title: Ultraviolet radiation-induced non-melanoma skin cancer: Regulation of DNA damage repair and inflammation.
abstract: Exposure to ultraviolet (UV) radiation is associated with approximately 65% of melanoma cases, and 90% of non-melanoma skin cancers (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). While the incidence of most other malignancies has either stabilized or declined, that of NMSC has increased and is developing even in younger age groups. NMSCs account for nearly 15,000 deaths, 3.5 million new cases, and more than 3 billion dollars a year in medical costs in the United States alone, representing a major public health concern. As sun protection efforts have not been proven effective, targeted chemoprevention strategies are much needed. Skin carcinogenesis by DNA damage is considered a predominant paradigm for UV toxicity. Exposure to UV radiation can activate various oncogenes while inactivating tumor suppressor genes, resulting in inappropriate survival and proliferation of keratinocytes that harbor these damages. Moreover, increasing evidence demonstrate that inflammatory responses by the immune cells within the tumor microenvironment also contribute significantly to skin tumorigenesis. Initiation and progression of skin carcinogenesis mediated by UV radiation involve complex pathways, including those of apoptosis, proliferation, autophagy, DNA repair, checkpoint signaling, metabolism, and inflammation. In this review, we highlight the recent advances in two of these key molecular processes that result in UV-mediated skin carcinogenesis. In particular, we discuss 1) pathways that regulate DNA damage repair and 2) the regulation of the inflammatory process its crosstalk with DNA repair potentially leading to non-melanoma skin carcinogenesis.
authors: Pritzker School of Medicine, University of Chicago, Chicago, IL, USA.
authors: Young
authors: Y
authors: Kim
authors: Section of Dermatology, Department of Medicine, University of Chicago, Chicago, IL, USA.
authors: Yu-Ying
authors: YY
authors: He
keywords: DNA damage; DNA repair; Inflammation; Skin cancer; UV; Ultraviolet radiation
references: Mol Immunol. 2010 Mar;47(6):1317-24
references: 20005572
references: Nat Rev Mol Cell Biol. 2008 Aug;9(8):628-38
references: 18628784
references: J Leukoc Biol. 2009 Apr;85(4):673-83
references: 19164127
references: Cancer Res. 2006 Aug 15;66(16):8116-22
references: 16912189
references: Neoplasia. 2009 Sep;11(9):846-55
references: 19724678
references: Nucleic Acids Res. 2005 Jul 19;33(13):4023-34
references: 16030353
references: Trends Genet. 1997 Oct;13(10):410-4
references: 9351343
references: J Am Acad Dermatol. 2010 Apr;62(4):573-81
references: 20133012
references: J Invest Dermatol. 2012 Mar;132(3 Pt 2):785-96
references: 22217736
references: Cancer Res. 2013 Apr 1;73(7):2181-8
references: 23382047
references: J Invest Dermatol. 1998 Apr;110(4):405-9
references: 9540983
references: Cancer Res. 2008 May 15;68(10):3992-8
references: 18483286
references: Cancer. 2012 Oct 1;118(19):4768-76
references: 22644960
references: Cancer Res. 2009 Apr 1;69(7):3105-13
references: 19318560
references: Int J Mol Med. 2005 Nov;16(5):943-50
references: 16211268
references: J Biol Chem. 2014 Sep 19;289(38):26658-26668
references: 25112869
references: J Biol Chem. 2005 Apr 22;280(16):15635-43
references: 15723831
references: Cell. 2010 Apr 2;141(1):39-51
references: 20371344
references: Photochem Photobiol. 1996 Apr;63(4):356-7
references: 8934734
references: Nature. 2014 Mar 6;507(7490):109-13
references: 24572365
references: Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10124-8
references: 1946433
references: Mol Carcinog. 2015 Oct;54(10):1026-36
references: 24798404
references: Arch Biochem Biophys. 2000 Apr 15;376(2):338-46
references: 10775421
references: Curr Opin Genet Dev. 2010 Feb;20(1):65-71
references: 20036794
references: Nucleic Acids Res. 2007;35(16):5338-50
references: 17693435
references: Cancer Res. 2006 Mar 15;66(6):2962-9
references: 16540644
references: Cell Cycle. 2009 Jul 15;8(14):2198-210
references: 19502790
references: Arch Dermatol. 1998 Jan;134(1):25-30
references: 9449906
references: J Leukoc Biol. 1994 Dec;56(6):769-75
references: 7996051
references: Cancer Res. 2011 Aug 1;71(15):5287-95
references: 21771908
references: Oncogene. 2006 Oct 30;25(51):6680-4
references: 17072321
references: Oncogene. 2002 Jan 3;21(1):53-64
references: 11791176
references: Annu Rev Pathol. 2010;5:253-95
references: 20078221
references: Nature. 2010 Jan 14;463(7278):191-6
references: 20016485
references: Nat Rev Mol Cell Biol. 2003 May;4(5):361-72
references: 12728270
references: Arch Dermatol. 1994 Aug;130(8):1018-21
references: 8053698
references: Mol Carcinog. 1999 Aug;25(4):231-40
references: 10449029
references: Gastroenterology. 2007 Mar;132(3):905-12
references: 17324405
references: J Invest Dermatol. 2014 Jun;134(6):1710-1717
references: 24326454
references: J Invest Dermatol. 2008 Nov;128(11):2716-2727
references: 18509359
references: Dermatol Surg. 2001 Dec;27(12):1035-8
references: 11849266
references: Mol Cancer Ther. 2010 Mar;9(3):569-80
references: 20145019
references: Science. 2002 May 31;296(5573):1634-5
references: 12040173
references: Cell. 2005 May 6;121(3):387-400
references: 15882621
references: J Invest Dermatol. 2014 Sep;134(9):2315-2320
references: 24786223
references: Cancer Res. 1993 Feb 15;53(4):728-32
references: 8094030
references: Curr Opin Genet Dev. 2014 Jun;26:24-32
references: 25005742
references: Arch Dermatol Res. 2013 Nov;305(9):805-15
references: 23942756
references: Nat Rev Cancer. 2004 Jan;4(1):23-35
references: 14681688
references: Mol Carcinog. 2008 Dec;47(12):974-83
references: 18449856
references: Oncogene. 2013 May 23;32(21):2682-9
references: 22751115
references: J Exp Med. 1993 Oct 1;178(4):1223-30
references: 8104230
references: Carcinogenesis. 1984 Apr;5(4):511-4
references: 6705149
references: Cancer Prev Res (Phila). 2014 Jan;7(1):54-64
references: 24196830
references: Cancer Res. 2008 Sep 1;68(17):6908-12
references: 18757404
references: Cancer Res. 2007 Nov 15;67(22):10879-88
references: 18006833
references: Eur J Immunol. 2001 Aug;31(8):2448-57
references: 11500829
references: Nucleic Acids Res. 1993 Aug 25;21(17):4111-8
references: 8371985
references: J Exp Med. 2002 Jan 7;195(1):99-111
references: 11781369
references: J Biol Chem. 2010 Apr 9;285(15):11458-64
references: 20100829
references: Blood. 2008 Mar 1;111(5):2704-13
references: 18086870
references: Mol Carcinog. 2003 Oct;38(2):49-58
references: 14502644
references: Nat Rev Genet. 2009 Nov;10(11):756-68
references: 19809470
references: Cancer Res. 1999 Jul 15;59(14):3468-74
references: 10416612
references: Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22623-8
references: 21149730
references: Arch Dermatol. 1995 Feb;131(2):170-5
references: 7857113
references: Toxicol Appl Pharmacol. 2007 Nov 1;224(3):220-7
references: 17239911
references: Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14960-5
references: 8962164
references: Cancer Res. 2011 Oct 15;71(20):6382-90
references: 21878529
references: Am J Pathol. 2010 Aug;177(2):555-62
references: 20616346
references: Nature. 1993 Sep 2;365(6441):61-5
references: 7689702
references: J Invest Dermatol. 2009 Jul;129(7):1666-74
references: 19131946
references: Carcinogenesis. 2009 Jul;30(7):1073-81
references: 19468060
references: Curr Biol. 2005 Jan 26;15(2):105-15
references: 15668165
references: Mol Cell Biol. 1998 Jul;18(7):4391-9
references: 9632823
references: Cell. 2007 Jan 12;128(1):157-70
references: 17218262
references: Nat Rev Cancer. 2005 Jul;5(7):564-73
references: 16069818
references: Free Radic Biol Med. 2007 Jan 15;42(2):299-310
references: 17189835
references: Cancer Prev Res (Phila). 2012 Sep;5(9):1155-62
references: 22846842
references: J Biol Chem. 2012 May 25;287(22):18788-95
references: 22500024
references: J Invest Dermatol. 2013 Feb;133(2):296-302
references: 22931928
references: FASEB J. 2005 Jul;19(9):1193-5
references: 15837718
references: Mol Carcinog. 2007 Aug;46(8):624-8
references: 17477367
references: Nat Rev Mol Cell Biol. 2008 Apr;9(4):297-308
references: 18285803
references: Lancet. 1999 Aug 28;354(9180):723-9
references: 10475183
references: Proc Natl Acad Sci U S A. 1974 Sep;71(9):3363-6
references: 4530308
references: Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11366-70
references: 8248255
references: Nat Cell Biol. 2002 Jan;4(1):26-31
references: 11780128
references: Carcinogenesis. 1999 Oct;20(10):1939-44
references: 10506108
references: J Biol Chem. 2009 Sep 4;284(36):24281-8
references: 19586904
references: Mol Carcinog. 2003 Sep;38(1):33-9
references: 12949841
references: Nat Med. 2007 Sep;13(9):1050-9
references: 17704786
references: Science. 1988 Oct 28;242(4878):564-7
references: 3175673
references: J Immunol. 2000 Jan 15;164(2):558-61
references: 10623794
references: Genomics. 1995 Sep 1;29(1):62-9
references: 8530102
references: Exp Dermatol. 2014 Aug;23(8):591-5
references: 24962024
references: Biochem Biophys Res Commun. 2001 Feb 2;280(4):1042-7
references: 11162632
references: Br J Cancer. 1996 Oct;74(8):1308-12
references: 8883423
references: J Clin Invest. 1997 Dec 15;100(12):2961-9
references: 9399941
references: J Immunol. 2011 Aug 15;187(4):1664-73
references: 21765012
references: J Am Acad Dermatol. 2010 Apr;62(4):582-90
references: 20133013
references: Oncologist. 1996;1(1 & 2):88-97
references: 10387973
references: Carcinogenesis. 2008 Mar;29(3):455-65
references: 18174245
references: J Am Acad Dermatol. 2005 Dec;53(6):966-72
references: 16310056
references: Mol Cell. 2010 Jul 30;39(2):247-58
references: 20670893
references: Mol Cell Biol. 2003 Jul;23(13):4673-86
references: 12808106
references: Immunol Cell Biol. 1995 Jun;73(3):226-33
references: 7590895
references: Photochem Photobiol. 2012 Sep-Oct;88(5):1184-90
references: 22335604
references: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12985-90
references: 12242345
references: Oncogene. 2009 Aug 13;28(32):2882-93
references: 19503100
references: JAMA. 2005 Aug 10;294(6):681-90
references: 16091570
references: Ann Med. 2007;39(5):335-45
references: 17701476
references: Nat Rev Cancer. 2009 Feb;9(2):123-8
references: 19132007
references: Nat Med. 2012 Aug;18(8):1286-90
references: 22772463
references: J Eur Acad Dermatol Venereol. 2004 Jan;18(1):93-5
references: 14678542
references: Nature. 2001 May 17;411(6835):366-74
references: 11357144
references: Cancer Biol Ther. 2014 Feb;15(2):156-69
references: 24100703
references: J Mol Histol. 2006 Sep;37(5-7):189-202
references: 16858626
references: J Biol Chem. 1993 Oct 5;268(28):21293-300
references: 8407967
references: Cancer Prev Res (Phila). 2013 Jul;6(7):675-85
references: 23682071
references: J Med Genet. 2011 Mar;48(3):168-76
references: 21097776
references: J Cell Mol Med. 2009 Sep;13(9B):3632-43
references: 18681908
references: Mol Cancer Ther. 2006 Apr;5(4):825-32
references: 16648552
references: Cancer Res. 2014 Oct 15;74(20):5925-33
references: 25320180
references: Oncogene. 2003 Feb 20;22(7):1035-44
references: 12592390
references: Mol Carcinog. 2007 Aug;46(8):692-8
references: 17443745
references: Int J Biol Sci. 2009;5(2):147-52
references: 19173036
references: Cancer Res. 2006 Sep 1;66(17):8590-7
references: 16951172
references: Lancet Infect Dis. 2005 Mar;5(3):156-64
references: 15766650
references: EMBO Rep. 2009 Sep;10(9):1036-42
references: 19644500
references: Cancer Metastasis Rev. 2010 Jun;29(2):309-16
references: 20405169
references: Nature. 1993 Apr 22;362(6422):722-8
references: 8469283
references: Carcinogenesis. 1998 May;19(5):723-9
references: 9635856
references: Oncogene. 2015 Jan 15;34(3):357-63
references: 24441046
references: Cell. 2010 Mar 19;140(6):883-99
references: 20303878
references: Cancer Res. 2002 Jun 15;62(12):3395-401
references: 12067981
references: J Biol Chem. 2001 Mar 30;276(13):10229-33
references: 11150311
references: Arch Biochem Biophys. 2011 Apr 15;508(2):171-7
references: 21236239
references: N Engl J Med. 1993 Oct 14;329(16):1147-51
references: 8377777
references: Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11371-5
references: 8248256
references: Arch Dermatol. 2010 Mar;146(3):283-7
references: 20231499
references: Exp Neurol. 2011 Dec;232(2):143-8
references: 21884699
references: Kaohsiung J Med Sci. 2012 Nov;28(11):577-85
references: 23140765
references: Nature. 1990 Aug 9;346(6284):561-4
references: 2165569
references: Cancer Res. 2007 Apr 15;67(8):3785-93
references: 17440092
references: Mol Cell. 1998 Aug;2(2):223-32
references: 9734359
references: Nature. 2003 Jan 23;421(6921):436-40
references: 12540918