From keratinocyte to cancer: The pathogenesis and modeling of cutaneous squamous cell carcinoma

Journal of Clinical Investigation

Volumn 122, Issue 2, 2012, Pages 464-472

  Ratushny, Vladimir ^a   Gober, Michael D ^a   Hick, Ryan ^a   Ridky, Todd W ^a   Seykora, John T ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (3 DIMETHYLAMINOPROPYLAMINO) 2 (4 METHOXYSTYRYL)QUINAZOLINE; AZATHIOPRINE; CYCLOSPORIN; DICLOFENAC; FLUOROURACIL; IMATINIB; IMIQUIMOD; VORICONAZOLE;

ACTINIC KERATOSIS; BASEMENT MEMBRANE; CANDIDIASIS; CARCINOGENESIS; CUTANEOUS SQUAMOUS CELL CARCINOMA; DRUG INDUCED CANCER; EXTRACELLULAR MATRIX; GASTROINTESTINAL STROMAL TUMOR; GRAFT RECIPIENT; HUMAN; INVASIVE ASPERGILLOSIS; KERATINOCYTE; MYELOID LEUKEMIA; NONHUMAN; ORGAN TRANSPLANTATION; PATHOGENESIS; PHOTOSENSITIVITY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SKIN CARCINOMA; SQUAMOUS CELL CARCINOMA; TREATMENT PLANNING; TUMOR XENOGRAFT;

ANIMALS; CARCINOMA, SQUAMOUS CELL; DISEASE PROGRESSION; EXTRACELLULAR MATRIX; HUMANS; KERATINOCYTES; KERATOSIS, ACTINIC; MUTATION; PRECANCEROUS CONDITIONS; SIGNAL TRANSDUCTION; SKIN NEOPLASMS; SUNLIGHT; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84856557238     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI57415     Document Type: Review

References (109)

1. Rogers HW, et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol. 2010;146(3):283-287.
2. Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 2000;42(1 pt 2):4-7.
3. Marks R. An overview of skin cancers. Incidence and causation. Cancer. 1995;75(2 suppl):607-612.
4. Wolff KG, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York, New York, USA: McGraw-Hill; 2007.
5. Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen use. N Engl J Med. 1993;329(16):1147-1151. (Pubitemid 23295456)
6. Mittelbronn MA, Mullins DL, Ramos-Caro FA, Flowers FP. Frequency of pre-existing actinic keratosis in cutaneous squamous cell carcinoma. Int J Dermatol. 1998;37(9):677-681. (Pubitemid 28428318)
7. Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2000;42(1 pt 2):23-24.
8. Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet. 1988;1(8589):795-797. (Pubitemid 18094914)
9. Criscione VD, Weinstock MA, Naylor MF, Luque C, Eide MJ, Bingham SF. Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer. 2009;115(11):2523-2530.
10. Stockfleth E. Actinic keratoses. Cancer Treat Res. 2009;146:227-239.
11. Cockerell CJ. Histopathology of incipient intraepidermal squamous cell carcinoma ("actinic keratosis"). J Am Acad Dermatol. 2000;42(1 pt 2):11-17.
12. Aho M, Vesterinen E, Meyer B, Purola E, Paavonen J. Natural history of vaginal intraepithelial neoplasia. Cancer. 1991;68(1):195-197.
13. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61(5):759-767.
14. Dajee M, et al. NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. Nature. 2003;421(6923):639-643. (Pubitemid 36227672)
15. Lazarov M, et al. CDK4 coexpression with Ras generates malignant human epidermal tumorigenesis. Nat Med. 2002;8(10):1105-1114. (Pubitemid 35175965)
16. Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature. 2001; 411(6835):366-374. (Pubitemid 32467046)
17. Brash DE, et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci U S A. 1991;88(22):10124-10128. (Pubitemid 21915787)
18. Jiang W, Ananthaswamy HN, Muller HK, Kripke ML. p53 protects against skin cancer induction by UV-B radiation. Oncogene. 1999;18(29):4247-4253. (Pubitemid 29377855)
19. Kubo Y, et al. p53 gene mutations in human skin cancers and precancerous lesions: comparison with immunohistochemical analysis. J Invest Dermatol. 1994;102(4):440-444.
20. Ziegler A, et al. Sunburn and p53 in the onset of skin cancer. Nature. 1994;372(6508):773-776.
21. Nelson MA, et al. Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers. Cancer Lett. 1994;85(1):23-29. (Pubitemid 24280158)
22. Ortonne JP. From actinic keratosis to squamous cell carcinoma. Br J Dermatol. 2002;146(suppl 61):20-23.
23. Nakazawa H, et al. UV and skin cancer: specific p53 gene mutation in normal skin as a biologically relevant exposure measurement. Proc Natl Acad Sci U S A. 1994;91(1):360-364. (Pubitemid 24018704)
24. Campbell C, Quinn AG, Ro YS, Angus B, Rees JL. p53 mutations are common and early events that precede tumor invasion in squamous cell neoplasia of the skin. J Invest Dermatol. 1993;100(6):746-748. (Pubitemid 23151232)
25. Baker SJ, et al. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res. 1990;50(23):7717-7722.
26. Donghi R, Longoni A, Pilotti S, Michieli P, Della Porta G, Pierotti MA. Gene p53 mutations are restricted to poorly differentiated and undifferentiated carcinomas of the thyroid gland. J Clin Invest. 1993;91(4):1753-1760. (Pubitemid 23127381)
27. Uchida T, et al. p53 mutations and prognosis in bladder tumors. J Urol. 1995;153(4):1097-1104.
28. Kolev V, et al. EGFR signalling as a negative regulator of Notch1 gene transcription and function in proliferating keratinocytes and cancer. Nat Cell Biol. 2008;10(8):902-911.
29. Zhao L, et al. Srcasm inhibits Fyn-induced cutaneous carcinogenesis with modulation of Notch1 and p53. Cancer Res. 2009;69(24):9439-9447.
30. Kim MS, et al. Increased expression of activating transcription factor 3 is related to the biologic behavior of cutaneous squamous cell carcinomas. Hum Pathol. 2011;42(7):954-959.
31. Lentini M, Schepis C, Cuppari DA, Batolo D. Tenascin expression in actinic keratosis. J Cutan Pathol. 2006;33(11):716-720. (Pubitemid 44704322)
32. Toll A, et al. MYC gene numerical aberrations in actinic keratosis and cutaneous squamous cell carcinoma. Br J Dermatol. 2009;161(5):1112-1118.
33. Toll A, et al. Epidermal growth factor receptor gene numerical aberrations are frequent events in actinic keratoses and invasive cutaneous squamous cell carcinomas. Exp Dermatol. 2010;19(2):151-153.
34. Sekulic A, et al. Loss of inositol polyphosphate 5- phosphatase is an early event in development of cutaneous squamous cell carcinoma. Cancer Prev Res (Phila). 2010;3(10):1277-1283.
35. Einspahr JG, et al. Relationship of p53 mutations to epidermal cell proliferation and apoptosis in human UV-induced skin carcinogenesis. Neoplasia. 1999;1(5):468-475.
36. Rehman I, Takata M, Wu YY, Rees JL. Genetic change in actinic keratoses. Oncogene. 1996;12(12):2483-2490. (Pubitemid 26237776)
37. Purdie KJ, et al. Allelic imbalances and microdeletions affecting the PTPRD gene in cutaneous squamous cell carcinomas detected using single nucleotide polymorphism microarray analysis. Genes Chromosomes Cancer. 2007;46(7):661-669. (Pubitemid 46802333)
38. Mortier L, et al. Progression of actinic keratosis to squamous cell carcinoma of the skin correlates with deletion of the 9p21 region encoding the p16(INK4a) tumor suppressor. Cancer Lett. 2002;176(2):205-214. (Pubitemid 34139786)
39. Pacifico A, Goldberg LH, Peris K, Chimenti S, Leone G, Ananthaswamy HN. Loss of CDKN2A and p14ARF expression occurs frequently in human nonmelanoma skin cancers. Br J Dermatol. 2008;158(2):291-297.
40. Burnworth B, et al. The multi-step process of human skin carcinogenesis: a role for p53, cyclin D1, hTERT, p16, and TSP-1. Eur J Cell Biol. 2007;86(11-12):763-780. (Pubitemid 350082194)
41. Nindl I, et al. Low prevalence of p53, p16(INK4a) and Ha-ras tumour-specific mutations in low-graded actinic keratosis. Br J Dermatol. 2007;156(suppl 3):34-39. (Pubitemid 46632509)
42. Pierceall WE, Goldberg LH, Tainsky MA, Mukhopadhyay T, Ananthaswamy HN. Ras gene mutation and amplification in human nonmelanoma skin cancers. Mol Carcinog. 1991;4(3):196-202.
43. Spencer JM, Kahn SM, Jiang W, DeLeo VA, Weinstein IB. Activated ras genes occur in human actinic keratoses, premalignant precursors to squamous cell carcinomas. Arch Dermatol. 1995;131(7):796-800.
44. Boukamp P. Non-melanoma skin cancer: what drives tumor development and progression? Carcinogenesis. 2005;26(10):1657-1667. (Pubitemid 41487981)
45. Khavari PA. Modelling cancer in human skin tissue. Nat Rev Cancer. 2006;6(4):270-280.
46. Bamford S DE, et al. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website; http://www.sanger.ac.uk/cosmic. Br J Cancer. 2004;91(2):355-358.
47. Marinkovich MP. Tumour microenvironment: laminin 332 in squamous-cell carcinoma. Nat Rev Cancer. 2007;7(5):370-380. (Pubitemid 46652480)
48. Martins VL, et al. Increased invasive behaviour in cutaneous squamous cell carcinoma with loss of basement-membrane type VII collagen. J Cell Sci. 2009;122(pt 11):1788-1799.
49. Reuter JA, et al. Modeling inducible human tissue neoplasia identifies an extracellular matrix interaction network involved in cancer progression. Cancer Cell. 2009;15(6):477-488.
50. Kamstrup MR, Gniadecki R, Skovgaard GL. Putative cancer stem cells in cutaneous malignancies. Exp Dermatol. 2007;16(4):297-301. (Pubitemid 46394844)
51. Morris RJ, Coulter K, Tryson K, Steinberg SR. Evidence that cutaneous carcinogen-initiated epithelial cells from mice are quiescent rather than actively cycling. Cancer Res. 1997;57(16):3436-3443. (Pubitemid 27355489)
52. Bailleul B, et al. Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter. Cell. 1990;62(4):697-708.
53. Brown K, Strathdee D, Bryson S, Lambie W, Balmain A. The malignant capacity of skin tumours induced by expression of a mutant H-ras transgene depends on the cell type targeted. Curr Biol. 1998;8(9):516-524. (Pubitemid 28203071)
54. Lapouge G, et al. Identifying the cellular origin of squamous skin tumors. Proc Natl Acad Sci U S A. 2011;108(18):7431-7436.
55. Brittan M, et al. Bone marrow cells engraft within the epidermis and proliferate in vivo with no evidence of cell fusion. J Pathol. 2005;205(1):1-13. (Pubitemid 40029087)
56. Li HC, Stoicov C, Rogers AB, Houghton J. Stem cells and cancer: evidence for bone marrow stem cells in epithelial cancers. World J Gastroenterol. 2006;12(3):363-371. (Pubitemid 43329251)
57. Jin H, et al. A homing mechanism for bone marrow-derived progenitor cell recruitment to the neovasculature. J Clin Invest. 2006;116(3):652-662. (Pubitemid 43326874)
58. Ridky TW, Chow JM, Wong DJ, Khavari PA. Invasive three-dimensional organotypic neoplasia from multiple normal human epithelia. Nat Med. 2010;16(12):1450-1455.
59. Zhang JY, Tao S, Kimmel R, Khavari PA. CDK4 regulation by TNFR1 and JNK is required for NF-kappaB-mediated epidermal growth control. J Cell Biol. 2005;168(4):561-566. (Pubitemid 40271021)
60. van Hogerlinden M, Rozell BL, Ahrlund-Richter L, Toftgard R. Squamous cell carcinomas and increased apoptosis in skin with inhibited Rel/nuclear factor-kappaB signaling. Cancer Res. 1999;59(14):3299-3303. (Pubitemid 29334479)
61. Yadav V, Denning MF. Fyn is induced by Ras/PI3K/Akt signaling and is required for enhanced invasion/migration. Mol Carcinog. 2011;50(5):346-352.
62. Muller B. Imatinib and its successors - how modern chemistry has changed drug development. Curr Pharm Des. 2009;15(2):120-133.
63. Ayli EE, Li W, Brown TT, Witkiewicz A, Elenitsas R, Seykora JT. Activation of Src-family tyrosine kinases in hyperproliferative epidermal disorders. J Cutan Pathol. 2008;35(3):273-277. (Pubitemid 351171253)
64. Matsumoto T, et al. Overexpression of a constitutively active form of c-src in skin epidermis increases sensitivity to tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Mol Carcinog. 2002;33(3):146-155. (Pubitemid 34195195)
65. Matsumoto T, et al. Targeted expression of c-Src in epidermal basal cells leads to enhanced skin tumor promotion, malignant progression, and metastasis. Cancer Res. 2003;63(16):4819-4828. (Pubitemid 37022612)
66. Li W, Marshall C, Mei L, Gelfand J, Seykora JT. Srcasm corrects Fyn-induced epidermal hyperplasia by kinase down-regulation. J Biol Chem. 2007;282(2):1161-1169. (Pubitemid 47076571)
67. Seykora JT, Mei L, Dotto GP, Stein PL. 'Srcasm: a novel Src activating and signaling molecule. J Biol Chem. 2002;277(4):2812-2822. (Pubitemid 34953313)
68. Li W, et al. Srcasm modulates EGF and Src-kinase signaling in keratinocytes. J Biol Chem. 2005;280(7):6036-6046. (Pubitemid 40280087)
69. Li W, Marshall C, Mei L, Gelfand J, Seykora JT. Srcasm corrects fyn-induced epidermal hyperplasia by kinase down-regulation. J Biol Chem. 2007;282(2):1161-1169. (Pubitemid 47076571)
70. Yadav V, Yanez NC, Fenton SC, Denning MF. Loss of protein kinase C delta gene expression in human squamous cell carcinomas: a laser capture microdissection study. Am J Pathol. 2010;176(3):1091-1096.
71. Denning MF, Wang Y, Nickoloff BJ, Wrone-Smith T. Protein kinase C delta is activated by capase-dependent proteolysis during ultraviolet radiation-induced apoptosis of human keratinocytes. J Biol Chem. 1998;273(45):29995-30002. (Pubitemid 28510018)
72. Joseloff E, et al. Src family kinases phosphorylate protein kinase C delta on tyrosine residues and modify the neoplastic phenotype of skin keratinocytes. J Biol Chem. 2002;277(14):12318-12323. (Pubitemid 34952802)
73. Dotto GP. Notch tumor suppressor function. Oncogene. 2008;27(38):5115- 5123.
74. Okuyama R, Tagami H, Aiba S. Notch signaling: its role in epidermal homeostasis and in the pathogenesis of skin diseases. J Dermatol Sci. 2008;49(3):187-194. (Pubitemid 351179207)
75. Okuyama R, et al. High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism. Dev Cell. 2004;6(4):551-562. (Pubitemid 38456183)
76. Lefort K, et al. Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKalpha kinases. Genes Dev. 2007;21(5):562-577. (Pubitemid 46409471)
77. Nicolas M, et al. Notch1 functions as a tumor suppressor in mouse skin. Nat Genet. 2003;33(3):416-421. (Pubitemid 36278861)
78. Kim DJ, Angel JM, Sano S, DiGiovanni J. Constitutive activation and targeted disruption of signal transducer and activator of transcription 3 (Stat3) in mouse epidermis reveal its critical role in UVB-induced skin carcinogenesis. Oncogene. 2009;28(7):950-960.
79. Scholl FA, Dumesic PA, Khavari PA. Mek1 alters epidermal growth and differentiation. Cancer Res. 2004;64(17):6035-6040. (Pubitemid 39129401)
80. Tarutani M, Cai T, Dajee M, Khavari PA. Inducible activation of Ras and Raf in adult epidermis. Cancer Res. 2003;63(2):319-323. (Pubitemid 36152487)
81. Hamad NM, et al. Distinct requirements for Ras oncogenesis in human versus mouse cells. Genes Dev. 2002;16(16):2045-2057.
82. Huarte M, et al. A large intergenic noncoding rna induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142(3):409-419.
83. Zhang L, Stokes N, Polak L, Fuchs E. Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment. Cell Stem Cell. 2011;8(3):294-308.
84. Sand M, et al. Expression levels of the microRNA processing enzymes drosha and dicer in epithelial skin cancer. Cancer Invest. 2010;28(6):649-653.
85. Dziunycz P, et al. Squamous cell carcinoma of the skin shows a distinct microRNA profile modulated by UV radiation. J Invest Dermatol. 2010;130(11):2686-2689.
86. Lou Y, Yang X, Wang F, Cui Z, Huang Y. MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein. Int J Mol Med. 2010;26(6):819-827.
87. Moriyama T, et al. MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance. Mol Cancer Ther. 2009;8(5):1067-1074.
88. Almquist LM, et al. The role of TP53 and MDM2 polymorphisms in TP53 mutagenesis and risk of non-melanoma skin cancer. Carcinogenesis. 2011;32(3):327-330.
89. Hung T, et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet. 2011;43(7):621-629.
90. Gupta RA, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071-1076.
91. Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. 2003;348(17):1681-1691. (Pubitemid 36459475)
92. Berg D, Otley CC. Skin cancer in organ transplant recipients: Epidemiology, pathogenesis, and management. J Am Acad Dermatol. 2002;47(1):1-17.
93. Hofbauer GF, Bouwes Bavinck JN, Euvrard S. Organ transplantation and skin cancer: basic problems and new perspectives. Exp Dermatol. 2010;19(6):473-482.
94. O'Donovan P, et al. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science. 2005;309(5742):1871-1874. (Pubitemid 41325100)
95. Wu X, et al. Opposing roles for calcineurin and ATF3 in squamous skin cancer. Nature. 2010;465(7296):368-372.
96. Hojo M, et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature. 1999;397(6719):530-534.
97. Cowen EW, et al. Chronic phototoxicity and aggressive squamous cell carcinoma of the skin in children and adults during treatment with voriconazole. J Am Acad Dermatol. 2010;62(1):31-37.
98. Vadnerkar A, et al. Voriconazole exposure and geographic location are independent risk factors for squamous cell carcinoma of the skin among lung transplant recipients. J Heart Lung Transplant. 2010;29(11):1240-1244.
99. Baron JM, et al. Expression of multiple cytochrome P450 enzymes and multidrug resistance-associated transport proteins in human skin keratinocytes. J Invest Dermatol. 2001;116(4):541-548. (Pubitemid 32299843)
100. Carpenter PM, et al. Nuclear morphometry and molecular biomarkers of actinic keratosis, sun-damaged, and nonexposed skin. Cancer Epidemiol Biomarkers Prev. 2004;13(12):1996-2002. (Pubitemid 40054291)
101. Talghini S, Halimi M, Baybordi H. Expression of P27, Ki67 and P53 in squamous cell carcinoma, actinic keratosis and Bowen disease. Pak J Biol Sci. 2009;12(12):929-933.
102. Weinstock MA, Lee KC, Chren MM, Marcolivio K. Quality of life in the actinic neoplasia syndrome: The VA Topical Tretinoin Chemoprevention (VATTC) Trial. J Am Acad Dermatol. 2009;61(2):207-215.
103. van der Fits L, et al. Imiquimod-induced psoriasislike skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol. 2009;182(9):5836-5845.
104. Kose O, Koc E, Erbil AH, Caliskan E, Kurumlu Z. Comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% imiquimod cream in the treatment of actinic keratosis. J Dermatolog Treat. 2008;19(3):159-163. (Pubitemid 351882995)
105. Tang X, et al. CP-31398 restores mutant p53 tumor suppressor function and inhibits UVB-induced skin carcinogenesis in mice. J Clin Invest. 2007;117(12):3753-3764. (Pubitemid 350224086)
106. Druker BJ, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001;344(14):1038-1042. (Pubitemid 32267973)
107. Druker BJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031-1037. (Pubitemid 32267972)
108. Druker BJ, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2(5):561-566.
109. Joensuu H, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001;344(14):1052-1056. (Pubitemid 32267975)