IKKβ-mediated Resistance to Skin Cancer Development is ......2017/06/02 · 1 IKKβ-mediated Resistance to Skin Cancer Development is Ink4a/Arf-dependent Angustias Page 1, 2 ,3,
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1
IKKβ-mediated Resistance to Skin Cancer Development
is Ink4a/Arf-dependent
Angustias Page 1, 2 ,3, Ana Bravo 4, Cristian Suarez-Cabrera 1, 2, 3, Josefa P.
Alameda 1, 2, 3, M. Llanos Casanova 1, 2, 3, Corina Lorz 1, 2, 3, Carmen Segrelles 1,
2, 3, José C. Segovia 5, 6, Jesús M. Paramio 1, 2, 3, Manuel Navarro 1, 2, 3, Angel
Ramirez 1, 2, 3
1 Molecular Oncology Unit. Centro de Investigaciones Energéticas,
Medioambientales y Tecnológicas (CIEMAT), 28040 Madrid, Spain.
2 Oncogenomic Unit, Institute of Biomedical Investigation “12 de Octubre i+12”,
28041 Madrid, Spain.
3 Centro de Investigación Biomédica en Red de Cáncer (CIBERONC).
4 Department of Anatomy, Animal Production and Veterinary Clinical Sciences,
Faculty of Veterinary Medicine, University of Santiago de Compostela, 27002
Lugo, Spain.
5 Hematopoietic Innovative Therapies Division. Centro de Investigaciones
Energéticas, Medioambientales y Tecnológicas (CIEMAT). Centro de
Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER).
28040 Madrid, Spain.
6 Advanced Therapies Mixed Unit. Instituto de Investigación Sanitaria-
Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain.
Running title: Anti-tumoral Activity of IKKβ in Skin
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
1. Xia Y, Shen S, Verma IM. NF-kappaB, an active player in human cancers. Cancer Immunol Res 2014;2(9):823-30.
2. Xia Y, Padre RC, De Mendoza TH, Bottero V, Tergaonkar VB, Verma IM. Phosphorylation of p53 by IkappaB kinase 2 promotes its degradation by beta-TrCP. Proc Natl Acad Sci U S A 2009;106(8):2629-34 doi 10.1073/pnas.0812256106.
3. Guo Y, Yuan C, Weghorst CM, Li J. IKKbeta specifically binds to P16 and phosphorylates Ser8 of P16. Biochem Biophys Res Commun 2010;393(3):504-8 doi 10.1016/j.bbrc.2010.02.035.
4. Espinosa L, Margalef P, Bigas A. Non-conventional functions for NF-kappaB members: the dark side of NF-kappaB. Oncogene 2015;34(18):2279-87 doi 10.1038/onc.2014.188.
5. Hinz M, Scheidereit C. The IkappaB kinase complex in NF-kappaB regulation and beyond. EMBO Rep 2014;15(1):46-61 doi 10.1002/embr.201337983.
6. Oeckinghaus A, Hayden MS, Ghosh S. Crosstalk in NF-kappaB signaling pathways. Nat Immunol 2011;12(8):695-708 doi 10.1038/ni.2065.
7. Krishnan RK, Nolte H, Sun T, Kaur H, Sreenivasan K, Looso M, et al. Quantitative analysis of the TNF-alpha-induced phosphoproteome reveals AEG-1/MTDH/LYRIC as an IKKbeta substrate. Nature communications 2015;6:6658 doi 10.1038/ncomms7658.
8. Kim C, Pasparakis M. Epidermal p65/NF-kappaB signalling is essential for skin carcinogenesis. EMBO Mol Med 2014;6(7):970-83 doi 10.15252/emmm.201303541.
9. van Hogerlinden M, Rozell BL, Toftgard R, Sundberg JP. Characterization of the progressive skin disease and inflammatory cell infiltrate in mice with inhibited NF-kappaB signaling. J Invest Dermatol 2004;123(1):101-8 doi 10.1111/j.0022-202X.2004.22706.x.
10. Alameda JP, Moreno-Maldonado R, Jesus Fernandez-Acenero M, Navarro M, Page A, Jorcano JL, et al. Increased IKK alpha Expression in the Basal Layer of the Epidermis of Transgenic Mice Enhances the Malignant Potential of Skin Tumors. Plos One 2011;6(7) doi 10.1371/journal.pone.0021984.
11. Liu B, Park E, Zhu F, Bustos T, Liu J, Shen J, et al. A critical role for I kappaB kinase alpha in the development of human and mouse squamous cell carcinomas. Proc Natl Acad Sci U S A 2006;103(46):17202-7.
12. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, et al. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004;118(3):285-96.
13. Maeda S, Kamata H, Luo JL, Leffert H, Karin M. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 2005;121(7):977-90.
14. Vlantis K, Wullaert A, Sasaki Y, Schmidt-Supprian M, Rajewsky K, Roskams T, et al. Constitutive IKK2 activation in intestinal epithelial cells induces intestinal tumors in mice. J Clin Invest 2011;121(7):2781-93 doi 10.1172/jci45349.
15. Ling J, Kang Y, Zhao R, Xia Q, Lee DF, Chang Z, et al. KrasG12D-induced IKK2/beta/NF-kappaB activation by IL-1alpha and p62 feedforward loops is
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
required for development of pancreatic ductal adenocarcinoma. Cancer Cell 2012;21(1):105-20 doi 10.1016/j.ccr.2011.12.006.
16. Maniati E, Bossard M, Cook N, Candido JB, Emami-Shahri N, Nedospasov SA, et al. Crosstalk between the canonical NF-kappaB and Notch signaling pathways inhibits Ppargamma expression and promotes pancreatic cancer progression in mice. J Clin Invest 2011;121(12):4685-99 doi 10.1172/jci45797.
17. Xia Y, Yeddula N, Leblanc M, Ke E, Zhang Y, Oldfield E, et al. Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model. Nat Cell Biol 2012;14(3):257-65 doi 10.1038/ncb2428.
18. Yang J, Hawkins OE, Barham W, Gilchuk P, Boothby M, Ayers GD, et al. Myeloid IKKbeta promotes antitumor immunity by modulating CCL11 and the innate immune response. Cancer Res 2014;74(24):7274-84 doi 10.1158/0008-5472.can-14-1091.
19. Page A, Cascallana JL, Casanova ML, Navarro M, Alameda JP, Perez P, et al. IKKbeta overexpression leads to pathologic lesions in stratified epithelia and exocrine glands and to tumoral transformation of oral epithelia. Mol Cancer Res 2011;9(10):1329-38 doi 10.1158/1541-7786.mcr-11-0168.
20. Page A, Navarro M, Garin M, Perez P, Llanos Casanova M, Moreno R, et al. IKK beta Leads to an Inflammatory Skin Disease Resembling Interface Dermatitis. Journal of Investigative Dermatology 2010;130(6):1598-610 doi 10.1038/jid.2010.28.
21. Spalding JW, Momma J, Elwell MR, Tennant RW. Chemically induced skin carcinogenesis in a transgenic mouse line (TG.AC) carrying a v-Ha-ras gene. Carcinogenesis 1993;14(7):1335-41.
22. Jonkers J, Meuwissen R, van der Gulden H, Peterse H, van der Valk M, Berns A. Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat Genet 2001;29(4):418-25 doi 10.1038/ng747.
23. Page A, Navarro M, Suarez-Cabrera C, Alameda JP, Casanova ML, Paramio JM, et al. Protective role of p53 in skin cancer: Carcinogenesis studies in mice lacking epidermal p53. Oncotarget 2016;7(15):20902-18 doi 10.18632/oncotarget.7897.
24. Serrano M, Lee H, Chin L, Cordon-Cardo C, Beach D, DePinho RA. Role of the INK4a locus in tumor suppression and cell mortality. Cell 1996;85(1):27-37.
25. Matheu A, Pantoja C, Efeyan A, Criado LM, Martin-Caballero J, Flores JM, et al. Increased gene dosage of Ink4a/Arf results in cancer resistance and normal aging. Genes Dev 2004;18(22):2736-46 doi 10.1101/gad.310304.
26. Leder A, Kuo A, Cardiff RD, Sinn E, Leder P. v-Ha-ras transgene abrogates the initiation step in mouse skin tumorigenesis: effects of phorbol esters and retinoic acid. Proc Natl Acad Sci U S A 1990;87(23):9178-82.
27. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144(5):646-74 doi 10.1016/j.cell.2011.02.013.
28. Wong CE, Yu JS, Quigley DA, To MD, Jen KY, Huang PY, et al. Inflammation and Hras signaling control epithelial-mesenchymal transition during skin tumor progression. Genes Dev 2013;27(6):670-82.
29. Trempus CS, Morris RJ, Bortner CD, Cotsarelis G, Faircloth RS, Reece JM, et al. Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34. J Invest Dermatol 2003;120(4):501-11 doi 10.1046/j.1523-1747.2003.12088.x.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
30. Trempus CS, Morris RJ, Ehinger M, Elmore A, Bortner CD, Ito M, et al. CD34 expression by hair follicle stem cells is required for skin tumor development in mice. Cancer Res 2007;67(9):4173-81 doi 10.1158/0008-5472.can-06-3128.
31. Lapouge G, Beck B, Nassar D, Dubois C, Dekoninck S, Blanpain C. Skin squamous cell carcinoma propagating cells increase with tumour progression and invasiveness. EMBO J 2012;31(24):4563-75 doi 10.1038/emboj.2012.312.
32. Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P, et al. Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling. Nature 2008;452(7187):650-3 doi 10.1038/nature06835.
33. Martinez-Cruz AB, Santos M, Lara MF, Segrelles C, Ruiz S, Moral M, et al. Spontaneous squamous cell carcinoma induced by the somatic inactivation of retinoblastoma and Trp53 tumor suppressors. Cancer Res 2008;68(3):683-92.
34. Rinker MH, Fenske NA, Scalf LA, Glass LF. Histologic variants of squamous cell carcinoma of the skin. Cancer Control 2001;8(4):354-63.
35. Li Q, Van Antwerp D, Mercurio F, Lee KF, Verma IM. Severe liver degeneration in mice lacking the IkappaB kinase 2 gene. Science 1999;284(5412):321-5.
36. Tanaka M, Fuentes ME, Yamaguchi K, Durnin MH, Dalrymple SA, Hardy KL, et al. Embryonic lethality, liver degeneration, and impaired NF-kappa B activation in IKK-beta-deficient mice. Immunity 1999;10(4):421-9.
37. Pasparakis M, Courtois G, Hafner M, Schmidt-Supprian M, Nenci A, Toksoy A, et al. TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature 2002;417(6891):861-6.
38. Pannicke U, Baumann B, Fuchs S, Henneke P, Rensing-Ehl A, Rizzi M, et al. Deficiency of innate and acquired immunity caused by an IKBKB mutation. N Engl J Med 2013;369(26):2504-14 doi 10.1056/NEJMoa1309199.
39. DiDonato JA, Mercurio F, Karin M. NF-kappaB and the link between inflammation and cancer. Immunol Rev 2012;246(1):379-400 doi 10.1111/j.1600-065X.2012.01099.x.
40. Reid MA, Lowman XH, Pan M, Tran TQ, Warmoes MO, Ishak Gabra MB, et al. IKKbeta promotes metabolic adaptation to glutamine deprivation via phosphorylation and inhibition of PFKFB3. Genes Dev 2016;30(16):1837-51 doi 10.1101/gad.287235.116.
41. Chen C, Cao F, Bai L, Liu Y, Xie J, Wang W, et al. IKKbeta Enforces a LIN28B/TCF7L2 Positive Feedback Loop That Promotes Cancer Cell Stemness and Metastasis. Cancer Res 2015;75(8):1725-35 doi 10.1158/0008-5472.can-14-2111.
42. Evaristo C, Spranger S, Barnes SE, Miller ML, Molinero LL, Locke FL, et al. Cutting Edge: Engineering Active IKKbeta in T Cells Drives Tumor Rejection. J Immunol 2016;196(7):2933-8 doi 10.4049/jimmunol.1501144.
43. Koliaraki V, Pasparakis M, Kollias G. IKKbeta in intestinal mesenchymal cells promotes initiation of colitis-associated cancer. J Exp Med 2015;212(13):2235-51 doi 10.1084/jem.20150542.
44. Pallangyo CK, Ziegler PK, Greten FR. IKKbeta acts as a tumor suppressor in cancer-associated fibroblasts during intestinal tumorigenesis. J Exp Med 2015;212(13):2253-66 doi 10.1084/jem.20150576.
45. Ak P, Levine AJ. p53 and NF-kappaB: different strategies for responding to stress lead to a functional antagonism. FASEB J 2010;24(10):3643-52 doi 10.1096/fj.10-160549.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
46. Baker DJ, Perez-Terzic C, Jin F, Pitel KS, Niederlander NJ, Jeganathan K, et al. Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency. Nat Cell Biol 2008;10(7):825-36 doi 10.1038/ncb1744.
47. Sharpless NE, Ramsey MR, Balasubramanian P, Castrillon DH, DePinho RA. The differential impact of p16(INK4a) or p19(ARF) deficiency on cell growth and tumorigenesis. Oncogene 2004;23(2):379-85 doi 10.1038/sj.onc.1207074.
48. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012;2(5):401-4 doi 10.1158/2159-8290.CD-12-0095.
49. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 2013;6(269):pl1 doi 10.1126/scisignal.2004088.
50. Hernandez L, Hsu SC, Davidson B, Birrer MJ, Kohn EC, Annunziata CM. Activation of NF-kappaB signaling by inhibitor of NF-kappaB kinase beta increases aggressiveness of ovarian cancer. Cancer Res 2010;70(10):4005-14 doi 10.1158/0008-5472.CAN-09-3912.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on June 5, 2017; DOI: 10.1158/1541-7786.MCR-17-0157