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The contribution of epidermal stem cells to skin cancer

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Abstract

Tumors arising from the skin are of multiple phenotypes, with differing degrees of malignant potential. In mouse models of skin carcinogenesis, tumors of squamous phenotype are the most common; however, human disease indicates that multiple phenotypes may arise from a common pool of stem cells that are then influenced by epigenetic factors. The use of transgenic and knockout gene technologies with mice is unraveling some of the specific genes regulating fate determination in stem cells other than squamous lineage, including basal cell carcinoma and sebaceous adenomas. The following review examines the evidence for the stem cell origin of epidermal tumors and the contribution of some specific gene families toward stem cell fate decisions during epidermal tumor progression.

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References

  1. Morris RJ, Potten CS. J Invest Dermatol 1999;112:470–475.

    Article  PubMed  CAS  Google Scholar 

  2. Oshima H, Rochat A, Kedzia C, Kobayashi K, Barrandon Y. Cell 2001;104:233–245.

    Article  PubMed  CAS  Google Scholar 

  3. Taylor G, Lehrer MS, Jensen PJ, Sun TT, Lavker RM. Cell 2000;102:451–461.

    Article  PubMed  CAS  Google Scholar 

  4. Watt FM. Trends Mol Med 2004;10:577–580.

    Article  PubMed  CAS  Google Scholar 

  5. Cotsarelis G, Sun T, Lavker R. Cell 1990;61:1329–1337.

    Article  PubMed  CAS  Google Scholar 

  6. Blanpain C, Lowry WE, Geoghegan A, Polak L, Fuchs E. Cell 2004;118:635–648.

    Article  PubMed  CAS  Google Scholar 

  7. Jones PH, Watt FM. Cell 1993;73:713–724.

    Article  PubMed  CAS  Google Scholar 

  8. Mackenzie IC, Bickenbach JR. Cell Tissue Res 1985;242:551–556.

    Article  PubMed  CAS  Google Scholar 

  9. Tani H, Morris RJ, Kaur P. Proc Natl Acad Sci USA 2000;97:10960–10965.

    Article  PubMed  CAS  Google Scholar 

  10. Ghazizadeh S, Taichman LB. EMBO J 2001;20:1215–1222.

    Article  PubMed  CAS  Google Scholar 

  11. Liu Y, Lyle S, Yang Z, Cotsarelis G. J Invest Dermatol 2003;121:963–968.

    Article  PubMed  CAS  Google Scholar 

  12. Bickenbach JR, Grinnell KL. Differentiation 2004;72:371–380.

    Article  PubMed  Google Scholar 

  13. Iannaccone PM, Weinberg WC, Deamant FD. Int J Cancer 1987;39:778–784.

    Article  PubMed  CAS  Google Scholar 

  14. Weinberg WC, Morgan DL, George C, Yuspa SH. Carcinogenesis 1991;12:1119–1124.

    Article  PubMed  CAS  Google Scholar 

  15. Deamant FD, Iannaccone PM. J Cell Sci 1987;88:305–312.

    PubMed  Google Scholar 

  16. Iannaccone PM, Gardner RL, Harris H. J Cell Sci 1978;29:249–269.

    PubMed  CAS  Google Scholar 

  17. Reddy AL, Fialkow PJ. Nature 1983;304:69–71.

    Article  PubMed  CAS  Google Scholar 

  18. Taguchi T, Yokoyama M, Kitamura Y. Cancer Res 1984;44:3779–3782.

    PubMed  CAS  Google Scholar 

  19. Burnham DK, Gahring LC, Daynes RA. J Natl Cancer Inst 1986;76:151–158.

    PubMed  CAS  Google Scholar 

  20. Kanjilal S, Pierceall WE, Cummings KK, Kripke ML, Ananthaswamy HN. Cancer Res 1993;53:2961–2964.

    PubMed  CAS  Google Scholar 

  21. Ren ZP, Hedrum A, Ponten F, et al. Oncogene 1996;12:765–773.

    PubMed  CAS  Google Scholar 

  22. Ren ZP, Ahmadian A, Ponten F, et al. Am J Pathol 1997;150:1791–1803.

    PubMed  CAS  Google Scholar 

  23. Yuspa SH, Dlugosz AA, Cheng CK, et al. J Invest Dermatol 1994;103:S90-S95.

    Article  Google Scholar 

  24. Bailleul B, Surani MA, White S, et al. Cell 1990;62:697–708.

    Article  PubMed  CAS  Google Scholar 

  25. Greenhalgh DA, Rothnagel JA, Quintanilla MI, et al. Mol Carcinog 1993;7:99–110.

    Article  PubMed  CAS  Google Scholar 

  26. Frame S, Balmain A. Br J Cancer 1999;80:28–33.

    PubMed  CAS  Google Scholar 

  27. Brown K, Strathdee D, Bryson S, Lambie W, Balmain A. Curr Biol 1998;8:516–524.

    Article  PubMed  CAS  Google Scholar 

  28. Binder RL, Gallagher PM, Johnson GR, et al. Mol Carcinog 1997;20:151–158.

    Article  PubMed  CAS  Google Scholar 

  29. Hansen LA, Tennant RW. Proc Natl Acad Sci USA 1994;91:7822–7826.

    Article  PubMed  CAS  Google Scholar 

  30. Morris RJ, Tryson KA, Wu KQ. Cancer Res 2000;60:226–229.

    PubMed  CAS  Google Scholar 

  31. Morris RJ, Fischer SM, Slaga TJ. Cancer Res 1986;46:3061–3066.

    PubMed  CAS  Google Scholar 

  32. Morris RJ, Coulter K, Tryson K, Steinberg SR. Cancer Res 1997;57:3436–3443.

    PubMed  CAS  Google Scholar 

  33. Morris RJ, Tacker KC, Fischer SM, Slaga TJ. Cancer Res 1988;48:6285–6290.

    PubMed  CAS  Google Scholar 

  34. Miller SJ, Wei ZG, Wilson C, Dzubow L, Sun TT, Lavker RM. J Invest Dermatol 1993;101:591–594.

    Article  PubMed  CAS  Google Scholar 

  35. Lyle S, Christofidou-Solomidou M, Liu Y, Elder DE, Albelda S, Cotsarelis G. J Cell Sci 1998;111:3179–3188.

    PubMed  CAS  Google Scholar 

  36. McGowan KM, Coulombe PA. J Cell Biol 1998;143:469–486.

    Article  PubMed  CAS  Google Scholar 

  37. Michel M, Torok N, Godbout MJ, et al. J Cell Sci 1996;109:1017–1028.

    PubMed  CAS  Google Scholar 

  38. Trempus CS, Morris RJ, Bortner CD, et al. J Invest Dermatol 2003;120:501–511.

    Article  PubMed  CAS  Google Scholar 

  39. Liang L, Bickenbach JR. Stem Cells 2002;20:21–31.

    Article  PubMed  Google Scholar 

  40. Zhou JX, Jia LW, Yang YJ, Peng S, Cao YJ, Duan EK. Cell Biol Int 2004;28:523–529.

    Article  PubMed  CAS  Google Scholar 

  41. Triel C, Vestergaard ME, Bolund L, Jensen TG, Jensen VB. Exp Cell Res 2004;295:79–90.

    Article  PubMed  CAS  Google Scholar 

  42. Terunuma A, Jackson KL, Kapoor V, Telford WG, Vogel JC. J Invest Dermatol 2003;121:1095–1103.

    Article  PubMed  CAS  Google Scholar 

  43. Morris RJ, Liu Y, Marles L, et al. Nat Biotechnol 2004;22:411–417.

    Article  PubMed  CAS  Google Scholar 

  44. Diamond I, Owolabi T, Marco M, Lam C, Glick A. J Invest Dermatol 2000;115:788–794.

    Article  PubMed  CAS  Google Scholar 

  45. Tumbar T, Guasch G, Greco V, et al. Science 2004;303:359–363.

    Article  PubMed  CAS  Google Scholar 

  46. Reya T, Clevers H. Nature 2005;434:843–850.

    Article  PubMed  CAS  Google Scholar 

  47. Rossen K, Dahlstrom KK, Mercurio AM, Wewer UM. Acta Derm Venereol 1994;74:101–105.

    PubMed  CAS  Google Scholar 

  48. Savoia P, Cremona O, Trusolino L, Pepino E, Marchisio PC. Pathol Res Pract 1994;190:950–954.

    PubMed  CAS  Google Scholar 

  49. Tennenbaum T, Weiner AK, Belanger AJ, Glick AB, Hennings H, Yuspa SH. Cancer Res 1993;53:4803–4810.

    PubMed  CAS  Google Scholar 

  50. Tuominen H, Junttila T, Karvonen J, Kallioinen M. J Cutan Pathol 1994;21:500–506.

    Article  PubMed  CAS  Google Scholar 

  51. Raghavan S, Bauer C, Mundschau G, Li Q, Fuchs E. J Cell Biol 2000;150:1149–1160.

    Article  PubMed  CAS  Google Scholar 

  52. Brakebusch C, Grose R, Quondamatteo F, et al. EMBO J 2000;19:3990–4003.

    Article  PubMed  CAS  Google Scholar 

  53. Chiang C, Swan RZ, Grachtchouk M, et al. Dev Biol 1999;205:1–9.

    Article  PubMed  CAS  Google Scholar 

  54. Mainiero F, Murgia C, Wary KK, et al. EMBO J 1997;16:2365–2375.

    Article  PubMed  CAS  Google Scholar 

  55. Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. Cell 2001;105:533–545.

    Article  PubMed  CAS  Google Scholar 

  56. Gat U, DasGupta R, Degenstein L, Fuchs E. Cell 1998;95:605–614.

    Article  PubMed  CAS  Google Scholar 

  57. Lo Celso C, Prowse DM, Watt FM. Development 2004;131:1787–1799.

    Article  PubMed  Google Scholar 

  58. Chan EF, Gat U, McNiff JM, Fuchs E. Nat Genet 1999;21:410–413.

    Article  PubMed  CAS  Google Scholar 

  59. Bale AE, Yu KP. Hum Mol Genet 2001;10:757–762.

    Article  PubMed  CAS  Google Scholar 

  60. Ghali L, Wong ST, Green J, Tidman N, Quinn AG. J Invest Dermatol 1999;113:595–599.

    Article  PubMed  CAS  Google Scholar 

  61. Aszterbaum M, Epstein J, Oro A, et al. Nat Med 1999;5:1285–1291.

    Article  PubMed  CAS  Google Scholar 

  62. Hutchin ME, Kariapper MS, Grachtchouk M, et al. Genes Dev 2005;19:214–223.

    Article  PubMed  CAS  Google Scholar 

  63. Ellis T, Smyth I, Riley E, et al. Dev Biol 2003;263:203–215.

    Article  PubMed  CAS  Google Scholar 

  64. Bickenbach JR, Vormwald-Dogan V, Bachor C, Bleuel K, Schnapp G, Boukamp P. J Invest Dermatol 1998;111:1045–1052.

    Article  PubMed  CAS  Google Scholar 

  65. Ramirez RD, Wright WE, Shay JW, Taylor RS. J Invest Dermatol 1997;108:113–117.

    Article  PubMed  CAS  Google Scholar 

  66. Wu A, Ichihashi M, Ueda M. Cancer 1999;86:2038–2044.

    Article  PubMed  CAS  Google Scholar 

  67. Taylor RS, Ramirez RD, Ogoshi M, Chaffins M, Piatyszek MA, Shay JW. J Invest Dermatol 1996;106:759–765.

    Article  PubMed  CAS  Google Scholar 

  68. Chen Z, Smith KJ, Skelton HG 3rd, Barrett TL, Greenway HT Jr, Lo SC. Exp Biol Med (Maywood) 2001;226:753–757.

    CAS  Google Scholar 

  69. Dickson MA, Hahn WC, Ino Y, et al. Mol Cell Biol 2000;20:1436–1447.

    Article  PubMed  CAS  Google Scholar 

  70. Gonzalez-Suarez E, Samper E, Ramirez A, et al. EMBO J 2001;20:2619–2630.

    Article  PubMed  CAS  Google Scholar 

  71. Gonzalez-Suarez E, Samper E, Flores JM, Blasco MA. Nat Genet 2000;26:114–117.

    Article  PubMed  CAS  Google Scholar 

  72. Bonifas JM, Pennypacker S, Chuang PT, et al. J Invest Dermatol 2001;116:739–742.

    Article  PubMed  CAS  Google Scholar 

  73. Pelisson I, Soler C, Chardonnet Y, Euvrard S, Schmitt D. Cancer Detect Prev 1996;20:20–30.

    PubMed  CAS  Google Scholar 

  74. Rounbehler RJ, Schneider-Broussard R, Conti CJ, Johnson DG. Oncogene 2001;20:5341–5349.

    Article  PubMed  CAS  Google Scholar 

  75. Arnold I, Watt FM. Curr Biol 2001;11:558–568.

    Article  PubMed  CAS  Google Scholar 

  76. Waikel RL, Kawachi Y, Waikel PA, Wang XJ, Roop DR. Nat Genet 2001;28:165–168.

    Article  PubMed  CAS  Google Scholar 

  77. Pelengaris S, Littlewood T, Khan M, Elia G, Evan G. Mol Cell 1999;3:565–577.

    Article  PubMed  CAS  Google Scholar 

  78. Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A. Nature 1999;398:708–713.

    Article  PubMed  CAS  Google Scholar 

  79. Yang A, Schweitzer R, Sun D, et al. Nature 1999;398:714–718.

    Article  PubMed  CAS  Google Scholar 

  80. Yang A, Kaghad M, Wang Y, et al. Mol Cell 1998;2:305–316.

    Article  PubMed  CAS  Google Scholar 

  81. Parsa R, Yang A, McKeon F, Green H. J Invest Dermatol 1999;113:1099–1105.

    Article  PubMed  CAS  Google Scholar 

  82. Pellegrini G, Dellambra E, Golisano O, et al. Proc Natl Acad Sci USA 2001;98:3156–3161.

    Article  PubMed  CAS  Google Scholar 

  83. Honeycutt KA, Roop DR. J Dermatol 2004;31:368–375.

    PubMed  CAS  Google Scholar 

  84. Niemann C, Unden AB, Lyle S, Zouboulis ChC, Toftgard R, Watt FM. Proc Natl Acad Sci USA 2003;100:11873–11880.

    Article  PubMed  CAS  Google Scholar 

  85. Adolphe C, Narang M, Ellis T, Wicking C, Kaur P, Wainwright B. Development 2004;131:5009–5019.

    Article  PubMed  CAS  Google Scholar 

  86. Allen M, Grachtchouk M, Sheng H, et al. Am J Pathol 2003;163:2173–2178.

    PubMed  CAS  Google Scholar 

  87. Cui CY, Durmowicz M, Ottolenghi C, et al. Hum Mol Genet 2003;12:2931–2940.

    Article  PubMed  CAS  Google Scholar 

  88. Newton K, French DM, Yan M, Frantz GD, Dixit VM. Mol Cell Biol 2004;24:1608–1613.

    Article  PubMed  CAS  Google Scholar 

  89. Muller-Decker K, Neufang G, Berger I, Neumann M, Marks F, Furstenberger G. Proc Natl Acad Sci USA 2002;99:12483–12488.

    Article  PubMed  CAS  Google Scholar 

  90. Niemann C, Owens DM, Hulsken J, Birchmeier W, Watt FM. Development 2002;129:95–109.

    PubMed  CAS  Google Scholar 

  91. Nakamura Y, Fukami K, Yu H, et al. EMBO J 2003;22:2981–2991.

    Article  PubMed  CAS  Google Scholar 

  92. Fong LY, Fidanza V, Zanesi N, et al. Proc Natl Acad Sci USA 2000;97:4742–4747.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Stuart H. Yuspa.

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Gerdes, M.J., Yuspa, S.H. The contribution of epidermal stem cells to skin cancer. Stem Cell Rev 1, 225–231 (2005). https://doi.org/10.1385/SCR:1:3:225

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