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The hedgehog signalling pathway in tumorigenesis and development

Oncogene volume 18, pages 7844–7851 (1999)Cite this article

Abstract

The hedgehog signalling pathway is responsible for the embryonic patterning of a range of tissues, and it is now known that dysregulation of this pathway can result in the formation of several tumour types. This cascade is regulated at the cell surface by the opposing actions of the patched and smoothened molecules which together form a receptor complex for hedgehog. The discovery that inactivation of the human patched gene is responsible for familial and sporadic forms of basal cell carcinoma firmly established a role for dysregulation of hedgehog signalling in tumorigenesis. Other key members of this pathway have also been shown to be involved in tumour formation, as have more distal downstream targets of hedgehog signalling. Since it appears that tumorigenesis results from constitutive activation of hedgehog responsive genes, the identification of novel downstream targets of hedgehog signalling in given cell types is likely to increase our understanding of the molecular processes underlying tumour formation.

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References

  • Alcedo J, Ayzenzon M, Von Ohlen T, Noll M and Hooper JE. . 1996 Cell 86: 221–232.

  • Altaba AR. . 1999 Development 126: 3205–3216.

  • Aszterbaum M, Epstein JH, Oro AE, Goodrich LV, Scott MP and Epstein Jr EH. . 1998a Am. J. Hum. Genet. 63: A39.

  • Aszterbaum M, Rothman A, Johnson RL, Fisher M, Xie J, Bonifas JM, Zhang X, Scott MP and Epstein Jr EH. . 1998b J. Invest. Dermatol. 110: 885–888.

  • Aza-Blanc P, Ramirez-Weber FA, Laget MP, Schwartz C and Kornberg TB. . 1997 Cell 89: 1043–1053.

  • Basler K and Struhl G. . 1994 Nature 368: 208–214.

  • Bellusci S, Furuta Y, Rush MG, Henderson R, Winnier G and Hogan BL. . 1997 Development 124: 53–63.

  • Bitgood MJ and McMahon AP. . 1995 Dev. Biol. 172: 126–138.

  • Bitgood MJ, Shen L and McMahon AP. . 1996 Curr. Biol. 6: 298–304.

  • Bodak N, Queille S, Avril MF, Bouadjar B, Drougard C, Sarasin A and Daya-Grosjean L. . 1999 Proc. Natl. Acad. Sci. USA 96: 5117–5122.

  • Byrne C, Tainsky M and Fuchs E. . 1994 Development 120: 2369–2383.

  • Carpenter D, Stone DM, Brush J, Ryan A, Armanini M, Frantz G, Rosenthal A and de Sauvage FJ. . 1998 Proc. Natl. Acad. Sci. USA 95: 13630–13634.

  • Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, Gu J, Pavan WJ, Krizman DB, Nagle J, Polymeropoulos MH, Sturley SL, Ioannou YA, Higgins ME, Comly M, Cooney A, Brown A, Kaneski CR, Blanchettemackie EJ, Dwyer NK, Neufeld EB, Chang TY, Liscum L, Strauss JF and Pentchev PG. . 1997 Science 277: 228–231.

  • Chen C-H, von Kessler DP, Park W, Wang B, Ma Y and Beachy PA. . 1999 Cell 98: 305–316.

  • Chaung PT and McMahon AP. . 1999 Nature 397: 617–621.

  • Cooper MK, Porter JA, Young KE and Beachy PA. . 1998 Science 280: 1603–1607.

  • Dahmane N, Lee J, Robins P, Heller P and Altaba AR. . 1997 Nature 389: 876–881.

  • Dai P, Akimaru H, Tanaka Y, Maekawa T, Nakafuku M and Ishii S. . 1999 J. Biol. Chem. 274: 8143–8152.

  • Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA and McMahon AP. . 1993 Cell 75: 1417–1430.

  • Fah H, Oro AE, Scott MP and Khavari PA. . 1997 Nat. Med. 3: 788–792.

  • Gailani M, Stahle-Backdahl M, Leffell D, Glynn M, Zaphiropolous P, Pressman C, Unden AB, Dean M, Brach DE, Bale AE and Toftgard R. . 1996 Nat. Genet. 14: 78–81.

  • Gailani MR, Bale SJ, Leffell DJ, DiGiovanna JJ, Peck GL, Poliak S, Drum MA, Passtakia B, McBride OW, Kase R, Greene M, Mulvihill JJ and Bale AE. . 1992 Cell 69: 111–117.

  • Goodrich LV, Johnson RJ, Milenkovic L, McMahon JA and Scott MP. . 1996 Genes Dev. 10: 301–312.

  • Goodrich LV, Milenkovic L, Higgins KM and Scott MP. . 1997 Science 277: 1109–1113.

  • Goodrich LV, Jung D, Higgins KM, Scott MP. . 1999 Dev. Biol. 211: 323–334.

  • Gorlin RJ. . 1995 Dermatol. Clin. 13: 113–125.

  • Hahn H, Christiansen J, Wicking C, Zaphiropoulos PG, Chidambaram A, Gerrard B, Vorechovsky I, Bale AE, Toftgard R, Dean M and Wainwright B. . 1996a J. Biol. Chem. 271: 12125–12128.

  • Hahn H, Wicking C, Zaphiropoulos 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 and Bale AE. . 1996b Cell 85: 841–851.

  • Hahn H, Wojnowski L, Zimmer AM, Hall J, Miller G and Zimmer A. . 1998 Nat. Med. 4: 619–622.

  • Hardcastle Z, Mo R, Hui C-C and Sharpe PT. . 1998 Development 125: 2803–2811.

  • Hilton DJ, Richardson RT, Alexander WS, Viney EM, Willson TA, Sprigg NS, Starr R, Nicholson SE, Metcalf D and Nicola NA. . 1998 Proc. Natl. Acad. Sci. USA 95: 114–119.

  • Ingham PW. . 1998 EMBO J. 17: 3505–11.

  • Johnson RL, Rothman AI, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein Jr EH and Scott MP. . 1996 Science 272: 1668–1671.

  • Kang S, Graham JM, Olney AH and Biesecker LG. . 1997 Nature Genet. 15: 266–268.

  • Kinzler KW, Ruppert JM, Bigner SH and Vogelstein B. . 1988 Nature 332: 371–374.

  • Kinzler KW and Vogelstein B. . 1996 Cell 87: 159–170.

  • Kogerman P, Grimm T, Kogerman L, Krause D, Unden AB, Sandstedt B, Toftgard R and Zaphiropoulos P. . 1999 Nat. Cell Biol. 1: 312–319.

  • Lam CW, Xie J, To KF, Ng HK, Lee KC, Yuen NW, Lim PL, Chan LY, Tong SF and McCormick F. . 1999 Oncogene 18: 833–836.

  • Lee JJ, Ekker SC, von Kessler DP, Porter JA, Sub BI and Beachy PA. . 1994 Science 266: 1528–1537.

  • Lee JJ, von Kessler DP, Parks S and Beachy PA. . 1992 Cell 71: 33–50.

  • Litingung Y, Lei L, Westphal H and Chiang C. . 1998 Nature Genet. 20: 58–61.

  • Loftus SK, Morris JA, Carstea ED, Gu JZ, Cummings C, Brown A, Ellison J, Ohno K, Rosenfeld MA, Tagle DA, Pentchev PG and Pavan WJ. . 1997 Science 277: 232–235.

  • Maesawa C, Tamura G, Iwaya T, Ogasawara S, Ishida K, Sato N, Nishizuka S, Suzuki Y, Ikeda K, Aoki K, Saito K and Satodate R. . 1998 Genes Chrom. Cancer 21: 276–279.

  • Marigo V, Davey RA, Zuo Y, Cunningham JM and Tabin CJ. . 1996 Nature 384: 176–179.

  • Marigo V and Tabin CJ. . 1996 Proc. Natl. Acad. Sci. USA 93: 9346–9351.

  • Markey AC, Lane EB, Macdonald DM and Leigh IM. . 1992 Br. J. Dermatol. 126: 154–160.

  • McGarvey TW, Maruta Y, Tomaszewski JE, Linnenbach AJ and Malkowicz SB. . 1998 Oncogene 17: 1167–1172.

  • Monnier V, Dussillol F, Alves G, Lamour-Isnard C and Plessis A. . 1998 Curr. Biol. 8: 583–586.

  • Motoyama J, Heng H, Crackower MA, Takabatake T, Takeshima K, Tsui LC and Hui C-C. . 1998 Mech. Dev. 78: 81–84.

  • Murone M, Rosenthal A and de Sauvage FJ. . 1999 Curr. Biol. 9: 76–84.

  • Nakjang Y and Kullavanijaya P. . 1994 J. Dermatol. 21: 660–663.

  • Nusse R, Theunissen H, Wagenaar E, Rijsewijk F, Gennissen A, Otte A, Schuuring E and van Ooyen A. . 1990 Mol. Cell. Biol. 10: 4170–4179.

  • Nusslein-Volhard C and Wieschaus E. . 1980 Nature 287: 795–801.

  • Ohlmeyer JT and Kalderon D. . 1998 Nature 396: 749–753.

  • Orenic TV, Slusarski DC, Kroll KL and Holmgren RA. . 1990 Genes Dev. 4: 1053–1067.

  • Oro AE, Higgins KM, Hu Z, Bonifas JM, Epstein Jr EH and Scott MP. . 1997 Science 276: 817–821.

  • Pietsch T, Waha A, Koch A, Kraus J, Albrecht S, Tonn J, Sorenson N, Berthold F, Henk B, Wolk HK, von Deimling A, Wainwright B, Chenevix-Trench G, Weistler OD and Wicking CA. . 1997 Cancer Res. 57: 2085–2088.

  • Porter JA, von Kessler DP, Ekker SC, Young KE, Lee JJ, Moses K and Beachy PA. . 1995 Nature 374: 363–366.

  • Porter JA, Young KE and Beachy PA. . 1996 Science 274: 255–259.

  • Preat T, Therond P, Lamour-Isnard C, Limbourg-Bouchon B, Tricoire H, Erk I, Mariol MC and Busson D. . 1990 Nature 347: 87–89.

  • Radhakrishna U, Wild A, Grzeschik K-H and Antonarakis SE. . 1997 Nature Genet. 17: 269–271.

  • Raffel C, Jenkins RB, Frederick L, Hebrink D, Alderete B, Fults DW and James CD. . 1997 Cancer Res. 67: 842–845.

  • Reifenberger J, Wolter M, Weber RG, Megahed M, Ruzicka T, Lichter P and Reifenberger G. . 1998 Cancer Res. 58: 1798–1803.

  • Riddle RD, Johnson RL, Laufer E and Tabin C. . 1993 Cell 75: 1401–1416.

  • Rodriguez I and Basler K. . 1997 Nature 389: 614–618.

  • Roelink H, Porter JA, Chiang C, Tanabe Y, Chang DT, Beachy PA and Jessell TM. . 1995 Cell 81: 445–455.

  • Roessler E, Belloni E, Gaudenz K, Jay P, Berta P, Scherer SW, Tsui L-C and Muenke M. . 1996 Nature Genet. 14: 357–360.

  • Sasaki H, Nishizaki Y, Hui C-C, Nakafuku M and Kondoh H. . 1999 Development 126: 3915–3924.

  • Scotto J, Fears T, Kraemer KH and Fraumeni JJ. . (1996) Cancer Epidemiology and Prevention. Schottenfeld D and Fraumeni, JF (eds). Oxford University Press: Oxford pp. 1313–1330.

    Google Scholar 

  • Shanley S, Ratcliffe J, Hockey A, Haan E, Oley C, Ravine D, Martin N, Wicking C and Chenevix-Trench G. . 1994 Am. J. Med. Genet. 50: 282–290.

  • Sidransky D. . 1996 Nat. Genet. 14: 7–8.

  • Sisson JC, Ho KS, Suyama K and Scott MP. . 1997 Cell 90: 235–245.

  • Smyth I, Narang MA, Evans T, Heimann C, Nakamura Y, Chenevix-Trench G, Pietsch T, Wicking C and Wainwright BJ. . 1999 Hum. Mol. Genet. 8: 291–297.

  • St-Jacques B, Dassule HR, Karavanova I, Botchkarev VA, Li J, Danielian PS, McMahon JA, Lewis PM, Paus R and McMahon AP. . 1998 Curr. Biol. 8: 1058–1068.

  • Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, Scott MP, Pennica D, Goddard A, Philips H, Noll M, Hooper JE, de Sauvage D and Rosenthal A. . 1996 Nature 384: 129–134.

  • Takabatake T, Ogawa M, Takahashi TC, Mizuno M, Okamoto M and Takeshima K. . 1997 FEBS Lett. 410: 485–489.

  • Tay CH and Seah CS. . 1975 Med. J. Aust. 2: 424–428.

  • Unden AB, Zaphiropoulos PG, Bruce K, Toftgard R and Stahle-Backdahl M. . 1997 Cancer Res. 57: 2336–2340.

  • van den Heuvel M and Ingham PW. . 1996 Nature 382: 547–551.

  • Vasiliauskas D, Hancock S and Stern CD. . 1999 Mech. Dev. 82: 79–94.

  • Van Ohlen T, Lessing D, Nusse R and Hooper JE. . 1997 Proc. Natl. Acad. Sci. USA 94: 2404–2409.

  • Vorechovsky I, Tingby O, Hartman M, Stromberg B, Nister M, Collins VP and Toftgard R. . 1997a Oncogene 15: 361–366.

  • Vorechovsky I, Unden AB, Sandstedt B, Toftgard R and StahlBackdahl M. . 1997b Cancer Res. 57: 4677–4681.

  • Vortkamp A, Gessler M and Grzeschik K-H. . 1991 Nature 352: 539–540.

  • Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM and Tabin CJ. . 1996 Science 273: 613–622.

  • Weedon D. . (1991) Malignant Skin Tumours. Emmett J and O'Rourke M (eds). Churchill Livingstone: New York pp. 109–127.

    Google Scholar 

  • Wicking C, Evans T, Henk B, Hayward N, Simms LA, Chenevix-Trench G, Pietsch T and Wainwright B. . 1998 Oncogene 16: 1091–1093.

  • Wicking C, Shanley S, Smyth I, Gillies S, Negus K, Graham S, Suthers G, Haites N, Edwards M, Wainwright B and Chenevix-Trench G. . 1997 Am. J. Hum Genet. 60: 21–26.

  • Wolter M, Reifenberger J, Sommer C, Ruzicka T and Reifenberger G. . 1997 Cancer Res. 57: 2581–2585.

  • Wong SS, Tan KC and Goh CL. . 1998 J. Am. Acad. Dermatol. 38: 179–185.

  • Xie J, Murone M, Luoh S-M, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam C-W, Hynes M, Goddard A, Rosenthal A, Epstein Jr EH and de Sauvage FJ. . 1998 Nature 391: 90–92.

  • Yeh S. . 1973 Hum. Pathol. 4: 469–485.

  • Zeigler A, Leffell DJ, Kunala S, Sharma HW, Gailani M, Halperin AJ, Baden HP, Shapiro PE, Bale AE and Brash DE. . 1993 Proc. Natl. Acad. Sci. USA 90: 4216–4220.

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  1. Centre for Molecular and Cellular Biology, University of Queensland, St Lucia 4072, Queensland, Australia

    Carol Wicking & Ian Smyth

  2. Department of Genetics, Yale University School of Medicine, New Haven, 06520, Connecticut, CT, USA

    Allen Bale

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Wicking, C., Smyth, I. & Bale, A. The hedgehog signalling pathway in tumorigenesis and development. Oncogene 18, 7844–7851 (1999). https://doi.org/10.1038/sj.onc.1203282

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