Controversial aspects of oncogene-induced senescence

Cell Cycle

Volumn 11, Issue 22, 2012, Pages 4147-4151

  Bianchi Smiraglia, Anna ^a   Nikiforov, Mikhail A ^a  

^a ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

C MYC; Deoxyribonucleotides; DNA damage; DNA damage response; p53; Ribonucleotide reductase; Thymidylate synthase

Indexed keywords

CHECKPOINT KINASE 1; CYCLIN DEPENDENT KINASE INHIBITOR 2A; PROTEIN P53; RAF PROTEIN; RAS PROTEIN; REACTIVE OXYGEN METABOLITE;

CELL CYCLE PROGRESSION; CELL DEATH; CELL DIFFERENTIATION; CELL PROLIFERATION; DNA DAMAGE; DNA REPLICATION; DOUBLE STRANDED DNA BREAK; FIBROBLAST; GENE FREQUENCY; HUMAN; INHIBITION KINETICS; KERATINOCYTE; MELANOCYTE; NONHUMAN; ONCOGENE; ONCOGENE INDUCED SENESCENCE; PHENOTYPE; PROTEIN DEGRADATION; PROTEIN DEPLETION; PROTEIN PHOSPHORYLATION; REVIEW; SENESCENCE; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE;

EID: 84869478903     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.22589     Document Type: Review

References (107)

1. Hayflick L. The Limited in Vitro Lifetime of Human Diploid Cell Strains. Exp Cell Res 1965; 37:614-36; PMID:14315085; http://dx.doi.org/10.1016/0014- 4827(65)90211-9.
2. Gorgoulis VG, Halazonetis TD. Oncogene-induced senescence: the bright and dark side of the response. Curr Opin Cell Biol 2010; 22:816-27; PMID:20807678; http://dx.doi.org/10.1016/j.ceb.2010.07.013.
3. Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 2005; 120:513-22; PMID:15734683; http://dx.doi.org/10.1016/j.cell.2005.02.003.
4. Marasa BS, Srikantan S, Martindale JL, Kim MM, Lee EK, Gorospe M, et al. MicroRNA profiling in human diploid fibroblasts uncovers miR-519 role in replicative senescence. Aging (Albany NY) 2010; 2:333-43; PMID:20606251.
5. Blagoev KB, Goodwin EH, Bailey SM. Telomere sister chromatid exchange and the process of aging. Aging (Albany NY) 2010; 2:727-30; PMID:20952810.
6. Wagner W, Bork S, Lepperdinger G, Joussen S, Ma N, Strunk D, et al. How to track cellular aging of mesenchymal stromal cells? Aging (Albany NY) 2010; 2:224-30; PMID:20453259.
7. Schellenberg A, Lin Q, Schüler H, Koch CM, Joussen S, Denecke B, et al. Replicative senescence of mesenchymal stem cells causes DNA-methylation changes which correlate with repressive histone marks. Aging (Albany NY) 2011; 3:873-88; PMID:22025769.
8. Chang S. The telomere protein tankyrase 1 regulates DNA damage responses at telomeres. Aging (Albany NY) 2010; 2:639-42; PMID:21076181.
9. Gadalla SM, Cawthon R, Giri N, Alter BP, Savage SA. Telomere length in blood, buccal cells, and fibroblasts from patients with inherited bone marrow failure syndromes. Aging (Albany NY) 2010; 2:867-74; PMID:21113082.
10. Dregalla RC, Zhou J, Idate RR, Battaglia CL, Liber HL, Bailey SM. Regulatory roles of tankyrase 1 at telomeres and in DNA repair: suppression of T-SCE and stabilization of DNA-PKcs. Aging (Albany NY) 2010; 2:691-708; PMID:21037379.
11. Kuhlow D, Florian S, von Figura G, Weimer S, Schulz N, Petzke KJ, et al. Telomerase deficiency impairs glucose metabolism and insulin secretion. Aging (Albany NY) 2010; 2:650-8; PMID:20876939.
12. Brosh RM Jr. Put on your thinking cap: G-quadruplexes, helicases, and telomeres. Aging (Albany NY) 2011; 3:332-5; PMID:21732565.
13. Horikawa I, Fujita K, Harris CC. p53 governs telomere regulation feedback too, via TRF2. Aging (Albany NY) 2011; 3:26-32; PMID:21266744.
14. Wu RT, Cheng WH. New insight into telomere maintenance. Aging (Albany NY) 2010; 2:255-6; PMID:20519779.
15. Gramatges MM, Bertuch AA. Measuring relative telomere length: is tissue an issue? Aging (Albany NY) 2010; 2:756-7; PMID:21113083.
16. Sheppard SA, Loayza D. LIM-domain proteins TRIP6 and LPP associate with shelterin to mediate telomere protection. Aging (Albany NY) 2010; 2:432-44; PMID:20634563.
17. Sell C. Ku circles the telomere? Aging (Albany NY) 2011; 3:344-5; PMID:21732567.
18. Mulder H. Is shortening of telomeres the missing link between aging and the Type 2 Diabetes epidemic? Aging (Albany NY) 2010; 2:634-6; PMID:21076183.
19. Mason M, Skordalakes E. Insights into Cdc13 dependent telomere length regulation. Aging (Albany NY) 2010; 2:731-4; PMID:20975208.
20. Li B, Reddy S, Comai L. Depletion of Ku70/80 reduces the levels of extrachromosomal telomeric circles and inhibits proliferation of ALT cells. Aging (Albany NY) 2011; 3:395-406; PMID:21512205.
21. Kusumoto-Matsuo R, Opresko PL, Ramsden D, Tahara H, Bohr VA. Cooperation of DNA-PKcs and WRN helicase in the maintenance of telomeric D-loops. Aging (Albany NY) 2010; 2:274-84; PMID:20519774.
22. Ishikawa N, Nakamura K, Izumiyama-Shimomura N, Aida J, Ishii A, Goto M, et al. Accelerated in vivo epidermal telomere loss in Werner syndrome. Aging (Albany NY) 2011; 3:417-29; PMID:21732564.
23. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997; 88:593-602; PMID:9054499; http://dx.doi.org/10.1016/S0092-8674(00) 81902-9.
24. Mallette FA, Calabrese V, Ilangumaran S, Ferbeyre G. SOCS1, a novel interaction partner of p53 controlling oncogene-induced senescence. Aging (Albany NY) 2010; 2:445-52; PMID:20622265.
25. Mirisola MG, Longo VD. Conserved role of Ras-GEFs in promoting aging: from yeast to mice. Aging (Albany NY) 2011; 3:340-3; PMID:21732566.
26. Prieur A, Peeper DS. Cellular senescence in vivo: a barrier to tumorigenesis. Curr Opin Cell Biol 2008; 20:150-5; PMID:18353625; http://dx.doi.org/10.1016/j.ceb.2008.01.007.
27. Bringold F, Serrano M. Tumor suppressors and oncogenes in cellular senescence. Exp Gerontol 2000; 35:317-29; PMID:10832053; http://dx.doi. org/10.1016/S0531-5565(00)00083-8.
28. Mooi WJ, Peeper DS. Oncogene-induced cell senescence - halting on the road to cancer. N Engl J Med 2006; 355:1037-46; PMID:16957149; http://dx.doi.org/10.1056/NEJMra062285.
29. Noonan EJ, Place RF, Basak S, Pookot D, Li LC. miR-449a causes Rb-dependent cell cycle arrest and senescence in prostate cancer cells. Oncotarget 2010; 1:349-58; PMID:20948989.
30. Chao SK, Horwitz SB, McDaid HM. Insights into 4E-BP1 and p53 mediated regulation of accelerated cell senescence. Oncotarget 2011; 2:89-98; PMID:21399233.
31. Mercier I, Camacho J, Titchen K, Gonzales DM, Quann K, Bryant KG, et al. Caveolin-1 and accelerated host aging in the breast tumor microenvironment: chemoprevention with rapamycin, an mTOR inhibitor and anti-aging drug. Am J Pathol 2012; 181:278-93; PMID:22698676; http://dx.doi.org/10.1016/j.ajpath.2012. 03.017.
32. Ory B, Ellisen LW. A microRNA-dependent circuit controlling p63/p73 homeostasis: p53 family crosstalk meets therapeutic opportunity. Oncotarget 2011; 2:259-64; PMID:21436470.
33. Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability - an evolving hallmark of cancer. Nat Rev Mol Cell Biol 2010; 11:220-8; PMID:20177397; http://dx.doi.org/10.1038/nrm2858.
34. Martinelli P, Bonetti P, Sironi C, Pruneri G, Fumagalli C, Raviele PR, et al. The lymphoma-associated NPMALK oncogene elicits a p16INK4a/pRb-dependent tumor-suppressive pathway. Blood 2011; 117:6617-26; PMID:21518927; http://dx.doi.org/10.1182/blood-2010-08-301135.
35. Gil J, Peters G. Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all. Nat Rev Mol Cell Biol 2006; 7:667-77; PMID:16921403; http://dx.doi.org/10.1038/nrm1987.
36. Kastan MB. Wild-type p53: tumors can't stand it. Cell 2007; 128:837-40; PMID:17350571; http://dx.doi.org/10.1016/j.cell.2007.02.022.
37. Madan E, Gogna R, Bhatt M, Pati U, Kuppusamy P, Mahdi AA. Regulation of glucose metabolism by p53: emerging new roles for the tumor suppressor. Oncotarget 2011; 2:948-57; PMID:22248668.
38. Odell A, Askham J, Whibley C, Hollstein M. How to become immortal: let MEFs count the ways. Aging (Albany NY) 2010; 2:160-5; PMID:20378935.
39. Larsson LG. Oncogene- and tumor suppressor genemediated suppression of cellular senescence. Semin Cancer Biol 2011; 21:367-76; PMID:22037160; http://dx.doi.org/10.1016/j.semcancer.2011.10.005.
40. Martinez I, Almstead LL, DiMaio D. MicroRNAs and senescence. Aging (Albany NY) 2011; 3:77-8; PMID:21304181.
41. Courtois-Cox S, Jones SL, Cichowski K. Many roads lead to oncogene-induced senescence. Oncogene 2008; 27:2801-9; PMID:18193093; http://dx.doi.org/10.1038/sj.onc.1210950.
42. Collado M, Serrano M. The power and the promise of oncogene-induced senescence markers. Nat Rev Cancer 2006; 6:472-6; PMID:16723993; http://dx.doi.org/10.1038/nrc1884.
43. Galluzzi L, Kepp O, Kroemer G. TP53 and MTOR crosstalk to regulate cellular senescence. Aging (Albany NY) 2010; 2:535-7; PMID:20876940.
44. Poyurovsky MV, Prives C. P53 and aging: A fresh look at an old paradigm. Aging (Albany NY) 2010; 2:380-2; PMID:20657036.
45. Taylor JR, Lehmann BD, Chappell WH, Abrams SL, Steelman LS, McCubrey JA. Cooperative effects of Akt-1 and Raf-1 on the induction of cellular senescence in doxorubicin or tamoxifen treated breast cancer cells. Oncotarget 2011; 2:610-26; PMID:21881167.
46. Xu M, Yu Q, Subrahmanyam R, Difilippantonio MJ, Ried T, Sen JM. Beta-catenin expression results in p53-independent DNA damage and oncogene-induced senescence in prelymphomagenic thymocytes in vivo. Mol Cell Biol 2008; 28:1713-23; PMID:18160717; http://dx.doi.org/10.1128/MCB.01360-07.
47. Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, et al. Restoration of p53 function leads to tumour regression in vivo. Nature 2007; 445:661-5; PMID:17251932; http://dx.doi.org/10.1038/nature05541.
48. Wu CH, van Riggelen J, Yetil A, Fan AC, Bachireddy P, Felsher DW. Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc Natl Acad Sci USA 2007; 104:13028-33; PMID:17664422; http://dx.doi.org/10.1073/pnas.0701953104.
49. Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007; 445:656-60; PMID:17251933; http://dx.doi.org/10. 1038/nature05529.
50. Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 2006; 444:633-7; PMID:17136093; http://dx.doi.org/10.1038/nature05268.
51. Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, Liloglou T, et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 2005; 434:907-13; PMID:15829965; http://dx.doi.org/10.1038/nature03485.
52. Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C, et al. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 2006; 444:638-42; PMID:17136094; http://dx.doi.org/10. 1038/nature05327.
53. Harada H, Nakagawa H, Oyama K, Takaoka M, Andl CD, Jacobmeier B, et al. Telomerase induces immortalization of human esophageal keratinocytes without p16INK4a inactivation. Mol Cancer Res 2003; 1:729-38; PMID:12939398.
54. Zhuang D, Mannava S, Grachtchouk V, Tang WH, Patil S, Wawrzyniak JA, et al. C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells. Oncogene 2008; 27:6623-34; PMID:18679422; http://dx.doi.org/10.1038/onc.2008.258.
55. Bansal R, Nikiforov MA. Pathways of oncogeneinduced senescence in human melanocytic cells. Cell Cycle 2010; 9:2782-8; PMID:20676024; http:// dx.doi.org/10.4161/cc.9.14.12251.
56. Denoyelle C, Abou-Rjaily G, Bezrookove V, Verhaegen M, Johnson TM, Fullen DR, et al. Anti-oncogenic role of the endoplasmic reticulum differentially activated by mutations in the MAPK pathway. Nat Cell Biol 2006; 8:1053-63; PMID:16964246; http://dx.doi.org/10.1038/ncb1471.
57. Haferkamp S, Tran SL, Becker TM, Scurr LL, Kefford RF, Rizos H. The relative contributions of the p53 and pRb pathways in oncogene-induced melanocyte senescence. Aging (Albany NY) 2009; 1:542-56; PMID:20157537.
58. Cipriano R, Kan CE, Graham J, Danielpour D, Stampfer M, Jackson MW. TGF-beta signaling engages an ATM-CHK2-p53-independent RAS-induced senescence and prevents malignant transformation in human mammary epithelial cells. Proc Natl Acad Sci USA 2011; 108:8668-73; PMID:21555587; http://dx.doi.org/10.1073/ pnas.1015022108.
59. Demidenko ZN, Korotchkina LG, Gudkov AV, Blagosklonny MV. Paradoxical suppression of cellular senescence by p53. Proc Natl Acad Sci USA 2010; 107:9660-4; PMID:20457898; http://dx.doi.org/10.1073/pnas.1002298107.
60. Korotchkina LG, Leontieva OV, Bukreeva EI, Demidenko ZN, Gudkov AV, Blagosklonny MV. The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway. Aging (Albany NY) 2010; 2:344-52; PMID:20606252.
61. Schug TT. mTOR favors senescence over quiescence in p53-arrested cells. Aging (Albany NY) 2010; 2:327-8; PMID:20603524.
62. Maki CG. Decision-making by p53 and mTOR. Aging (Albany NY) 2010; 2:324-6; PMID:20603526.
63. Darzynkiewicz Z. Another "Janus paradox" of p53: induction of cell senescence versus quiescence. Aging (Albany NY) 2010; 2:329-30; PMID:20603525.
64. Drayton S, Rowe J, Jones R, Vatcheva R, Cuthbert-Heavens D, Marshall J, et al. Tumor suppressor p16INK4a determines sensitivity of human cells to transformation by cooperating cellular oncogenes. Cancer Cell 2003; 4:301-10; PMID:14585357; http://dx.doi.org/10.1016/S1535-6108(03)00242-3.
65. Benanti JA, Galloway DA. Normal human fibroblasts are resistant to RAS-induced senescence. Mol Cell Biol 2004; 24:2842-52; PMID:15024073; http://dx.doi.org/10.1128/MCB.24.7.2842-2852.2004.
66. Michaloglou C, Vredeveld LC, Soengas MS, Denoyelle C, Kuilman T, van der Horst CM, et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 2005; 436:720-4; PMID:16079850; http://dx.doi.org/10.1038/ nature03890.
67. Lee AC, Fenster BE, Ito H, Takeda K, Bae NS, Hirai T, et al. Ras proteins induce senescence by altering the intracellular levels of reactive oxygen species. J Biol Chem 1999; 274:7936-40; PMID:10075689; http://dx.doi.org/10. 1074/jbc.274.12.7936.
68. Xiao Z, Chen Z, Gunasekera AH, Sowin TJ, Rosenberg SH, Fesik S, et al. Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA damaging agents. J Biol Chem 2003; 278:21767-73; PMID:12676925; http://dx.doi.org/10.1074/jbc.M300229200.
69. Derheimer FA, Kastan MB. Multiple roles of ATM in monitoring and maintaining DNA integrity. FEBS Lett 2010; 584:3675-81; PMID:20580718; http://dx.doi.org/10.1016/j.febslet.2010.05.031.
70. Bakkenist CJ, Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 2003; 421:499-506; PMID:12556884; http://dx.doi.org/10.1038/nature01368.
71. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 1998; 273:5858-68; PMID:9488723; http://dx.doi.org/10.1074/jbc.273.10.5858.
72. Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 2001; 276:42462-7; PMID:11571274; http://dx.doi.org/10.1074/jbc.C100466200.
73. Kastan MB, Lim DS, Kim ST, Xu B, Canman C. Multiple signaling pathways involving ATM. Cold Spring Harb Symp Quant Biol 2000; 65:521-6; PMID:12760069; http://dx.doi.org/10.1101/sqb.2000.65.521.
74. Kastan MB, Lim DS. The many substrates and functions of ATM. Nat Rev Mol Cell Biol 2000; 1:179-86; PMID:11252893; http://dx.doi.org/10.1038/35043058.
75. Lim DS, Kim ST, Xu B, Maser RS, Lin J, Petrini JH, et al. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature 2000; 404:613-7; PMID:10766245; http://dx.doi.org/10.1038/35007091.
76. Garg R, Callens S, Lim DS, Canman CE, Kastan MB, Xu B. Chromatin association of rad17 is required for an ataxia telangiectasia and rad-related kinase-mediated S-phase checkpoint in response to low-dose ultraviolet radiation. Mol Cancer Res 2004; 2:362-9; PMID:15235112.
77. Bartkova J, Horejsí Z, Koed K, Krämer A, Tort F, Zieger K, et al. DNA damage response as a candidate anticancer barrier in early human tumorigenesis. Nature 2005; 434:864-70; PMID:15829956; http://dx.doi.org/10. 1038/nature03482.
78. Mallette FA, Ferbeyre G. The DNA damage signaling pathway connects oncogenic stress to cellular senescence. Cell Cycle 2007; 6:1831-6; PMID:17671427; http://dx.doi.org/10.4161/cc.6.15.4516.
79. Mannava S, Moparthy K, Wheeler L, Natarajan V, Zucker S, Fink E, et al. Depletion of deoxyribonucleotide pools is an endogenous source of DNA damage in cells undergoing oncogene-induced senescence. Am J Pathol 2012; In press.
80. Mannava S, Moparthy K, Wheeler L, Leonova K, Wawrzyniak J, Bianchi-Smiraglia A, et al. Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence-associated phenotypes caused by C-MYC depletion. Aging (Albany, NY Online) 2012; In press.
81. Pospelova TV, Demidenko ZN, Bukreeva EI, Pospelov VA, Gudkov AV, Blagosklonny MV. Pseudo-DNA damage response in senescent cells. Cell Cycle 2009; 8:4112-8; PMID:19946210; http://dx.doi.org/10.4161/cc.8.24.10215.
82. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004; 18:1926-45; PMID:15314020; http://dx.doi.org/10.1101/gad.1212704.
83. Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell 2000; 103:253-62; PMID:11057898; http://dx.doi.org/10.1016/S0092-8674(00)00117- 3.
84. Sarbassov DD, Ali SM, Sabatini DM. Growing roles for the mTOR pathway. Curr Opin Cell Biol 2005; 17:596-603; PMID:16226444; http://dx.doi.org/10.1016/ j.ceb.2005.09.009.
85. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell 2006; 124:471-84; PMID:16469695; http://dx.doi.org/10.1016/j. cell.2006.01.016.
86. Blagosklonny MV. Molecular damage in cancer: an argument for mTOR-driven aging. Aging (Albany NY) 2011; 3:1130-41; PMID:22246147.
87. Chappell WH, Steelman LS, Long JM, Kempf RC, Abrams SL, Franklin RA, et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health. Oncotarget 2011; 2:135-64; PMID:21411864.
88. Pani G. P66SHC and ageing: ROS and TOR? Aging (Albany NY) 2010; 2:514-8; PMID:20689155.
89. Zhao C, Vollrath D. mTOR pathway activation in age-related retinal disease. Aging (Albany NY) 2011; 3:346-7; PMID:21483039.
90. Blagosklonny MV. Hormesis does not make sense except in the light of TOR-driven aging. Aging (Albany NY) 2011; 3:1051-62; PMID:22166724.
91. Pospelova TV, Leontieva OV, Bykova TV, Zubova SG, Pospelov VA, Blagosklonny MV. Suppression of replicative senescence by rapamycin in rodent embryonic cells. Cell Cycle 2012; 11:2402-7; PMID:22672902; http://dx.doi.org/ 10.4161/cc.20882.
92. Blagosklonny MV. Cell cycle arrest is not senescence. Aging (Albany NY) 2011; 3:94-101; PMID:21297220.
93. Leontieva OV, Blagosklonny MV. DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence. Aging (Albany NY) 2010; 2:924-35; PMID:21212465.
94. Wesierska-Gadek J. mTOR and its link to the picture of Dorian Gray - re-activation of mTOR promotes aging. Aging (Albany NY) 2010; 2:892-3; PMID:21149896.
95. Soutoglou E, Misteli T. Activation of the cellular DNA damage response in the absence of DNA lesions. Science 2008; 320:1507-10; PMID:18483401; http://dx.doi.org/10.1126/science.1159051.
96. Bencokova Z, Kaufmann MR, Pires IM, Lecane PS, Giaccia AJ, Hammond EM. ATM activation and signaling under hypoxic conditions. Mol Cell Biol 2009; 29:526-37; PMID:18981219; http://dx.doi.org/10.1128/MCB.01301-08.
97. Gray-Schopfer V, Wellbrock C, Marais R. Melanoma biology and new targeted therapy. Nature 2007; 445:851-7; PMID:17314971; http://dx.doi.org/10.1038/ nature05661.
98. Gray-Schopfer VC, Karasarides M, Hayward R, Marais R. Tumor necrosis factor-alpha blocks apoptosis in melanoma cells when BRAF signaling is inhibited. Cancer Res 2007; 67:122-9; PMID:17210691; http://dx.doi.org/10.1158/ 0008-5472.CAN-06-1880.
99. Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, et al. High frequency of BRAF mutations in nevi. Nat Genet 2003; 33:19-20; PMID:12447372; http://dx.doi.org/10.1038/ng1054.
100. Pollock PM, Meltzer PS. A genome-based strategy uncovers frequent BRAF mutations in melanoma. Cancer Cell 2002; 2:5-7; PMID:12150818; http://dx.doi.org/10.1016/S1535-6108(02)00089-2.
101. Da Forno PD, Pringle JH, Fletcher A, Bamford M, Su L, Potter L, et al. BRAF, NRAS and HRAS mutations in spitzoid tumours and their possible pathogenetic significance. Br J Dermatol 2009; 161:364-72; PMID:19438459; http://dx.doi.org/10.1111/j.1365-2133.2009.09181.x.
102. Ross AL, Sanchez MI, Grichnik JM. Molecular nevogenesis. Dermatol Res Pract 2011; 2011:463184; PMID:21754924; http://dx.doi.org/10.1155/2011/463184.
103. Bauer J, Curtin JA, Pinkel D, Bastian BC. Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol 2007; 127:179-82; PMID:16888631; http://dx.doi.org/10.1038/sj.jid.5700490.
104. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 2005; 353:2135-47; PMID:16291983; http://dx.doi.org/10.1056/NEJMoa050092.
105. Maldonado JL, Fridlyand J, Patel H, Jain AN, Busam K, Kageshita T, et al. Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst 2003; 95:1878-90; PMID:14679157; http://dx.doi.org/10.1093/jnci/djg123.
106. Mannava S, Omilian AR, Wawrzyniak JA, Fink EE, Zhuang D, Miecznikowski JC, et al. PP2AB56α controls oncogene-induced senescence in normal and tumor human melanocytic cells. Oncogene 2012; 31:1484-92; PMID:21822300; http://dx.doi.org/10.1038/onc.2011.339.
107. Wang S, Kaufman RJ. The impact of the unfolded protein response on human disease. J Cell Biol 2012; 197:857-67; PMID:22733998; http://dx.doi.org/10.1083/ jcb.201110131.