Acad Sci USA 108:4453–4458
Moser JJ, Fritzler MJ, Rattner JB (2009) Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells. BMC Cancer 9:448
Nachury MV, Loktev AV, Zhang Q, Westlake CJ, Peranen J, Merdes A, Slusarski DC, Scheller RH, Bazan JF, Sheffield VC, Jackson PK (2007) A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell 129:1201–1213
Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, Bouffet E, Clifford SC, Hawkins CE, French P, Rutka JT, Pfister S, Taylor MD (2011) Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29:1408–1414
Ocbina PJ, Tuson M, Anderson KV (2009) Primary cilia are not required for normal canonical Wnt signaling in the mouse embryo. PLoS One 4:e6839
Parsons DW et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science (NY) 321:1807–1812
Pasca di Magliano M, Sekine S, Ermilov A, Ferris J, Dlugosz AA, Hebrok M (2006) Hedgehog/Ras interactions regulate early stages of pancreatic cancer. Genes Dev 20:3161–3173
Paugh BS, Broniscer A, Qu C, Miller CP, Zhang J, Tatevossian RG, Olson JM, Geyer JR, Chi SN, da Silva NS, Onar-Thomas A, Baker JN, Gajjar A, Ellison DW, Baker SJ (2011) Genome-wide analyses identify recurrent amplifications of receptor tyrosine kinases and cell-cycle regulatory genes in diffuse intrinsic pontine glioma. J Clin Oncol 29:3999–4006
Pei Y, Moore CE, Wang J, Tewari AK, Eroshkin A, Cho YJ, Witt H, Korshunov A, Read TA, Sun JL, Schmitt EM, Miller CR, Buckley AF, McLendon RE, Westbrook TF, Northcott PA, Taylor MD, Pfister SM, Febbo PG, Wechsler-Reya RJ (2012) An animal model of MYC-driven medulloblastoma. Cancer Cell 21:155–167
Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA (2007) HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 129:1351–1363
Rieder CL, Jensen CG, Jensen LC (1979) The resorption of primary cilia during mitosis in a vertebrate (PtK1) cell line. J Ultrastruct Res 68:173–185
Roessler E, Ermilov AN, Grange DK, Wang A, Grachtchouk M, Dlugosz AA, Muenke M (2005) A previously unidentified amino-terminal domain regulates transcriptional activity of wild-type and disease-associated human GLI2. Hum Mol Genet 14:2181–2188
Rohatgi R, Milenkovic L, Scott MP (2007) Patched1 regulates hedgehog signaling at the primary cilium. Science (NY) 317:372–376
Rosenbaum JL, Witman GB (2002) Intraflagellar transport. Nat Rev Mol Cell Biol 3:813–825
Ross AJ et al (2005) Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat Genet 37:1135–1140
Rossi M, Magnoni L, Miracco C, Mori E, Tosi P, Pirtoli L, Tini P, Oliveri G, Cosci E, Bakker A (2011) Beta-catenin and Gli1 are prognostic markers in glioblastoma. Cancer Biol Ther 11:753–761
Schneider L, Clement CA, Teilmann SC, Pazour GJ, Hoffmann EK, Satir P, Christensen ST (2005) PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts. Curr Biol 15:1861–1866
Schneider L, Stock CM, Dieterich P, Jensen BH, Pedersen LB, Satir P, Schwab A, Christensen ST, Pedersen SF (2009) The Na+/H+ exchanger NHE1 is required for directional migration stimulated via PDGFR-alpha in the primary cilium. J Cell Biol 185:163–176
Schraml P, Frew IJ, Thoma CR, Boysen G, Struckmann K, Krek W, Moch H (2009) Sporadic clear cell renal cell carcinoma but not the papillary type is characterized by severely reduced frequency of primary cilia. Mod Pathol 22:31–36
Schuller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG, Huillard E, Sun T, Ligon AH, Qian Y, Ma Q, Alvarez-Buylla A, McMahon AP, Rowitch DH, Ligon KL (2008) Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14:123–134
Seeley ES, Carriere C, Goetze T, Longnecker DS, Korc M (2009) Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia. Cancer Res 69:422–430
Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Kronig C, Schermer B, Benzing T, Cabello OA, Jenny A, Mlodzik M, Polok B, Driever W, Obara T, Walz G (2005) Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat Genet 37:537–543
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401
Spassky N, Han YG, Aguilar A, Strehl L, Besse L, Laclef C, Ros MR, Garcia-Verdugo JM, Alvarez-Buylla A (2008) Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool. Dev Biol 317:246–259
Spektor A, Tsang WY, Khoo D, Dynlacht BD (2007) Cep97 and CP110 suppress a cilia assembly program. Cell 130:678–690
Takebe N, Harris PJ, Warren RQ, Ivy SP (2011) Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol 8:97–106
Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, Eberhart CG, Parsons DW, Rutkowski S, Gajjar A, Ellison DW, Lichter P, Gilbertson RJ, Pomeroy SL, Kool M, Pfister SM (2012) Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123(4):465–472
TCGA (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068
Teilmann SC, Christensen ST (2005) Localization of the angiopoietin receptors Tie-1 and Tie-2 on the primary cilia in the female reproductive organs. Cell Biol Int 29:340–346
Thomas J, Morle L, Soulavie F, Laurencon A, Sagnol S, Durand B (2010) Transcriptional control of genes involved in ciliogenesis: a first step in making cilia. Biol Cell 102:499–513
Thompson MC, Fuller C, Hogg TL, Dalton J, Finkelstein D, Lau CC, Chintagumpala M, Adesina A, Ashley DM, Kellie SJ, Taylor MD, Curran T, Gajjar A, Gilbertson RJ (2006) Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol 24:1924–1931
Tran PV, Haycraft CJ, Besschetnova TY, Turbe-Doan A, Stottmann RW, Herron BJ, Chesebro AL, Qiu H, Scherz PJ, Shah JV, Yoder BK, Beier DR (2008) THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet 40:403–410
Tucker RW, Pardee AB, Fujiwara K (1979) Centriole ciliation is related to quiescence and DNA synthesis in 3 T3 cells. Cell 17:527–535
Tukachinsky H, Lopez LV, Salic A (2010) A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes. J Cell Biol 191:415–428
Verhaak RG et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110
Vitucci M, Hayes DN, Miller CR (2011) Gene expression profiling of gliomas: merging genomic and histopathological classification for personalised therapy. Br J Cancer 104:545–553
Wallace VA (1999) Purkinje-cell-derived Sonic Hedgehog regulates granule neuron precursor cell proliferation in the developing mouse cerebellum. Curr Biol 9:445–448
Wallingford JB (2010) Planar cell polarity signaling, cilia and polarized ciliary beating. Curr Opin Cell Biol 22:597–604
Wallingford JB, Mitchell B (2011) Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia. Genes Dev 25:201–213
Wang G, Krishnamurthy K, Bieberich E (2009) Regulation of primary cilia formation by ceramide. J Lipid Res 50:2103–2110
Wechsler-Reya RJ, Scott MP (1999) Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 22:103–114
Wheatley DN (1995) Primary cilia in normal and pathological tissues. Pathobiology: J Immunopathol Molecul Cell Biol 63:222–238
Willemarck N, Rysman E, Brusselmans K, Van Imschoot G, Vanderhoydonc F, Moerloose K, Lerut E, Verhoeven G, van Roy F, Vleminckx K, Swinnen JV (2010) Aberrant activation of fatty acid synthesis suppresses primary cilium formation and distorts tissue development. Cancer Res 70:9453–9462
Wong SY, Seol AD, So PL, Ermilov AN, Bichakjian CK, Epstein EH Jr, Dlugosz AA, Reiter JF (2009) Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis. Nat Med 15:1055–1061
Wu J, Du H, Wang X, Mei C, Sieck GC, Qian Q (2009) Characterization of primary cilia in human airway smooth muscle cells. Chest 136:561–570
Yang ZJ, Ellis T, Markant SL, Read TA, Kessler JD, Bourboulas M, Schuller U, Machold R, Fishell G, Rowitch DH, Wainwright BJ, Wechsler-Reya RJ (2008) Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell 14:135–145
Yauch RL, Dijkgraaf GJ, Alicke B, Januario T, Ahn CP, Holcomb T, Pujara K, Stinson J, Callahan CA, Tang T, Bazan JF, Kan Z, Seshagiri S, Hann CL, Gould SE, Low JA, Rudin CM, de Sauvage FJ (2009) Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science (NY 326:572–574
Yuan K, Frolova N, Xie Y, Wang D, Cook L, Kwon YJ, Steg AD, Serra R, Frost AR (2010) Primary cilia are decreased in breast cancer: analysis of a collection of human breast cancer cell lines and tissues. J Histochem Cytochem 58:857–870
Yuan S, Li J, Diener DR, Choma MA, Rosenbaum JL, Sun Z (2012) Target-of-rapamycin complex 1 (Torc1) signaling modulates cilia size and function through protein synthesis regulation. Proc Natl Acad Sci USA 109:2021–2026
Zarghooni M, Bartels U, Lee E, Buczkowicz P, Morrison A, Huang A, Bouffet E, Hawkins C (2010) Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. J Clin Oncol 28:1337–1344
Zeng H, Jia J, Liu A (2010) Coordinated translocation of mammalian Gli proteins and suppressor of fused to the primary cilium. PLoS One 5:e15900
Zhu D, Shi S, Wang H, Liao K (2009) Growth arrest induces primary-cilium formation and sensitizes IGF-1-receptor signaling during differentiation induction of 3 T3-L1 preadipocytes. J Cell Sci 122:2760–2768
Zuo X, Guo W, Lipschutz JH (2009) The exocyst protein Sec10 is necessary for primary ciliogenesis and cystogenesis in vitro. Mol Biol Cell 20:2522–2529
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American Lebanese Syrian Associated Charities (Y.-G.H.) and the Cancer Center Support Grant CA021765 from the National Cancer Institute (Y.-G.H.) supported this work.
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Hou, S., Han, YG. (2013). Primary Cilia and Brain Cancer. In: Tucker, K., Caspary, T. (eds) Cilia and Nervous System Development and Function. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5808-7_8
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