Mechanisms of Hedgehog signalling in cancer

References

• Adolphe C, Hetherington R, Ellis T, Wainwright B. 2006. Patched1 functions as a gatekeeper by promoting cell cycle progression. Cancer Res. 66:2081–2088.
   PubMed Web of Science ®Google Scholar
• Alcedo J, Ayzenzon M, Von Ohlen T, Noll M, Hooper JE. 1996. The Drosophila smoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal. Cell. 86:221–232.
   PubMed Web of Science ®Google Scholar
• Alexandre C, Jacinto A, Ingham PW. 1996. Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the Cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins. Genes Dev. 10:2003–2013.
   PubMed Web of Science ®Google Scholar
• Ayers KL, Therond PP. 2010. Evaluating Smoothened as a G-protein-coupled receptor for Hedgehog signalling. Trends Cell Biol. 20:287–298.
   Google Scholar
• Bai CB, Auerbach W, Lee JS, Stephen D, Joyner AL. 2002. Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway. Development. 129:4753–4761.
   PubMed Web of Science ®Google Scholar
• Bailey JM, Swanson BJ, Hamada T, Eggers JP, Singh PK, Caffery T, Ouellette MM, Hollingsworth MA. 2008. Sonic hedgehog promotes desmoplasia in pancreatic cancer. Clin Cancer Res. 14:5995–6004.
   PubMed Web of Science ®Google Scholar
• Bak M, Hansen C, Friis Henriksen K, Tommerup N. 2001. The human hedgehog-interacting protein gene: Structure and chromosome mapping to 4q31.21,Üíq31.3. Cytogenet Cell Genet. 92:300–303.
   PubMedGoogle Scholar
• Bar EE, Chaudhry A, Lin A, Fan X, Schreck K, Matsui W, Vescovi AL, Piccirillo S, Dimeco F, Olivi A, Eberhart CG. 2007. Cyclopamine-mediated Hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma. Stem Cells. 25:2524–2533.
   PubMed Web of Science ®Google Scholar
• Barnes EA, Kong M, Ollendorff V, Donoghue DJ. 2001. Patched1 interacts with cyclin B1 to regulate cell cycle progression. EMBO J. 20:2214–2223.
   PubMed Web of Science ®Google Scholar
• Beachy PA, Cooper MK, Young KE, Von Kessler DP, Park WJ, Hall TMT, Leahy DJ, Porter JA. 1997. Multiple roles of cholesterol in hedgehog protein biogenesis and signaling. Cold Spring Harb Symp Quant Biol. 62:191–204.
   PubMedGoogle Scholar
• Benazet J-D, Zeller R. 2009. Vertebrate limb development: Moving from classical morphogen gradients to an integrated 4-dimensional patterning system. Cold Spring Harbor Perspect Biol. 1:a001339.
   Web of Science ®Google Scholar
• Berman DM, Karhadkar SS, Maitra A, De Oca RM, Gerstenblith MR, Briggs K, Parker AR, Shimada Y, Eshleman JR, Watkins DN, Beachy PA. 2003. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 425:846–851.
   PubMed Web of Science ®Google Scholar
• Bhattacharya R, Kwon J, Ali B, Wang E, Patra S, Shridhar V, Mukherjee P. 2008. Role of hedgehog signaling in ovarian cancer. Clin Cancer Res. 14:7659–7666.
   PubMed Web of Science ®Google Scholar
• Bijlsma MF, Borensztajn KS, Roelink H, Peppelenbosch MP, Spek CA. 2007. Sonic hedgehog induces transcription-independent cytoskeletal rearrangement and migration regulated by arachidonate metabolites. Cell Signal. 19:2596–2604.
   PubMed Web of Science ®Google Scholar
• Bijlsma MF, Spek CA, Zivkovic D, van de Water S, Rezaee F, Peppelenbosch MP. 2006. Repression of smoothened by patched-dependent (pro-)vitamin D3 secretion. Plos Biology. 4:e232.
   PubMed Web of Science ®Google Scholar
• Binns W, James LF, Keeler RF, Balls LD. 1968. Effects of teratogenic agents in range plants. Cancer Res. 28:2323–2326.
   PubMed Web of Science ®Google Scholar
• Bourikas D, Pekarik V, Baeriswyl T, Grunditz A, Sadhu R, Nardo M, Stoeckli ET. 2005. Sonic hedgehog guides commissural axons along the longitudinal axis of the spinal cord. Nat Neurosci. 8:297–304.
   PubMed Web of Science ®Google Scholar
• Bumcrot DA, Takada R, McMahon AP. 1995. Proteolytic processing yields two secreted forms of sonic hedgehog. Mol Cell Biol. 15:2294–2303.
   PubMed Web of Science ®Google Scholar
• Buonamici S, Williams J, Morrissey M, Wang A, Guo R, Vattay A, Hsiao K, Yuan J, Green J, Ospina B, Yu Q, Ostrom L, Fordjour P, Anderson DL, Monahan JE, Kelleher JF, Peukert S, Pan S, Wu X, Maira S-M, García-Echeverría C, Briggs KJ, Watkins DN, Yao Y-m, Lengauer C, Warmuth M, Sellers WR, Dorsch M. 2010. Interfering with resistance to Smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma. Sci Trans Med. 2:51ra70.
   PubMed Web of Science ®Google Scholar
• Burke R, Nellen D, Bellotto M, Hafen E, Senti KA, Dickson BJ, Basler K. 1999. Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified Hedgehog from signaling cells. Cell. 99:803–815.
   PubMed Web of Science ®Google Scholar
• Carpenter D, Stone DM, Brush J, Ryan A, Armanini M, Frantz G, Rosenthal A, De Sauvage FJ. 1998. Characterization of two patched receptors for the vertebrate hedgehog protein family. Proc Natl Acad Sci USA. 95:13630–13634.
   PubMed Web of Science ®Google Scholar
• Charrier JB, Lapointe F, Le Douarin NM, Teillet MA. 2001. Anti-apoptotic role of Sonic hedgehog protein at the early stages of nervous system organogenesis. Development. 128:4011–4020.
   PubMed Web of Science ®Google Scholar
• Charytoniuk D, Porcel B, Rodriguez Gomez J, Faure H, Ruat M, Traiffort E. 2002. Sonic hedgehog signalling in the developing and adult brain. J Physiol Paris. 96:9–16.
   PubMedGoogle Scholar
• Chen JK, Taipale J, Cooper MK, Beachy PA. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 2002a; 16:2743–2748.
   PubMed Web of Science ®Google Scholar
• Chen JK, Taipale J, Young KE, Maiti T, Beachy PA. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci USA. 2002b; 99:14071–14076.
   PubMed Web of Science ®Google Scholar
• Chen W, Ren X-R, Nelson CD, Barak LS, Chen JK, Beachy PA, de Sauvage F, Lefkowitz RJ. 2004. Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2. Science. 306:2257–2260.
   PubMed Web of Science ®Google Scholar
• Chen W, Tang T, Eastham-Anderson J, Dunlap D, Alicke B, Nannini M, Gould S, Yauch R, Modrusan Z, DuPree KJ, Darbonne WC, Plowman G, De Sauvage FJ, Callahana CA. Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells. Proc Natl Acad Sci USA. 2011a; 108:9589–9594.
   PubMed Web of Science ®Google Scholar
• Chen Y, Struhl G. 1996. Dual roles for patched in sequestering and transducing Hedgehog. Cell. 87:553–563.
   PubMed Web of Science ®Google Scholar
• Chen Y, Struhl G. 1998. In vivo evidence that Patched and Smoothened constitute distinct binding and transducing components of a Hedgehog receptor complex. Development. 125:4943–4948.
   PubMed Web of Science ®Google Scholar
• Chen Y, Yue S, Xie L, Pu XH, Jin T, Cheng SY. Dual phosphorylation of suppressor of fused (Sufu) by PKA and GSK3beta regulates its stability and localization in the primary cilium. J Biol Chem. 2011b; 286:13502–13511.
   PubMed Web of Science ®Google Scholar
• Cheng SY, Bishop JM. 2002. Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex. Proc Natl Acad Sci USA. 99:5442–5447.
   PubMed Web of Science ®Google Scholar
• Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA. 1996. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature. 383:407–413.
   PubMed Web of Science ®Google Scholar
• Chiang C, Litingtung Y, Harris MP, Simandl BK, Li Y, Beachy PA, Fallon JF. 2001. Manifestation of the limb prepattern: Limb development in the absence of sonic hedgehog function. Dev Biol. 236:421–435.
   PubMed Web of Science ®Google Scholar
• Chidambaram A, Goldstein AM, Gailani MR, Gerrard B, Bale SJ, DiGiovanna JJ, Bale AE, Dean M. 1996. Mutations in the human homologue of the Drosophila patched gene in Caucasian and African-American nevoid basal cell carcinoma syndrome patients. Cancer Res. 56:4599–4601.
   PubMed Web of Science ®Google Scholar
• Chinchilla P, Xiao L, Kazanietz MG, Riobo NA. 2010. Hedgehog proteins activate pro-angiogenic responses in endothelial cells through non-canonical signaling pathways. Cell Cycle. 9:570–579.
   PubMed Web of Science ®Google Scholar
• Christensen ST, Pedersen LB, Schneider L, Satir P. 2007. Sensory cilia and integration of signal transduction in human health and disease. Traffic. 8:97–109.
   PubMed Web of Science ®Google Scholar
• Chuang P-T, McMahon AP. 1999. Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein. Nature. 397:617–621.
   PubMed Web of Science ®Google Scholar
• Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A. 2007. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol. 17:165–172.
   PubMed Web of Science ®Google Scholar
• Cohen MMJr. 2010. Hedgehog signaling: endocrine gland development and function. Am J Med Genetics Part A. 152A:238–244.
   PubMed Web of Science ®Google Scholar
• Copp AJ, Greene NDE. 2010. Genetics and development of neural tube defects. J Pathol. 220:217–230.
   PubMed Web of Science ®Google Scholar
• Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DYR, Reiter JF. 2005. Vertebrate Smoothened functions at the primary cilium. Nature. 437:1018–1021.
   PubMed Web of Science ®Google Scholar
• Corcoran RB, Scott MP. 2006. Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells. Proc Natl Acad Sci USA. 103:8408–8413.
   PubMed Web of Science ®Google Scholar
• Cui D, Xu Q, Wang K, Che X. 2010. Gli1 is a potential target for alleviating multidrug resistance of gliomas. J Neurol Sci. 288:156–166.
   PubMed Web of Science ®Google Scholar
• Dai P, Akimaru H, Tanaka Y, Maekawa T, Nakafuku M, Ishii S. 1999. Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3. J Biol Chem. 274:8143–8152.
   PubMed Web of Science ®Google Scholar
• Davies MN, Gloriam DE, Secker A, Freitas AA, Mendao M, Timmis J, Flower DR. 2007. Proteomic applications of automated GPCR classification. Proteomics. 7:2800–2814.
   PubMed Web of Science ®Google Scholar
• Dierks C, Beigi R, Guo GR, Zirlik K, Stegert MR, Manley P, Trussell C, Schmitt-Graeff A, Landwerlin K, Veelken H, Warmuth M. 2008. Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activation. Cancer Cell. 14:238–249.
   PubMed Web of Science ®Google Scholar
• Dierks C, Grbic J, Zirlik K, Beigi R, Englund NP, Guo GR, Veelken H, Engelhardt M, Mertelsmann R, Kelleher JF, Schultz P, Warmuth M. 2007. Essential role of stromally induced hedgehog signaling in B-cell malignancies. Nat Med. 13:944–951.
   PubMed Web of Science ®Google Scholar
• Drakopoulou E, Outram SV, Rowbotham NJ, Ross SE, Furmanski AL, Saldana JI, Hager-Theodorides AL, Crompton T. 2010. Non-redundant role for the transcription factor Gli1 at multiple stages of thymocyte development. Cell Cycle. 9:4144–4152.
   PubMed Web of Science ®Google Scholar
• Eaton S. 2008. Multiple roles for lipids in the Hedgehog signalling pathway. Nature Rev Mol Cell Biol. 9:437–445.
   PubMed Web of Science ®Google Scholar
• Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA, McMahon AP. 1993. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 75:1417–1430.
   PubMed Web of Science ®Google Scholar
• Ehlen HWA, Buelens LA, Vortkamp A. 2006. Hedgehog signaling in skeletal develoment. Birth Defects Res Part C Embryo Today Rev. 78:267–279.
   PubMedGoogle Scholar
• Eichberger T, Regl G, Ikram MS, Neill GW, Philpott MP, Aberger F, Frischauf AM. 2004. FOXE1, a new transcriptional target of GLI2, is expressed in human epidermis and basal cell carcinoma. J Invest Dermatol. 122:1180–1187.
   PubMed Web of Science ®Google Scholar
• Epstein DJ, Marti E, Scott MP, McMahon AP. 1996. Antagonizing cAMP-dependent protein kinase A in the dorsal CNS activates a conserved Sonic hedgehog signaling pathway. Development. 122:2885–2894.
   PubMedGoogle Scholar
• Ericson J, Morton S, Kawakami A, Roelink H, Jessell TM. 1996. Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity. Cell. 87:661–673.
   PubMed Web of Science ®Google Scholar
• Fan CM, Porter JA, Chiang C, Chang DT, Beachy PA, Tessier-Lavigne M. 1995. Long-range sclerotome induction by sonic hedgehog: Direct role of the amino-terminal cleavage product and modulation by the cyclic AMP signaling pathway. Cell. 81:457–465.
   PubMed Web of Science ®Google Scholar
• Fan L, Pepicelli CV, Dibble CC, Catbagan W, Zarycki JL, Laciak R, Gipp J, Shaw A, Lamm MLG, Munoz A, Lipinski R, Thrasher JB, Bushman W. 2004. Hedgehog signaling promotes prostate xenograft tumor growth. Endocrinology. 145:3961–3970.
   PubMed Web of Science ®Google Scholar
• Forbes AJ, Nakano Y, Taylor AM, Ingham PW. 1993. Genetic analysis of hedgehog signalling in the Drosophila embryo. Development. 119:115–124.
   Google Scholar
• Fuccillo M, Joyner AL, Fishell G. 2006. Morphogen to mitogen: The multiple roles of hedgehog signalling in vertebrate neural development. Nature Rev Neurosci. 7:772–783.
   PubMed Web of Science ®Google Scholar
• Gailani MR, Stahle-Backdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, Unden AB, Dean M, Brash DE, Bale AE, Toftgard R. 1996. The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Genet. 14:78–81.
   PubMed Web of Science ®Google Scholar
• Gallet A. 2011. Hedgehog morphogen: From secretion to reception. Trends Cell Biol. 21:238–246.
   PubMed Web of Science ®Google Scholar
• Gallet A, Therond PP. 2005. Temporal modulation of the Hedgehog morphogen gradient by a patched-dependent targeting to lysosomal compartment. Dev Biol. 277:51–62.
   PubMed Web of Science ®Google Scholar
• Gallet A, Rodriguez R, Ruel L, Therond PP. 2003. Cholesterol modification of Hedgehog is required for trafficking and movement, revealing an asymmetric cellular response to Hedgehog. Developmental Cell. 4:191–204.
   PubMed Web of Science ®Google Scholar
• Gill PS, Rosenblum ND. 2006. Control of murine kidney development by sonic hedgehog and its GLI effectors. Cell Cycle. 5:1426–1430.
   PubMed Web of Science ®Google Scholar
• Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE. 1996. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. 85:841–851.
   PubMed Web of Science ®Google Scholar
• Hatsell S, Frost AR. 2007. Hedgehog signaling in mammary gland development and breast cancer. J Mammary Gland Biol Neoplasia. 12:163–173.
   PubMed Web of Science ®Google Scholar
• Hoseong Yang S, Andl T, Grachtchouk V, Wang A, Liu J, Syu LJ, Ferris J, Wang TS, Glick AB, Millar SE, Dlugosz AA. 2008. Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/beta-catenin signaling. Nat Genet. 40:1130–1135.
   PubMed Web of Science ®Google Scholar
• Huangfu D, Anderson KV. 2006. Signaling from Smo to Ci/Gli: Conservation and divergence of Hedgehog pathways from Drosophila to vertebrates. Development. 133:3–14.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Hui CC, Slusarski D, Platt KA, Holmgren R, Joyner AL. 1994. Expression of three mouse homologs of the Drosophila segment polarity gene cubitus interruptus, Gli, Gli-2, and Gli-3, in ectoderm- and mesoderm-derived tissues suggests multiple roles during postimplantation development. Dev Biol. 162:402–413.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Huntzicker EG, Estay IS, Zhen H, Lokteva LA, Jackson PK, Oro AE. 2006. Dual degradation signals control Gli protein stability and tumor formation. Genes Dev. 20:276–281.
   PubMed Web of Science ®Google Scholar
• Hynes M, Ye W, Wang K, Stone D, Murone M, De Sauvage F, Rosenthal A. 2000. The seven-transmembrane receptor Smoothened cell-autonomously induces multiple ventral cell types. Nat Neurosci. 3:41–46.
   PubMed Web of Science ®Google Scholar
• Ikram MS, Neill GW, Regl G, Eichberger T, Frischauf AM, Aberger F, Quinn A, Philpott M. 2004. GLI2 is expressed in normal human epidermis and BCC and induces GLI1 expression by binding to its promoter. J Invest Dermatol. 122:1503–1509.
   PubMed Web of Science ®Google Scholar
• Incardona JP, Gruenberg J, Roelink H. 2002. Sonic hedgehog induces the segregation of patched and smoothened in endosomes. Curr Biol. 12:983–995.
   PubMed Web of Science ®Google Scholar
• Ingham PW, Taylor AM, Nakano Y. 1991. Role of the Drosophila patched gene in positional signalling. Nature. 353:184–187.
   PubMed Web of Science ®Google Scholar
• Iwasaki M, Le AX, Helms JA. 1997. Expression of indian hedgehog, bone morphogenetic protein 6 and gli during skeletal morphogenesis. Mech Dev. 69:197–202.
   PubMed Web of Science ®Google Scholar
• Jenkins D. 2009. Hedgehog signalling: emerging evidence for non-canonical pathways. Cell Signal. 21:1023–1034.
   PubMed Web of Science ®Google Scholar
• Jenkins D, Winyard PJD, Woolf AS. 2007. Immunohistochemical analysis of Sonic hedgehog signalling in normal human urinary tract development. J Anat. 211:620–629.
   PubMed Web of Science ®Google Scholar
• Ji Z, Mei FC, Xie J, Cheng X. 2007. Oncogenic KRAS activates hedgehog signaling pathway in pancreatic cancer cells. J Biol Chem. 282:14048–14055.
   PubMed Web of Science ®Google Scholar
• Jia J, Tong C, Jiang J. 2003. Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail. Genes Dev. 17:2709–2720.
   PubMed Web of Science ®Google Scholar
• Jia J, Tong C, Wang B, Luo L, Jiang J. 2004. Hedgehog signalling activity of smoothened requires phosphorylation by protein kinase A and casein kinase I. Nature. 432:1045–1050.
   PubMed Web of Science ®Google Scholar
• Johnson RW, Nguyen MP, Padalecki SS, Grubbs BG, Merkel AR, Oyajobi BO, Matrisian LM, Mundy GR, Sterling JA. 2011. TGF-beta promotion of Gli2-induced expression of parathyroid hormone-related protein, an important osteolytic factor in bone metastasis, is independent of canonical Hedgehog signaling. Cancer Res. 71:822–831.
   PubMed Web of Science ®Google Scholar
• Karhadkar SS, Bova GS, Abdallah N, Dhara S, Gardner D, Maitra A, Isaacs JT, Berman DM, Beachy PA. 2004. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature. 431:707–712.
   PubMed Web of Science ®Google Scholar
• Kawakami T, Kawcak TN, Li YJ, Zhang W, Hu Y, Chuang PT. 2002. Mouse dispatched mutants fail to distribute hedgehog proteins and are defective in hedgehog signaling. Development. 129:5753–5765.
   PubMed Web of Science ®Google Scholar
• King PJ, Guasti L, Laufer E. 2008. Hedgehog signalling in endocrine development and disease. J Endocrinol. 198:439–450.
   PubMed Web of Science ®Google Scholar
• Kinzler KW, Bigner SH, Bigner DD, Trent JM, Law ML, O'Brien SJ, Wong AJ, Vogelstein B. 1987. Identification of an amplified, highly expressed gene in a human glioma. Science. 236:70–73.
   PubMed Web of Science ®Google Scholar
• Korc M. 2007. Pancreatic cancer-associated stroma production. Am J Surg. 194:S84–S86.
   PubMed Web of Science ®Google Scholar
• Kubo M, Nakamura M, Tasaki A, Yamanaka N, Nakashima H, Nomura M, Kuroki S, Katano M. 2004. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res. 64:6071–6074.
   PubMed Web of Science ®Google Scholar
• Kump E, Ji J, Wernli M, Hausermann P, Erb P. 2008. Gli2 upregulates cFlip and renders basal cell carcinoma cells resistant to death ligand-mediated apoptosis. Oncogene. 27:3856–3864.
   PubMed Web of Science ®Google Scholar
• Lauth M, Bergstrom A, Shimokawa T, Toftgard R. 2007. Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc Natl Acad Sci USA. 104:8455–8460.
   PubMed Web of Science ®Google Scholar
• Lee J, Ekker SC, Von Kessler DP, Porter JA, Sun BI, Beachy PA. 1994. Autoproteolysis in hedgehog protein biogenesis. Science. 266:1528–1537.
   PubMed Web of Science ®Google Scholar
• Lee Y, Miller HL, Russell HR, Boyd K, Curran T, McKinnon PJ. 2006. Patched2 modulates tumorigenesis in Patched1 heterozygous mice. Cancer Res. 66:6964–6971.
   PubMed Web of Science ®Google Scholar
• Lindemann RK. 2008. Stroma-initiated Hedgehog signaling takes center stage in B-cell lymphoma. Cancer Res. 68:961–964.
   PubMed Web of Science ®Google Scholar
• Lipinski RJ, Song C, Sulik KK, Everson JL, Gipp JJ, Yan D, Bushman W, Rowland IJ. 2010. Cleft lip and palate results from Hedgehog signaling antagonism in the mouse: Phenotypic characterization and clinical implications. Birth Defects Res. 88:232–240.
   PubMed Web of Science ®Google Scholar
• Litingtung Y, Lei L, Westphal H, Chiang C. 1998. Sonic hedgehog is essential to foregut development. Nat Genet. 20:58–61.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, Suri P, Wicha MS. 2006. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 66:6063–6071.
   PubMed Web of Science ®Google Scholar
• Low W-C, Wang C, Pan Y, Huang X-Y, Chen JK, Wang B. 2008. The decoupling of Smoothened from Galphai proteins has little effect on Gli3 protein processing and Hedgehog-regulated chick neural tube patterning. Dev Biol. 321:188–196.
   PubMed Web of Science ®Google Scholar
• Lum L, Zhang C, Oh S, Mann RK, Von Kessler DP, Taipale J, Weis-Garcia F, Gong R, Wang B, Beachy PA. 2003. Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2. Mol Cell. 12:1261–1274.
   PubMed Web of Science ®Google Scholar
• MacDonald TJ, Brown KM, Lafleur B, Peterson K, Lawlor C, Chen Y, Packer RJ, Cogen P, Stephan DA. 2001. Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat Genet. 29:143–152.
   PubMed Web of Science ®Google Scholar
• Mao J, Kim B-M, Rajurkar M, Shivdasani RA, McMahon AP. 2010. Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract. Development. 137:1721–1729.
   PubMed Web of Science ®Google Scholar
• Marigo V, Tabin CJ. 1996. Regulation of patched by Sonic hedgehog in the developing neural tube. Proc Natl Acad Sci USA. 93:9346–9351.
   PubMed Web of Science ®Google Scholar
• Marigo V, Johnson RL, Vortkamp A, Tabin CJ. Sonic hedgehog differentially regulates expression of GLI and GLI3 during limb development. Dev Biol. 1996a; 180:273–283.
   PubMed Web of Science ®Google Scholar
• Marigo V, Davey RA, Zuo Y, Cunningham JM, Tabin CJ. Biochemical evidence that patched is the hedgehog receptor. Nature. 1996b; 384:176–179.
   PubMed Web of Science ®Google Scholar
• Marigo V, Laufer E, Nelson CE, Riddle RD, Johnson RL, Tabin C. Sonic hedgehog regulates patterning in early embryos. Biochem Soc Symp. 1996c; 62:51–60.
   PubMedGoogle Scholar
• Merchant AA, Matsui W. 2010. Targeting Hedgehog - a cancer stem cell pathway. Clin Cancer Res. 16:3130–3140.
   PubMed Web of Science ®Google Scholar
• Michael LE, Westerman BA, Ermilov AN, Wang A, Ferris J, Liu J, Blom M, Ellison DW, Van Lohuizen M, Dlugosz AA. 2008. Bmi1 is required for hedgehog pathway-driven medulloblastoma expansion. Neoplasia. 10:1343–1349.
   PubMed Web of Science ®Google Scholar
• Mille F, Thibert C, Fombonne J, Rama N, Guix C, Hayashi H, Corset V, Reed JC, Mehlen P. 2009. The Patched dependence receptor triggers apoptosis through a DRAL-caspase-9 complex. Nature Cell Biol. 11:739–746.
   PubMed Web of Science ®Google Scholar
• Motoyama J, Takabatake T, Takeshima K, Hui CC. 1998. Ptch2, a second mouse Patched gene is co-expressed with Sonic hedgehog. Nat Genet. 18:104–106.
   PubMed Web of Science ®Google Scholar
• Murone M, Luoh SM, Stone D, Li W, Gurney A, Armanini M, Grey C, Rosenthal A, De Sauvage FJ. 2000. Gli regulation by the opposing activities of fused and suppressor of fused. Nature Cell Biol. 2:310–312.
   PubMed Web of Science ®Google Scholar
• Nakamura K, Sasajima J, Mizukami Y, Sugiyama Y, Yamazaki M, Fujii R, Kawamoto T, Koizumi K, Sato K, Fujiya M, Sasaki K, Tanno S, Okumura T, Shimizu N, Kawabe J, Karasaki H, Kono T, Ii M, Bardeesy N, Chung DC, Kohgo Y. 2010. Hedgehog promotes neovascularization in pancreatic cancers by regulating Ang-1 and IGF-1 expression in bone-marrow derived pro-angiogenic cells. PLoS ONE. 5:e8824.
   PubMed Web of Science ®Google Scholar
• Nanni L, Ming JE, Bocian M, Steinhaus K, Bianchi DW, Die-Smulders C, Giannotti A, Imaizumi K, Jones KL, Campo MD, Martin RA, Meinecke P, Pierpont ME, Robin NH, Young ID, Roessler E, Muenke M. 1999. The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. Hum Mol Genet. 8:2479–2488.
   PubMed Web of Science ®Google Scholar
• Nusslein-Volhard C, Wieschaus E. 1980. Mutations affecting segment number and polarity in Drosophila. Nature. 287:795–801.
   PubMed Web of Science ®Google Scholar
• Ocbina PJR, Anderson KV. 2008. Intraflagellar transport, cilia, and mammalian Hedgehog signaling: analysis in mouse embryonic fibroblasts. Dev Dyn. 237:2030–2038.
   PubMed Web of Science ®Google Scholar
• Ogden SK, Ascano MJr, Stegman MA, Suber LM, Hooper JE, Robbins DJ. 2003. Identification of a functional interaction between the transmembrane protein Smoothened and the kinesin-related protein Costal2. Curr Biol. 13:1998–2003.
   PubMed Web of Science ®Google Scholar
• Ogden SK, Fei DL, Schilling NS, Ahmed YF, Hwa J, Robbins DJ. 2008. G protein Galphai functions immediately downstream of Smoothened in Hedgehog signalling. Nature. 456:967–970.
   Google Scholar
• Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, Frese KK, DeNicola G, Feig C, Combs C, Winter SP, Ireland-Zecchini H, Reichelt S, Howat WJ, Chang A, Dhara M, Wang L, Rückert F, Grützmann R, Pilarsky C, Izeradjene K, Hingorani SR, Huang P, Davies SE, Plunkett W, Egorin M, Hruban RH, Whitebread N, McGovern K, Adams J, Iacobuzio-Donahue C, Griffiths J, Tuveson DA. 2009. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 324:1457–1461.
   PubMed Web of Science ®Google Scholar
• Osterlund T, Kogerman P. 2006. Hedgehog signalling: how to get from Smo to Ci and Gli. Trends Cell Biol. 16:176–180.
   PubMed Web of Science ®Google Scholar
• Pan Y, Bai CB, Joyner AL, Wang B. 2006. Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation. Mol Cell Biol. 26:3365–3377.
   PubMed Web of Science ®Google Scholar
• Park HL, Bai C, Platt KA, Matise MP, Beeghly A, Hui CC, Nakashima M, Joyner AL. 2000. Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation. Development. 127:1593–1605.
   PubMed Web of Science ®Google Scholar
• Peacock CD, Wang Q, Gesell GS, Corcoran-Schwartz IM, Jones E, Devereux WL, Rhodes JT, Huff CA, Beachy PA, Watkins DN, Matsui W. 2007. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci USA. 104:4048–4053.
   PubMed Web of Science ®Google Scholar
• Pepicelli CV, Lewis PM, McMahon AP. 1998. Sonic hedgehog regulates branching morphogenesis in the mammalian lung. Curr Biol. 8:1083–1086.
   PubMed Web of Science ®Google Scholar
• Pepinsky RB, Zeng C, Went D, Rayhorn P, Baker DP, Williams KP, Bixler SA, Ambrose CM, Garber EA, Miatkowski K, Taylor FR, Wang EA, Galdes A. 1998. Identification of a palmitic acid-modified form of human Sonic hedgehog. J Biol Chem. 273:14037–14045.
   PubMed Web of Science ®Google Scholar
• Peukert S, Jain RK, Geisser A, Sun Y, Zhang R, Bourret A, Carlson A, DaSilva J, Ramamurthy A, Kelleher JF. 2009. Identification and structure-activity relationships of ortho-biphenyl carboxamides as potent Smoothened antagonists inhibiting the Hedgehog signaling pathway. Bioorg Med Chem Lett. 19:328–331.
   PubMed Web of Science ®Google Scholar
• Porter JA, Young KE, Beachy PA. 1996. Cholesterol modification of hedgehog signaling proteins in animal development. Science. 274:255–259 [Erratum appears in Science 1996 Dec 6;274(5293):1597].
   PubMed Web of Science ®Google Scholar
• Porter JA, Von Kessler DP, Ekker SC, Young KE, Lee JJ, Moses K, Beachy PA. 1995. The product of hedgehog autoproteolytic cleavage active in local and long-range signalling. Nature. 374:363–366.
   PubMed Web of Science ®Google Scholar
• Price MA, Kalderon D. 2002. Proteolysis of the Hedgehog signaling effector Cubitus interruptus requires phosphorylation by glycogen synthase kinase 3 and casein kinase 1. Cell. 108:823–835.
   PubMed Web of Science ®Google Scholar
• Queiroz KCS, Ruela-De-Sousa RR, Fuhler GM, Aberson HL, Ferreira CV, Peppelenbosch MP, Spek CA. 2010. Hedgehog signaling maintains chemoresistance in myeloid leukemic cells. Oncogene. 29:6314–6322.
   PubMed Web of Science ®Google Scholar
• Rahnama F, Shimokawa T, Lauth M, Finta C, Kogerman P, Teglund S, Toftgard R, Zaphiropoulos PG. 2006. Inhibition of GLI1 gene activation by Patched1. Biochem J. 394:19–26.
   PubMed Web of Science ®Google Scholar
• Rao PH, Houldsworth J, Dyomina K, Parsa NZ, Cigudosa JC, Louie DC, Popplewell L, Offit K, Jhanwar SC, Chaganti RSK. 1998. Chromosomal and gene amplification in diffuse large B-cell lymphoma. Blood. 92:234–240.
   PubMed Web of Science ®Google Scholar
• Regl G, Neill GW, Eichberger T, Kasper M, Ikram MS, Koller J, Hintner H, Quinn AG, Frischauf AM, Aberger F. 2002. Human GLI2 and GLI1 are part of a positive feedback mechanism in basal cell carcinoma. Oncogene. 21:5529–5539.
   PubMed Web of Science ®Google Scholar
• Regl G, Kasper M, Schnidar H, Eichberger T, Neill GW, Philpott MP, Esterbauer H, Hauser-Kronberger C, Frischauf A-M, Aberger F. 2004. Activation of the BCL2 promoter in response to Hedgehog/GLI signal transduction is predominantly mediated by GLI2. Cancer Res. 64:7724–7731.
   PubMed Web of Science ®Google Scholar
• Renault MA, Roncalli J, Tongers J, Thorne T, Klyachko E, Misener S, Volpert OV, Mehta S, Burg A, Luedemann C, Qin G, Kishore R, Losordo DW. 2010. Sonic hedgehog induces angiogenesis via Rho kinase-dependent signaling in endothelial cells. J Mol Cell Cardiol. 49:490–498.
   PubMed Web of Science ®Google Scholar
• Reya T, Morrison SJ, Clarke MF, Weissman IL. 2001. Stem cells, cancer, and cancer stem cells. Nature. 414:105–111.
   PubMed Web of Science ®Google Scholar
• Ribes V, Balaskas N, Sasai N, Cruz C, Dessaud E, Cayuso J, Tozer S, Yang LL, Novitch B, Marti E, Briscoe J. 2010. Distinct Sonic Hedgehog signaling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube. Genes Dev. 24:1186–1200.
   PubMed Web of Science ®Google Scholar
• Riddle RD, Johnson RL, Laufer E, Tabin C. 1993. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell. 75:1401–1416.
   PubMed Web of Science ®Google Scholar
• Riobo NA, Saucy B, Dilizio C, Manning DR. Activation of heterotrimeric G proteins by Smoothened. Proc Natl Acad Sci USA. 2006a; 103:12607–12612.
   PubMed Web of Science ®Google Scholar
• Riobo NA, Lu K, Ai X, Haines GM, Emerson CPJr. Phosphoinositide 3-kinase and Akt are essential for Sonic Hedgehog signaling. Proc Natl Acad Sci USA. 2006b; 103:4505–4510.
   PubMed Web of Science ®Google Scholar
• Roessler E, Belloni E, Gaudenz K, Jay P, Berta P, Scherer SW, Tsui LC, Muenke M. 1996. Mutations in the human Sonic Hedgehog gene cause holoprosencephaly. Nat Genet. 14:357–360.
   PubMed Web of Science ®Google Scholar
• Rohatgi R, Milenkovic L, Scott MP. 2007. Patched1 regulates hedgehog signaling at the primary cilium. Science. 317:372–376.
   PubMed Web of Science ®Google Scholar
• Rohatgi R, Milenkovic L, Corcoran RB, Scott MP. 2009. Hedgehog signal transduction by Smoothened: Pharmacologic evidence for a 2-step activation process. Proc Natl Acad Sci USA. 106:3196–3201.
   PubMed Web of Science ®Google Scholar
• Rubin LL, de Sauvage FJ. 2006. Targeting the Hedgehog pathway in cancer. Nature Rev Drug Discov. 5:1026–1033.
   PubMed Web of Science ®Google Scholar
• Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, Fu L, Holcomb T, Stinson J, Gould SE, Coleman B, LoRusso PM, Von Hoff DD, de Sauvage FJ, Low JA. 2009. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med. 361:1173–1178.
   PubMed Web of Science ®Google Scholar
• Ruel L, Rodriguez R, Gallet A, Lavenant-Staccini L, Therond PP. 2003. Stability and association of Smoothened, Costal2 and fused with Cubitus interruptus are regulated by Hedgehog. Nature Cell Biol. 5:907–913.
   PubMed Web of Science ®Google Scholar
• Ruppert JM, Kinzler KW, Wong AJ, Bigner SH, Kao FT, Law ML, Seuanez HN, O'Brien SJ, Vogelstein B. 1988. The GLI-Kruppel family of human genes. Mol Cell Biol. 8:3104–3113.
   PubMed Web of Science ®Google Scholar
• Sanchez P, Hernandez AM, Stecca B, Kahler AJ, DeGueme AM, Barrett A, Beyna M, Datta MW, Datta S, Ruiz I Altaba A. 2004. Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci USA. 101:12561–12566.
   PubMed Web of Science ®Google Scholar
• Sasaki N, Kurisu J, Kengaku M. 2010. Sonic hedgehog signaling regulates actin cytoskeleton via Tiam1-Rac1 cascade during spine formation. Mol Cell Neurosci. 45:335–344.
   PubMed Web of Science ®Google Scholar
• Satir P, Christensen ST. 2007. Overview of structure and function of mammalian cilia. Annu Rev Physiol. 69:377–400.
   PubMed Web of Science ®Google Scholar
• Scales SJ, de Sauvage FJ. 2009. Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol Sci. 30:303–312.
   PubMed Web of Science ®Google Scholar
• Sicklick JK, Li YX, Jayaraman A, Kannangai R, Qi Y, Vivekanandan P, Ludlow JW, Owzar K, Chen W, Torbenson MS, Diehl AM. 2006. Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis. Carcinogenesis. 27:748–757.
   PubMed Web of Science ®Google Scholar
• Sims-Mourtada J, Izzo JG, Ajani J, Chao KSC. 2007. Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport. Oncogene. 26:5674–5679.
   PubMed Web of Science ®Google Scholar
• Singh RR, Kunkalla K, Qu C, Schlette E, Neelapu SS, Samaniego F, Vega F. ABCG2 is a direct transcriptional target of hedgehog signaling and involved in stroma-induced drug tolerance in diffuse large B-cell lymphoma. Oncogene advance online publication, 30 May 2011;. 2011 doi:10.1038/onc.2011.195.
   Google Scholar
• Sinha S, Chen JK. 2006. Purmorphamine activates the Hedgehog pathway by targeting Smoothened. Nature Chem Biol. 2:29–30.
   PubMed Web of Science ®Google Scholar
• Stecca B, Ruiz I Altaba A. 2010. Context-dependent regulation of the GLI code in cancer by HEDGEHOG and non-HEDGEHOG signals. J Mol Cell Biol. 2:84–95.
   PubMed Web of Science ®Google Scholar
• Stecca B, Mas C, Clement V, Zbinden M, Correa R, Piguet V, Beermann F, Ruiz I Altaba A. 2007. Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways. Proc Natl Acad Sci USA. 104:5895–5900.
   PubMed Web of Science ®Google Scholar
• Stone DM, Murone M, Luoh S, Ye W, Armanini MP, Gurney A, Phillips H, Brush J, Goddard A, de Sauvage FJ, Rosenthal A. 1999. Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli. J Cell Sci. 112:4437–4448.
   PubMed Web of Science ®Google Scholar
• Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, Scott MP, Pennica D, Goddard A, Phillips H, Noll M, Hooper JE, De Sauvage F, Rosenthal A. 1996. The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature. 384:129–134.
   PubMed Web of Science ®Google Scholar
• Strigini M, Cohen SM. 1997. A Hedgehog activity gradient contributes to AP axial patterning of the Drosophila wing. Development. 124:4697–4705.
   PubMed Web of Science ®Google Scholar
• Strutt H, Thomas C, Nakano Y, Stark D, Neave B, Taylor AM, Ingham PW. 2001. Mutations in the sterol-sensing domain of patched suggest a role for vesicular trafficking in smoothened regulation. Curr Biol. 11:608–613.
   PubMed Web of Science ®Google Scholar
• Svard J, Henricson KH, Persson-Lek M, Rozell B, Lauth M, Bergstrom A, Ericson J, Toftgard R, Teglund S. 2006. Genetic elimination of suppressor of fused reveals an essential repressor function in the mammalian hedgehog signaling pathway. Developmental Cell. 10:187–197.
   PubMed Web of Science ®Google Scholar
• Taipale J, Cooper MK, Maiti T, Beachy PA. 2002. Patched acts catalytically to suppress the activity of smoothened. Nature. 418:892–897.
   PubMed Web of Science ®Google Scholar
• Taipale J, Chen JK, Cooper MK, Wang B, Mann RK, Milenkovic L, Scott MP, Beachy PA. 2000. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature. 406:1005–1009.
   PubMed Web of Science ®Google Scholar
• Taylor MD, Liu L, Raffel C, Hui CC, Mainprize TG, Zhang X, Agatep R, Chiappa S, Gao L, Lowrance A, Hao A, Goldstein AM, Stavrou T, Scherer SW, Dura WT, Wainwright B, Squire JA, Rutka JT, Hogg D. 2002. Mutations in SUFU predispose to medulloblastoma. Nat Genet. 31:306–310.
   PubMed Web of Science ®Google Scholar
• Teglund S, Toftgard R. 2010. Hedgehog beyond medulloblastoma and basal cell carcinoma. Biochim Biophys Acta. 1805:181–208.
   PubMed Web of Science ®Google Scholar
• Teh MT, Wong ST, Neill GW, Ghali LR, Philpott MP, Quinn AG. 2002. FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Res. 62:4773–4780.
   PubMed Web of Science ®Google Scholar
• Teillet MA, Watanabe Y, Jeffs P, Duprez D, Lapointe F, Le Douarin NM. 1998. Sonic hedgehog is required for survival of both myogenic and chondrogenic somitic lineages. Development. 125:2019–2030.
   PubMed Web of Science ®Google Scholar
• Tempe D, Casas M, Karaz S, Blanchet-Tournier M-F, Concordet J-P. 2006. Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP. Mol Cell Biol. 26:4316–4326.
   PubMed Web of Science ®Google Scholar
• Thayer SP, Di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, Qi YP, Gysin S, Fernandez-del Castillo C, Yajnik V, Antoniu B, McMahon M, Warshaw AL, Hebrok M. 2003. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 425:851–856.
   PubMed Web of Science ®Google Scholar
• Thibert C, Teillet M-A, Lapointe F, Mazelin L, Le Douarin NM, Mehlen P. 2003. Inhibition of neuroepithelial patched-induced apoptosis by sonic hedgehog. Science. 301:843–846.
   PubMed Web of Science ®Google Scholar
• Tian H, Callahan CA, Dupree KJ, Darbonne WC, Ahn CP, Scales SJ, De Sauvage FJ. 2009. Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc Natl Acad Sci USA. 106:4254–4259.
   PubMed Web of Science ®Google Scholar
• Tremblay MR, Nesler M, Weatherhead R, Castro AC. 2009. Recent patents for Hedgehog pathway inhibitors for the treatment of malignancy. Expert Opin Ther Pat. 19:1039–1056.
   PubMed Web of Science ®Google Scholar
• Tseng TT, Gratwick KS, Kollman J, Park D, Nies DH, Goffeau A, Saier MHJr. 1999. The RND permease superfamily: An ancient, ubiquitous and diverse family that includes human disease and development proteins. J Mol Microbiol Biotechnol. 1:107–125.
   PubMedGoogle Scholar
• 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.
   Google Scholar
• Unden AB, Holmberg E, Lundh-Rozell B, Stahle-Backdahl M, Zaphiropoulos PG, Toftgard R, Voechovsky I. 1996. Mutations in the human homologue of Drosophila patched (PTCH) in basal cell carcinomas and the Gorlin syndrome: Different in vivo mechanisms of PTCH inactivation. Cancer Res. 56:4562–4565.
   PubMed Web of Science ®Google Scholar
• Van den Heuvel M, Ingham PW. 1996. Smoothened encodes a receptor-like serpentine protein required for hedgehog signalling. Nature. 382:547–551.
   PubMedGoogle Scholar
• Varjosalo M, Taipale J. 2008. Hedgehog: functions and mechanisms. Genes Dev. 22:2454–2472.
   PubMed Web of Science ®Google Scholar
• Varjosalo M, Li S-P, Taipale J. 2006. Divergence of hedgehog signal transduction mechanism between Drosophila and mammals. Dev Cell. 10:177–186.
   PubMed Web of Science ®Google Scholar
• Varnat F, Siegl-Cachedenier I, Malerba M, Gervaz P, Ruiz I, Altaba A. 2010. Loss of WNT-TCF addiction and enhancement of HH-GLI1 signalling define the metastatic transition of human colon carcinomas. EMBO Mol Med. 2:440–457.
   Google Scholar
• Varnat F, Duquet A, Malerba M, Zbinden M, Mas C, Gervaz P, Ruiz I Altaba A. 2009. Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med. 1:338–351.
   PubMed Web of Science ®Google Scholar
• Vokes SA, Ji H, McCuine S, Tenzen T, Giles S, Zhong S, Longabaugh WJR, Davidson EH, Wong WH, McMahon AP. 2007. Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning. Development. 134:1977–1989.
   PubMed Web of Science ®Google Scholar
• Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JCJr, de Sauvage FJ, Low JA. 2009. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 361:1164–1172.
   PubMed Web of Science ®Google Scholar
• Wang B, Fallon JF, Beachy PA. 2000. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell. 100:423–434.
   PubMed Web of Science ®Google Scholar
• Wang X, Venugopal C, Manoranjan B, McFarlane N, O'Farrell E, Nolte S, Gunnarsson T, Hollenberg R, Kwiecien J, Northcott P, Taylor MD, Hawkins C, Singh SK. Sonic hedgehog regulates Bmi1 in human medulloblastoma brain tumor-initiating cells. Oncogene advance online publication, 20 June 2011;. 2011 doi:10.1038/onc.2011.232.
   Google Scholar
• Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB. 2003. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature. 422:313–317.
   PubMed Web of Science ®Google Scholar
• Wilson CW, Chen MH, Chuang PT. 2009. Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium. PLoS ONE. 4:e5182.
   PubMed Web of Science ®Google Scholar
• Xie J, Aszterbaum M, Zhang X, Bonifas JM, Zachary C, Epstein E, McCormick F. 2001. A role of PDGFRŒ ± in basal cell carcinoma proliferation. Proc Natl Acad Sci USA. 98:9255–9259.
   PubMed Web of Science ®Google Scholar
• Yam PT, Langlois SD, Morin S, Charron F. 2009. Sonic hedgehog guides axons through a noncanonical, Src-family-kinase-dependent signaling pathway. Neuron. 62:349–362.
   PubMed Web of Science ®Google Scholar
• Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, Ahn CP, Marshall D, Fu L, Januario T, Kallop D, Nannini-Pepe M, Kotkow K, Marsters JC, Rubin LL, de Sauvage FJ. 2008. A paracrine requirement for hedgehog signalling in cancer. Nature. 455:406–410.
   PubMed Web of Science ®Google Scholar
• Yauch RL, Dijkgraaf GJP, 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. 326:572–574.
   PubMed Web of Science ®Google Scholar
• Yavari A, Nagaraj R, Owusu-Ansah E, Folick A, Ngo K, Hillman T, Call G, Rohatgi R, Scott MP, Banerjee U. 2010. Role of lipid metabolism in Smoothened derepression in Hedgehog signaling. Dev Cell. 19:54–65.
   PubMed Web of Science ®Google Scholar
• Yue S, Chen Y, Cheng SY. 2009. Hedgehog signaling promotes the degradation of tumor suppressor Sufu through the ubiquitin-proteasome pathway. Oncogene. 28:492–499.
   PubMed Web of Science ®Google Scholar
• 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.
   Google Scholar
• Zhao C, Chen A, Jamieson CH, Fereshteh M, Abrahamsson A, Blum J, Kwon HY, Kim J, Chute JP, Rizzieri D, Munchhof M, VanArsdale T, Beachy PA, Reya T. 2009. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature. 458:776–779 [Erratum appears in Nature. 2009 Jul 30;460(7255):652].
   PubMed Web of Science ®Google Scholar