Senescence as a modulator of oral squamous cell carcinoma development

Oral Oncology

Volumn 46, Issue 12, 2010, Pages 840-853

  Parkinson, E Kenneth ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Dysplasia; Keratinocyte; Senescence; Squamous cell carcinoma; Telomere

Indexed keywords

CYCLIN D; CYCLIN DEPENDENT KINASE 4; DNA; PROTEIN P14; PROTEIN P16; TELOMERASE;

AUTOCRINE EFFECT; AUTOPHAGY; CANCER GROWTH; CARCINOGENESIS; CELL CYCLE ARREST; CHROMOSOME 17P; CHROMOSOME 3P; CHROMOSOME 9P; DNA BINDING; DNA DAMAGE; DNA REPLICATION; DNA STRAND BREAKAGE; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; MOUTH CARCINOMA; NICK END LABELING; NONHUMAN; OXIDATIVE STRESS; PARACRINE SIGNALING; PRIORITY JOURNAL; RECEPTOR UPREGULATION; REVIEW; SENESCENCE; SQUAMOUS CELL CARCINOMA; TELOMERE;

CARCINOMA, SQUAMOUS CELL; CELL AGING; CELL LINE, TUMOR; FEMALE; GENES, P16; HUMANS; MALE; MOUTH NEOPLASMS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 78650214566     PISSN: 13688375     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.oraloncology.2009.09.009     Document Type: Review

References (184)

1. A. Forastiere, W. Koch, A. Trotti, and D. Sidransky Head and neck cancer N Engl J Med 345 2001 1890 1900
2. A. Merchant, S.S. Husain, M. Hosain, F.F. Fikree, W. Pitiphat, and A.R. Siddiqui Paan without tobacco: an independent risk factor for oral cancer Int J Cancer 86 2000 128 131
3. B.J. Braakhuis, M.P. Tabor, J.A. Kummer, C.R. Leemans, and R.H. Brakenhoff A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications Cancer Res 63 2003 1727 1730
4. P.K. Ha, and J.A. Califano The molecular biology of mucosal field cancerization of the head and neck Crit Rev Oral Biol Med 14 2003 363 369
5. K.D. Hunter, E.K. Parkinson, and P.R. Harrison Profiling early head and neck cancer Nat Rev Cancer 5 2005 127 135
6. M.M. Kim, and J.A. Califano Molecular pathology of head-and-neck cancer Int J Cancer 112 2004 545 553
7. A.P. Cuthbert, J. Bond, D.A. Trott, S. Gill, J. Broni, and A. Marriott Telomerase repressor sequences on chromosome 3 and induction of permanent growth arrest in human breast cancer cells J Natl Cancer Inst 91 1999 37 45
8. S.J. Baker, E.R. Fearon, J.M. Nigro, S.R. Hamilton, A.C. Preisinger, and J.M. Jessup Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas Science 244 1989 217 221
9. N.E. Sharpless, and R.A. DePinho The INK4A/ARF locus and its two gene products Curr Opin Genet Dev 9 1999 22 30
10. M. Braig, S. Lee, C. Loddenkemper, C. Rudolph, A.H. Peters, and B. Schlegelberger Oncogene-induced senescence as an initial barrier in lymphoma development Nature 436 2005 660 665
11. Z. Chen, L.C. Trotman, D. Shaffer, H.K. Lin, Z.A. Dotan, and M. Niki Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis Nature 436 2005 725 730
12. M. Collado, J. Gil, A. Efeyan, C. Guerra, A.J. Schuhmacher, and M. Barradas Tumour biology: senescence in premalignant tumours Nature 436 2005 642
13. C. Michaloglou, L.C. Vredeveld, M.S. Soengas, C. Denoyelle, T. Kuilman, and C.M. van der Horst BRAFE600-associated senescence-like cell cycle arrest of human naevi Nature 436 2005 720 724
14. C.A. Schmitt, J.S. Fridman, M. Yang, S. Lee, E. Baranov, and R.M. Hoffman A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy Cell 109 2002 335 346
15. L. Hayflick, and P.S. Moorhead The serial cultivation of human diploid cell strains Exp Cell Res 25 1961 585 621
16. G.P. Dimri, X. Lee, G. Basile, M. Acosta, G. Scott, and C. Roskelley A biomarker that identifies senescent human cells in culture and in aging skin in vivo Proc Natl Acad Sci USA 92 1995 9363 9367
17. U. Herbig, M. Ferreira, L. Condel, D. Carey, and J.M. Sedivy Cellular senescence in aging primates Science 311 2006 1257
18. J.C. Jeyapalan, M. Ferreira, J.M. Sedivy, and U. Herbig Accumulation of senescent cells in mitotic tissue of aging primates Mech Ageing Dev 128 2007 36 44
19. S. Goldstein, and D.P. Singal Senescence of cultured human fibroblasts: mitotic versus metabolic time Exp Cell Res 88 1974 359 364
20. A.M. Olovnikov A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon J Theor Biol 41 1973 181 190
21. V.L. Makarov, Y. Hirose, and J.P. Langmore Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening Cell 88 1997 657 666
22. C.B. Harley, A.B. Futcher, and C.W. Greider Telomeres shorten during ageing of human fibroblasts Nature 345 1990 458 460
23. R.C. Allsopp, E. Chang, M. Kashefi-Aazam, E.I. Rogaev, M.A. Piatyszek, and J.W. Shay Telomere shortening is associated with cell division in vitro and in vivo Exp Cell Res 220 1995 194 200
24. J. Munro, K. Steeghs, V. Morrison, H. Ireland, and E.K. Parkinson Human fibroblast replicative senescence can occur in the absence of extensive cell division and short telomeres Oncogene 20 2001 3541 3552
25. C.W. Greider, and E.H. Blackburn Identification of a specific telomere terminal transferase activity in Tetrahymena extracts Cell 43 1985 405 413
26. N.W. Kim, M.A. Piatyszek, K.R. Prowse, C.B. Harley, M.D. West, and P.L. Ho Specific association of human telomerase activity with immortal cells and cancer Science 266 1994 2011 2015
27. S.L. Weinrich, R. Pruzan, L. Ma, M. Ouellette, V.M. Tesmer, and S.E. Holt Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT Nat Genet 17 1997 498 502
28. A.G. Bodnar, M. Ouellette, M. Frolkis, S.E. Holt, C.P. Chiu, and G.B. Morin Extension of life-span by introduction of telomerase into normal human cells Science 279 1998 349 352
29. X.R. Jiang, G. Jimenez, E. Chang, M. Frolkis, B. Kusler, and M. Sage Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype Nat Genet 21 1999 111 114
30. C.P. Morales, S.E. Holt, M. Ouellette, K.J. Kaur, Y. Yan, and K.S. Wilson Absence of cancer-associated changes in human fibroblasts immortalized with telomerase Nat Genet 21 1999 115 118
31. C.M. Counter, W.C. Hahn, W. Wei, S.D. Caddle, R.L. Beijersbergen, and P.M. Lansdorp Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization Proc Natl Acad Sci USA 95 1998 14723 14728
32. Y. Liu, B.E. Snow, M.P. Hande, D. Yeung, N.J. Erdmann, and A. Wakeham The telomerase reverse transcriptase is limiting and necessary for telomerase function in vivo Curr Biol 10 2000 1459 1462
33. M.A. Blasco, H.W. Lee, M.P. Hande, E. Samper, P.M. Lansdorp, and R.A. DePinho Telomere shortening and tumor formation by mouse cells lacking telomerase RNA Cell 91 1997 25 34
34. T. Vulliamy, A. Marrone, F. Goldman, A. Dearlove, M. Bessler, and P.J. Mason The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita Nature 413 2001 432 435 (Pubitemid 32928599)
35. T.J. Vulliamy, A. Walne, A. Baskaradas, P.J. Mason, A. Marrone, and I. Dokal Mutations in the reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure Blood Cells Mol Dis 34 2005 257 263
36. I. Dokal Dyskeratosis congenita in all its forms Br J Haematol 110 2000 768 779
37. K.L. Rudolph, S. Chang, H.W. Lee, M. Blasco, G.J. Gottlieb, and C. Greider Longevity, stress response, and cancer in aging telomerase-deficient mice Cell 96 1999 701 712
38. D.M. Baird, J. Rowson, D. Wynford-Thomas, and D. Kipling Extensive allelic variation and ultrashort telomeres in senescent human cells Nat Genet 33 2003 203 207
39. F. d'Adda di Fagagna, P.M. Reaper, L. Clay-Farrace, H. Fiegler, P. Carr, and T. Von Zglinicki A DNA damage checkpoint response in telomere-initiated senescence Nature 426 2003 194 198
40. F.A. Mallette, M.F. Gaumont-Leclerc, and G. Ferbeyre The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence Genes Dev 21 2007 43 48 (Pubitemid 46089705)
41. U. Herbig, W.A. Jobling, B.P. Chen, D.J. Chen, and J.M. Sedivy Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a) Mol Cell 14 2004 501 513
42. A. Noda, Y. Ning, S.F. Venable, O.M. Pereira-Smith, and J.R. Smith Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen Exp Cell Res 211 1994 90 98
43. V. Dulic, L.F. Drullinger, E. Lees, S.I. Reed, and G.H. Stein Altered regulation of G1 cyclins in senescent human diploid fibroblasts: accumulation of inactive cyclin E-Cdk2 and cyclin D1-Cdk2 complexes Proc Natl Acad Sci USA 90 1993 11034 11038
44. D.A. Alcorta, Y. Xiong, D. Phelps, G. Hannon, D. Beach, and J.C. Barrett Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts Proc Natl Acad Sci USA 93 1996 13742 13747
45. G.H. Stein, M. Beeson, and L. Gordon Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts Science 249 1990 666 669
46. G.P. Dimri, E. Hara, and J. Campisi Regulation of two E2F-related genes in presenescent and senescent human fibroblasts J Biol Chem 269 1994 16180 16186
47. G.H. Stein, L.F. Drullinger, R.S. Robetorye, O.M. Pereira-Smith, and J.R. Smith Senescent cells fail to express cdc2, cycA, and cycB in response to mitogen stimulation Proc Natl Acad Sci USA 88 1991 11012 11016
48. S.J. Robles, and G.R. Adami Agents that cause DNA double strand breaks lead to p16INK4a enrichment and the premature senescence of normal fibroblasts Oncogene 16 1998 1113 1123
49. M. Narita, S. Nunez, E. Heard, M. Narita, A.W. Lin, and S.A. Hearn Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence Cell 113 2003 703 716
50. D.J. Kurz, S. Decary, Y. Hong, and J.D. Erusalimsky Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells J Cell Sci 113 Pt. 20 2000 3613 3622
51. J.J. Jacobs, and T. de Lange Significant role for p16INK4a in p53-independent telomere-directed senescence Curr Biol 14 2004 2302 2308
52. J. Bartkova, N. Rezaei, M. Liontos, P. Karakaidos, D. Kletsas, and N. Issaeva Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints Nature 444 2006 633 637
53. R. Funayama, and F. Ishikawa Cellular senescence and chromatin structure Chromosoma 116 2007 431 440
54. N. Ohtani, Z. Zebedee, T.J. Huot, J.A. Stinson, M. Sugimoto, and Y. Ohashi Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence Nature 409 2001 1067 1070
55. H. Iwasa, J. Han, and F. Ishikawa Mitogen-activated protein kinase p38 defines the common senescence-signalling pathway Genes Cells 8 2003 131 144 (Pubitemid 36511698)
56. N.D. Hastie, M. Dempster, M.G. Dunlop, A.M. Thompson, D.K. Green, and R.C. Allshire Telomere reduction in human colorectal carcinoma and with ageing Nature 346 1990 866 868
57. A.K. Meeker, J.L. Hicks, C.A. Iacobuzio-Donahue, E.A. Montgomery, W.H. Westra, and T.Y. Chan Telomere length abnormalities occur early in the initiation of epithelial carcinogenesis Clin Cancer Res 10 2004 3317 3326
58. J.N. O'Sullivan, M.P. Bronner, T.A. Brentnall, J.C. Finley, W.T. Shen, and S. Emerson Chromosomal instability in ulcerative colitis is related to telomere shortening Nat Genet 32 2002 280 284
59. B. Vukovic, P.C. Park, J. Al-Maghrabi, B. Beheshti, J. Sweet, and A. Evans Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma Oncogene 22 2003 1978 1987
60. D.M. Feldser, and C.W. Greider Short telomeres limit tumor progression in vivo by inducing senescence Cancer Cell 11 2007 461 469
61. J. Bartkova, Z. Horejsi, K. Koed, A. Kramer, F. Tort, and K. Zieger DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis Nature 434 2005 864 870
62. V.G. Gorgoulis, L.V. Vassiliou, P. Karakaidos, P. Zacharatos, A. Kotsinas, and T. Liloglou Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions Nature 434 2005 907 913 (Pubitemid 40559004)
63. J. Choi, I. Shendrik, M. Peacocke, D. Peehl, R. Buttyan, and E.F. Ikeguchi Expression of senescence-associated beta-galactosidase in enlarged prostates from men with benign prostatic hyperplasia Urology 56 2000 160 166
64. B. McClintock The stability of broken ends of chromosomes in zea mays Genetics 26 1941 234 282
65. W.E. Wright, O.M. Pereira-Smith, and J.W. Shay Reversible cellular senescence: implications for immortalization of normal human diploid fibroblasts Mol Cell Biol 9 1989 3088 3092
66. C.M. Counter, A.A. Avilion, C.E. LeFeuvre, N.G. Stewart, C.W. Greider, and C.B. Harley Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity Embo J 11 1992 1921 1929
67. T.M. Bryan, A. Englezou, L. Dalla-Pozza, M.A. Dunham, and R.R. Reddel Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines Nat Med 3 1997 1271 1274
68. T.M. Bryan, A. Englezou, J. Gupta, S. Bacchetti, and R.R. Reddel Telomere elongation in immortal human cells without detectable telomerase activity Embo J 14 1995 4240 4248
69. V. Lundblad, and E.H. Blackburn An alternative pathway for yeast telomere maintenance rescues est1- senescence Cell 73 1993 347 360
70. S.E. Artandi, S. Chang, S.L. Lee, S. Alson, G.J. Gottlieb, and L. Chin Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice Nature 406 2000 641 645
71. L. Mao, A.K. El-Naggar, Y.H. Fan, J.S. Lee, S.M. Lippman, and S. Kayser Telomerase activity in head and neck squamous cell carcinoma and adjacent tissues Cancer Res 56 1996 5600 5604
72. V. Papadimitrakopoulou, J. Izzo, S.M. Lippman, J.S. Lee, Y.H. Fan, and G. Clayman Frequent inactivation of p16INK4a in oral premalignant lesions Oncogene 14 1997 1799 1803
73. G.Z. Qin, J.Y. Park, S.Y. Chen, and P. Lazarus A high prevalence of p53 mutations in pre-malignant oral erythroplakia Int J Cancer 80 1999 345 348
74. F. McGregor, A. Muntoni, J. Fleming, J. Brown, D.H. Felix, and D.G. MacDonald Molecular changes associated with oral dysplasia progression and acquisition of immortality: potential for its reversal by 5-azacytidine Cancer Res 62 2002 4757 4766
75. K.E. Gordon, H. Ireland, M. Roberts, K. Steeghs, J.A. McCaul, and D.G. MacDonald High levels of telomere dysfunction bestow a selective disadvantage during the progression of human oral squamous cell carcinoma Cancer Res 63 2003 458 467
76. S.E. Artandi, and R.A. DePinho Mice without telomerase: what can they teach us about human cancer? Nat Med 6 2000 852 855
77. V. Defendi, P. Naimski, and M.L. Steinberg Human cells transformed by SV40 revisited: the epithelial cells J Cell Physiol Suppl 2 1982 131 140
78. K.L. Rudolph, M. Millard, M.W. Bosenberg, and R.A. DePinho Telomere dysfunction and evolution of intestinal carcinoma in mice and humans Nat Genet 28 2001 155 159
79. S.R. Hingorani, L. Wang, A.S. Multani, C. Combs, T.B. Deramaudt, and R.H. Hruban Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice Cancer Cell 7 2005 469 483
80. D. Gisselsson, T. Jonson, C. Yu, C. Martins, N. Mandahl, and J. Wiegant Centrosomal abnormalities, multipolar mitoses, and chromosomal instability in head and neck tumours with dysfunctional telomeres Br J Cancer 87 2002 202 207
81. D. Gisselsson, T. Jonson, A. Petersen, B. Strombeck, P. Dal Cin, and M. Hoglund Telomere dysfunction triggers extensive DNA fragmentation and evolution of complex chromosome abnormalities in human malignant tumors Proc Natl Acad Sci USA 98 2001 12683 12688
82. J.W. Shay, and W.E. Wright The reactivation of telomerase activity in cancer progression Trends Genet 12 1996 129 131
83. M.A. Dickson, W.C. Hahn, Y. Ino, V. Ronfard, J.Y. Wu, and R.A. Weinberg Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics Mol Cell Biol 20 2000 1436 1447
84. Y. Cong, and J.W. Shay Actions of human telomerase beyond telomeres Cell Res 18 2008 725 732
85. E.K. Parkinson, C. Fitchett, and B. Cereser Dissecting the non-canonical functions of telomerase Cytogenet Genome Res 122 2008 273 280
86. M. Greaves Is telomerase activity in cancer due to selection of stem cells and differentiation arrest? Trends Genet 12 1996 127 128
87. M.W. Drummond, S. Balabanov, T.L. Holyoake, and T.H. Brummendorf Concise review: telomere biology in normal and leukemic hematopoietic stem cells Stem cells 25 2007 1853 1861
88. T.H. Brummendorf, T.L. Holyoake, N. Rufer, M.J. Barnett, M. Schulzer, and C.J. Eaves Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry Blood 95 2000 1883 1890
89. H. Nakai, and S. Misawa Chromosome 17 abnormalities and inactivation of the p53 gene in chronic myeloid leukemia and their prognostic significance Leuk Lymphoma 19 1995 213 221
90. B. Johansson, T. Fioretos, and F. Mitelman Cytogenetic and molecular genetic evolution of chronic myeloid leukemia Acta Haematol 107 2002 76 94
91. M. Mohty, A.S. Yong, R.M. Szydlo, J.F. Apperley, and J.V. Melo The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia Blood 110 2007 380 383
92. E.K. Parkinson, R.F. Newbold, and W.N. Keith The genetic basis of human keratinocyte immortalisation in squamous cell carcinoma development: the role of telomerase reactivation Eur J Cancer 33 1997 727 734
93. A. Muntoni, J. Fleming, K.E. Gordon, K. Hunter, F. McGregor, and E.K. Parkinson Senescing oral dysplasias are not immortalized by ectopic expression of hTERT alone without other molecular changes, such as loss of INK4A and/or retinoic acid receptor-beta: but p53 mutations are not necessarily required Oncogene 22 2003 7804 7808
94. O. Loughran, A. Malliri, D. Owens, P.H. Gallimore, M.A. Stanley, and B. Ozanne Association of CDKN2A/p16INK4A with human head and neck keratinocyte replicative senescence. relationship of dysfunction to immortality and neoplasia Oncogene 13 1996 561 568
95. E. Natarajan, J.D. Omobono 2nd, Z. Guo, S. Hopkinson, A.J. Lazar, and T. Brenn A keratinocyte hypermotility/growth-arrest response involving laminin 5 and p16INK4A activated in wound healing and senescence Am J Pathol 168 2006 1821 1837
96. E. Natarajan, M. Saeb, C.P. Crum, S.B. Woo, P.H. McKee, and J.G. Rheinwald Co-expression of p16(INK4A) and laminin 5 gamma2 by microinvasive and superficial squamous cell carcinomas in vivo and by migrating wound and senescent keratinocytes in culture Am J Pathol 163 2003 477 491
97. B.W. Darbro, G.B. Schneider, and A.J. Klingelhutz Co-regulation of p16INK4A and migratory genes in culture conditions that lead to premature senescence in human keratinocytes J Invest Dermatol 125 2005 499 509
98. J. Munro, F.J. Stott, K.H. Vousden, G. Peters, and E.K. Parkinson Role of the alternative INK4A proteins in human keratinocyte senescence: evidence for the specific inactivation of p16INK4A upon immortalization Cancer Res 59 1999 2516 2521
99. Y. Barrandon, and H. Green Three clonal types of keratinocyte with different capacities for multiplication Proc Natl Acad Sci USA 84 1987 2302 2306
100. R. Maurelli, G. Zambruno, L. Guerra, C. Abbruzzese, G. Dimri, and M. Gellini Inactivation of p16INK4a (inhibitor of cyclin-dependent kinase 4A) immortalizes primary human keratinocytes by maintaining cells in the stem cell compartment Faseb J 20 2006 1516 1518
101. S. Ressler, J. Bartkova, H. Niederegger, J. Bartek, K. Scharffetter-Kochanek, and P. Jansen-Durr P16INK4A is a robust in vivo biomarker of cellular aging in human skin Aging Cell 5 2006 379 389
102. A. Giangreco, M. Qin, J.E. Pintar, and F.M. Watt Epidermal stem cells are retained in vivo throughout skin aging Aging Cell 7 2008 250 259
103. K. Martin, T.B. Kirkwood, and C.S. Potten Age changes in stem cells of murine small intestinal crypts Exp Cell Res 241 1998 316 323
104. K. Martin, C.S. Potten, S.A. Roberts, and T.B. Kirkwood Altered stem cell regeneration in irradiated intestinal crypts of senescent mice J Cell Sci 111 Pt. 16 1998 2297 2303
105. J. Krishnamurthy, C. Torrice, M.R. Ramsey, G.I. Kovalev, K. Al-Regaiey, and L. Su Ink4a/Arf expression is a biomarker of aging J Clin Invest 114 2004 1299 1307
106. A.V. Molofsky, S.G. Slutsky, N.M. Joseph, S. He, R. Pardal, and J. Krishnamurthy Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing Nature 443 2006 448 452
107. J. Krishnamurthy, M.R. Ramsey, K.L. Ligon, C. Torrice, A. Koh, and S. Bonner-Weir P16INK4a induces an age-dependent decline in islet regenerative potential Nature 443 2006 453 457
108. V. Janzen, R. Forkert, H.E. Fleming, Y. Saito, M.T. Waring, and D.M. Dombkowski Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a Nature 443 2006 421 426
109. P. Krimpenfort, K.C. Quon, W.J. Mooi, A. Loonstra, and A. Berns Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice Nature 413 2001 83 86
110. N.E. Sharpless, N. Bardeesy, K.H. Lee, D. Carrasco, D.H. Castrillon, and A.J. Aguirre Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis Nature 413 2001 86 91
111. V.L. Brown, C.A. Harwood, T. Crook, J.G. Cronin, D.P. Kelsell, and C.M. Proby p16INK4a and p14ARF tumor suppressor genes are commonly inactivated in cutaneous squamous cell carcinoma J Invest Dermatol 122 2004 1284 1292
112. A.L. Reed, J. Califano, P. Cairns, W.H. Westra, R.M. Jones, and W. Koch High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma Cancer Res 56 1996 3630 3633
113. P. Krimpenfort, A. Ijpenberg, J.Y. Song, M. van der Valk, M. Nawijn, and J. Zevenhoven p15Ink4b is a critical tumour suppressor in the absence of p16Ink4a Nature 448 2007 943 946
114. J. Campisi Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors Cell 120 2005 513 522
115. M. Serrano, A.W. Lin, M.E. McCurrach, D. Beach, and S.W. Lowe Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a Cell 88 1997 593 602
116. A.W. Lin, M. Barradas, J.C. Stone, L. van Aelst, M. Serrano, and S.W. Lowe Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling Genes Dev 12 1998 3008 3019
117. J. Zhu, D. Woods, M. McMahon, and J.M. Bishop Senescence of human fibroblasts induced by oncogenic Raf Genes Dev 12 1998 2997 3007
118. S. Drayton, J. Rowe, R. Jones, R. Vatcheva, D. Cuthbert-Heavens, and J. Marshall Tumor suppressor p16INK4a determines sensitivity of human cells to transformation by cooperating cellular oncogenes Cancer Cell 4 2003 301 310
119. C.J. Sarkisian, B.A. Keister, D.B. Stairs, R.B. Boxer, S.E. Moody, and L.A. Chodosh Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis Nat Cell Biol 9 2007 493 505
120. A.C. Lee, B.E. Fenster, H. Ito, K. Takeda, N.S. Bae, and T. Hirai Ras proteins induce senescence by altering the intracellular levels of reactive oxygen species J Biol Chem 274 1999 7936 7940
121. J.A. Benanti, and D.A. Galloway Normal human fibroblasts are resistant to RAS-induced senescence Mol Cell Biol 24 2004 2842 2852
122. M. Dajee, M. Lazarov, J.Y. Zhang, T. Cai, C.L. Green, and A.J. Russell NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia Nature 421 2003 639 643
123. M. Takaoka, H. Harada, T.B. Deramaudt, K. Oyama, C.D. Andl, and C.N. Johnstone Ha-Ras(G12V) induces senescence in primary and immortalized human esophageal keratinocytes with p53 dysfunction Oncogene 23 2004 6760 6768
124. M. Lazarov, Y. Kubo, T. Cai, M. Dajee, M. Tarutani, and Q. Lin CDK4 coexpression with Ras generates malignant human epidermal tumorigenesis Nat Med 8 2002 1105 1114
125. D.R. Henrard, A.T. Thornley, M.L. Brown, and J.G. Rheinwald Specific effects of ras oncogene expression on the growth and histogenesis of human epidermal keratinocytes Oncogene 5 1990 475 481
126. I. Haase, R.M. Hobbs, M.R. Romero, S. Broad, and F.M. Watt A role for mitogen-activated protein kinase activation by integrins in the pathogenesis of psoriasis J Clin Invest 108 2001 527 536
127. A.J. Zhu, I. Haase, and F.M. Watt Signaling via beta1 integrins and mitogen-activated protein kinase determines human epidermal stem cell fate in vitro Proc Natl Acad Sci USA 96 1999 6728 6733
128. A. Gandarillas, and F.M. Watt c-Myc promotes differentiation of human epidermal stem cells Genes Dev 11 1997 2869 2882
129. R.L. Waikel, Y. Kawachi, P.A. Waikel, X.J. Wang, and D.R. Roop Deregulated expression of c-Myc depletes epidermal stem cells Nat Genet 28 2001 165 168
130. J.J. Jacobs, K. Kieboom, S. Marino, R.A. DePinho, and M. van Lohuizen The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus Nature 397 1999 164 168
131. K. Agger, P.A. Cloos, L. Rudkjaer, K. Williams, G. Andersen, and J. Christensen The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence Genes Dev 23 2009 1171 1176
132. M. Barradas, E. Anderton, J.C. Acosta, S. Li, A. Banito, and M. Rodriguez-Niedenfuhr Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS Genes Dev 23 2009 1177 1182
133. M.K. Kang, R.H. Kim, S.J. Kim, F.K. Yip, K.H. Shin, and G.P. Dimri Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival Br J Cancer 96 2007 126 133
134. R. Di Micco, M. Fumagalli, A. Cicalese, S. Piccinin, P. Gasparini, and C. Luise Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication Nature 444 2006 638 642
135. N.J. Clemons, K.E. McColl, and R.C. Fitzgerald Nitric oxide and acid induce double-strand DNA breaks in Barrett's esophagus carcinogenesis via distinct mechanisms Gastroenterology 133 2007 1198 1209
136. E.S. Gonos, J.S. Burns, G.R. Mazars, A. Kobrna, T.E. Riley, and S.C. Barnett Rat embryo fibroblasts immortalized with simian virus 40 large T antigen undergo senescence upon its inactivation Mol Cell Biol 16 1996 5127 5138
137. P.G. Nuciforo, C. Luise, M. Capra, G. Pelosi, and F. d'Adda di Fagagna Complex engagement of DNA damage response pathways in human cancer and in lung tumor progression Carcinogenesis 28 2007 2082 2088
138. F. Minty, J.K. Thurlow, P.R. Harrison, and E.K. Parkinson Telomere dysfunction in human keratinocytes elicits senescence and a novel transcription profile Exp Cell Res 314 2008 2434 2447
139. G.V. Shurin, R.L. Ferris, I.L. Tourkova, L. Perez, A. Lokshin, and L. Balkir Loss of new chemokine CXCL14 in tumor tissue is associated with low infiltration by dendritic cells (DC), while restoration of human CXCL14 expression in tumor cells causes attraction of DC both in vitro and in vivo J Immunol 174 2005 5490 5498
140. C.W. Trenam, D.R. Blake, and C.J. Morris Skin inflammation: reactive oxygen species and the role of iron J Invest Dermatol 99 1992 675 682
141. N.R. Forsyth, A.P. Evans, J.W. Shay, and W.E. Wright Developmental differences in the immortalization of lung fibroblasts by telomerase Aging Cell 2 2003 235 243
142. S. Parrinello, E. Samper, A. Krtolica, J. Goldstein, S. Melov, and J. Campisi Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts Nat Cell Biol 5 2003 741 747
143. J.F. Passos, G. Saretzki, and T. von Zglinicki DNA damage in telomeres and mitochondria during cellular senescence: is there a connection? Nucleic Acids Res 35 2007 7505 7513
144. H. Kondoh, M.E. Lleonart, J. Gil, J. Wang, P. Degan, and G. Peters Glycolytic enzymes can modulate cellular life span Cancer Res 65 2005 177 185
145. H. Kondoh, M.E. Lleonart, Y. Nakashima, M. Yokode, M. Tanaka, and D. Bernard A high glycolytic flux supports the proliferative potential of murine embryonic stem cells Antioxid Redox Signal 9 2007 293 299
146. J. Bartkova, C.J. Bakkenist, E. Rajpert-De Meyts, N.E. Skakkebaek, M. Sehested, and J. Lukas ATM activation in normal human tissues and testicular cancer Cell Cycle 4 2005 838 845
147. R. Nowak, K. Sikora, A. Pietas, I. Skoneczna, and S.J. Chrapusta Germ cell-like telomeric length homeostasis in nonseminomatous testicular germ cell tumors Oncogene 19 2000 4075 4078
148. J. Bartkova, E. Rajpert-De Meyts, N.E. Skakkebaek, J. Lukas, and J. Bartek Deregulation of the G1/S-phase control in human testicular germ cell tumours Apmis 111 2003 252 265 [discussion 65-6]
149. T. Kuilman, C. Michaloglou, L.C. Vredeveld, S. Douma, R. van Doorn, and C.J. Desmet Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network Cell 133 2008 1019 1031
150. J.C. Acosta, A. O'Loghlen, A. Banito, M.V. Guijarro, A. Augert, and S. Raguz Chemokine signaling via the CXCR2 receptor reinforces senescence Cell 133 2008 1006 1018
151. W. Xue, L. Zender, C. Miething, R.A. Dickins, E. Hernando, and V. Krizhanovsky Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas Nature 445 2007 656 660
152. P. Castro, D. Giri, D. Lamb, and M. Ittmann Cellular senescence in the pathogenesis of benign prostatic hyperplasia Prostate 55 2003 30 38
153. R. Pries, and B. Wollenberg Cytokines in head and neck cancer Cytokine Growth Factor Rev 17 2006 141 146
154. A.L. Edinger, and C.B. Thompson Death by design: apoptosis, necrosis and autophagy Curr Opin Cell Biol 16 2004 663 669
155. A.R. Young, M. Narita, M. Ferreira, K. Kirschner, M. Sadaie, and J.F. Darot Autophagy mediates the mitotic senescence transition Genes Dev 23 2009 798 803
156. D. Crighton, S. Wilkinson, J. O'Prey, N. Syed, P. Smith, and P.R. Harrison DRAM, a p53-induced modulator of autophagy, is critical for apoptosis Cell 126 2006 121 134
157. A. Hague, J.W. Eveson, M. MacFarlane, S. Huntley, N. Janghra, and S. Thavaraj Caspase-3 expression is reduced, in the absence of cleavage, in terminally differentiated normal oral epithelium but is increased in oral squamous cell carcinomas and correlates with tumour stage J Pathol 204 2004 175 182
158. M.G. Downey, J.J. Going, R.C. Stuart, and W.N. Keith Expression of telomerase RNA in oesophageal and oral cancer J Oral Pathol Med 30 2001 577 581
159. K. Freier, S. Pungs, C. Flechtenmacher, F.X. Bosch, P. Lichter, and S. Joos Frequent high telomerase reverse transcriptase expression in primary oral squamous cell carcinoma J Oral Pathol Med 36 2007 267 272 (Pubitemid 46632612)
160. A.I. Soder, S.F. Hoare, S. Muir, J.J. Going, E.K. Parkinson, and W.N. Keith Amplification, increased dosage and in situ expression of the telomerase RNA gene in human cancer Oncogene 14 1997 1013 1021
161. H. Szutorisz, J. Lingner, A.P. Cuthbert, D.A. Trott, R.F. Newbold, and M. Nabholz A chromosome 3-encoded repressor of the human telomerase reverse transcriptase (hTERT) gene controls the state of hTERT chromatin Cancer Res 63 2003 689 695
162. B.J. Braakhuis, P.J. Snijders, W.J. Keune, C.J. Meijer, H.J. Ruijter-Schippers, and C.R. Leemans Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus J Natl Cancer Inst 96 2004 998 1006
163. L. Gewin, H. Myers, T. Kiyono, and D.A. Galloway Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex Genes Dev 18 2004 2269 2282
164. M. Xu, W. Luo, D.J. Elzi, C. Grandori, and D.A. Galloway NFX1 interacts with mSin3A/histone deacetylase to repress hTERT transcription in keratinocytes Mol Cell Biol 28 2008 4819 4828
165. M. Scheffner, B.A. Werness, J.M. Huibregtse, A.J. Levine, and P.M. Howley The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53 Cell 63 1990 1129 1136
166. B.A. Werness, A.J. Levine, and P.M. Howley Association of human papillomavirus types 16 and 18 E6 proteins with p53 Science 248 1990 76 79
167. M. Oshimura, and J.C. Barrett Multiple pathways to cellular senescence: role of telomerase repressors Eur J Cancer 33 1997 710 715
168. N.R. Forsyth, V. Morrison, N.J. Craig, S.A. Fitzsimmons, N.I. Barr, and H. Ireland Functional evidence for a squamous cell carcinoma mortality gene(s) on human chromosome 4 Oncogene 21 2002 5135 5147
169. T. Kuilman, and D.S. Peeper Senescence-messaging secretome: SMS-ing cellular stress Nat Rev Cancer 9 2009 81 94
170. J.P. Coppe, C.K. Patil, F. Rodier, Y. Sun, D.P. Munoz, and J. Goldstein Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor PLoS Biol 6 2008 2853 2868
171. A. Krtolica, S. Parrinello, S. Lockett, P.Y. Desprez, and J. Campisi Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging Proc Natl Acad Sci USA 98 2001 12072 12077
172. E. Pazolli, X. Luo, S. Brehm, K. Carbery, J.J. Chung, and J.L. Prior Senescent stromal-derived osteopontin promotes preneoplastic cell growth Cancer Res 69 2009 1230 1239
173. Y.H. Hsieh, M.M. Juliana, P.H. Hicks, G. Feng, C. Elmets, and L. Liaw Papilloma development is delayed in osteopontin-null mice. implicating an
174. R.E. Devoll, W. Li, K.V. Woods, G.J. Pinero, W.T. Butler, and M.C. Farach-Carson Osteopontin (OPN) distribution in premalignant and malignant lesions of oral epithelium and expression in cell lines derived from squamous cell carcinoma of the oral cavity J Oral Pathol Med 28 1999 97 101
175. S. Parrinello, J.P. Coppe, A. Krtolica, and J. Campisi Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation J Cell Sci 118 2005 485 496
176. D. Hanahan, and R.A. Weinberg The hallmarks of cancer Cell 100 2000 57 70
177. G. Yang, D.G. Rosen, Z. Zhang, R.C. Bast Jr., G.B. Mills, and J.A. Colacino The chemokine growth-regulated oncogene 1 (Gro-1) links RAS signaling to the senescence of stromal fibroblasts and ovarian tumorigenesis Proc Natl Acad Sci USA 103 2006 16472 16477
178. K.G. Edington, O.P. Loughran, I.J. Berry, and E.K. Parkinson Cellular immortality: a late event in the progression of human squamous cell carcinoma of the head and neck associated with p53 alteration and a high frequency of allele loss Mol Carcinog 13 1995 254 265
179. J.G. Rheinwald, and M.A. Beckett Tumorigenic keratinocyte lines requiring anchorage and fibroblast support cultures from human squamous cell carcinomas Cancer Res 41 1981 1657 1663
180. K.D. Hunter, J.K. Thurlow, J. Fleming, P.J. Drake, J.K. Vass, and G. Kalna Divergent routes to oral cancer Cancer Res 66 2006 7405 7413
181. J.E. Burns, M.C. Baird, L.J. Clark, P.A. Burns, K. Edington, and C. Chapman Gene mutations and increased levels of p53 protein in human squamous cell carcinomas and their cell lines Br J Cancer 67 1993 1274 1284
182. T. Wiest, E. Schwarz, C. Enders, C. Flechtenmacher, and F.X. Bosch Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control Oncogene 21 2002 1510 1517
183. J.G. Rheinwald, and M.A. Beckett Defective terminal differentiation in culture as a consistent and selectable character of malignant human keratinocytes Cell 22 1980 629 632
184. Y.J. Chen, V. Hakin-Smith, M. Teo, G.E. Xinarianos, D.A. Jellinek, and T. Carroll Association of mutant TP53 with alternative lengthening of telomeres and favorable prognosis in glioma Cancer Res 66 2006 6473 6476