Exploiting cellular senescence to treat cancer and circumvent drug resistance

Cancer Biology and Therapy

Volumn 9, Issue 3, 2010, Pages 166-175

  Yan, Qin ^a   Wajapeyee, Narendra ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Drug resistance; Oncogene; p53; RB; RNAi; Senescence; Telomere

Indexed keywords

ANTINEOPLASTIC AGENT; GEMCITABINE; GV 1001; MICRORNA; PROTEIN P53; RETINOBLASTOMA PROTEIN; TELOMERASE; UNCLASSIFIED DRUG;

AUTOPHAGY; CANCER RECURRENCE; CANCER THERAPY; CELL AGING; CELL DIVISION; DNA DAMAGE; GENOMICS; HIGH THROUGHPUT SCREENING; HUMAN; METASTASIS; ONCOGENE; PANCREAS CANCER; PROTEIN SECRETION; REGULATORY MECHANISM; REVIEW; TELOMERE;

ANIMALS; CELL AGING; DRUG RESISTANCE, NEOPLASM; HUMANS; NEOPLASMS;

EID: 77953567284     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.9.3.11166     Document Type: Review

References (96)

1. Campisi J, d'Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev 2007; 8:729-40.
2. Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res 1961; 25:585-621.
3. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Nat Acad Sci USA 1995; 92:9363-7.
4. INK4a. Cell 1997; 88:593-602.
5. Narita M, Krizhanovsky V, Nunez S, Chicas A, Hearn SA, Myers MP, et al. A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell 2006; 126:503-14. (Pubitemid 44163608)
6. 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. (Pubitemid 41117276)
7. Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature 1990; 345:458-60.
8. Wei S, Sedivy JM. Expression of catalytically active telomerase does not prevent premature senescence caused by overexpression of oncogenic Ha-Ras in normal human fibroblasts. Cancer Res 1999; 59:1539-43. (Pubitemid 29160123)
9. Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, et al. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 2005; 436:660-5.
10. Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, Barradas M, et al. Tumour biology: senescence in premalignant tumours. Nature 2005; 436:642.
11. Majumder PK, Grisanzio C, O'Connell F, Barry M, Brito JM, Xu Q, et al. A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression. Cancer Cell 2008; 14:146-55.
12. Roberson RS, Kussick SJ, Vallieres E, Chen SY, Wu DY. Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers. Cancer Res 2005; 65:2795-803.
13. te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP. DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res 2002; 62:1876-83.
14. Blackburn EH. Switching and signaling at the telomere. Cell 2001; 106:661-73.
15. Allshire RC, Dempster M, Hastie ND. Human telomeres contain at least three types of G-rich repeat distributed non-randomly. Nucleic Acids Res 1989; 17:4611-27. (Pubitemid 19165034)
16. Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet 2008; 42:301-34.
17. Blasco MA. The epigenetic regulation of mammalian telomeres. Nat Rev Genet 2007; 8:299-309.
18. Lundblad V, Blackburn EH. An alternative pathway for yeast telomere maintenance rescues est1-senescence. Cell 1993; 73:347-60. (Pubitemid 23123312)
19. Lingner J, Hughes TR, Shevchenko A, Mann M, Lundblad V, Cech TR. Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 1997; 276:561-7. (Pubitemid 27193675)
20. Meyerson M, Counter CM, Eaton EN, Ellisen LW, Steiner P, Caddle SD, et al. hEST2, the putative human telomerase catalytic subunit gene, is upregulated in tumor cells and during immortalization. Cell 1997; 90:785-95.
21. Greider CW, Blackburn EH. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature 1989; 337:331-7.
22. Shippen-Lentz D, Blackburn EH. Functional evidence for an RNA template in telomerase. Science 1990; 247:546-52. (Pubitemid 120031333)
23. Smogorzewska A, de Lange T. Regulation of telomerase by telomeric proteins. Annu Rev Biochem 2004; 73:177-208.
24. Armanios M. Syndromes of telomere shortening. Annu Rev Genomics Hum Genet 2009; 10:45-61.
25. Dunham MA, Neumann AA, Fasching CL, Reddel RR. Telomere maintenance by recombination in human cells. Nat Genet 2000; 26:447-50.
26. Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR. Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J 1995; 14:4240-8.
27. Muntoni A, Reddel RR. The first molecular details of ALT in human tumor cells. Hum Mol Genet 2005; 14:191-6.
28. Cesare AJ, Reddel RR. Telomere uncapping and alternative lengthening of telomeres. Mech Ageing Dev 2008; 129:99-108.
29. Denchi EL, de Lange T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 2007; 448:1068-71.
30. Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 1999; 283:1321-5.
31. van Steensel B, Smogorzewska A, de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell 1998; 92:401-13. (Pubitemid 28093017)
32. Gire V, Roux P, Wynford-Thomas D, Brondello JM, Dulic V. DNA damage checkpoint kinase Chk2 triggers replicative senescence. EMBO J 2004; 23:2554-63. (Pubitemid 38988227)
33. Roos WP, Kaina B. DNA damage-induced cell death by apoptosis. Trends Mol Med 2006; 12:440-50.
34. Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell 2007; 130:223-33.
35. d'Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003; 426:194-8.
36. Takai H, Smogorzewska A, de Lange T. DNA damage foci at dysfunctional telomeres. Curr Biol 2003; 13:1549-56. (Pubitemid 37078413)
37. Herbig U, Jobling WA, Chen BP, Chen DJ, Sedivy JM. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53 and p21(CIP1), but not p16(INK4a). Mol Cell 2004; 14:501-13.
38. Herbig U, Sedivy JM. Regulation of growth arrest in senescence: telomere damage is not the end of the story. Mech Ageing Dev 2006; 127:16-24. (Pubitemid 41713510)
39. Narita M, Nunez S, Heard E, Lin AW, Hearn SA, Spector DL, et al. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 2003; 113:703-16. (Pubitemid 36724935)
40. Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, et al. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J 2003; 22:4212-22.
41. Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 1997; 91:25-34.
42. Lee HW, Blasco MA, Gottlieb GJ, Horner JW, 2nd, Greider CW, DePinho RA. Essential role of mouse telomerase in highly proliferative organs. Nature 1998; 392:569-74.
43. Tomas-Loba A, Flores I, Fernandez-Marcos PJ, Cayuela ML, Maraver A, Tejera A, et al. Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 2008; 135:609-22.
44. Harley CB. Telomerase and cancer therapeutics. Nat Rev Cancer 2008; 8:167-79.
45. Buanes T, Maurel J, Liauw W, Hebbar M, Memunaitis J. A randomized phase III study of gemcitabine (G) versus GV1001 in sequential combination with G in patients with unresectable and metastatic pancreatic cancer (PC). J Clin Oncol 2009; 27.
46. Cong Y, Shay JW. Actions of human telomerase beyond telomeres. Cell Res 2008; 18:725-32.
47. Maida Y, Yasukawa M, Furuuchi M, Lassmann T, Possemato R, Okamoto N, et al. An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature 2009; 461:230-5.
48. Shay JW, Wright WE. Telomerase therapeutics for cancer: challenges and new directions. Nat Rev Drug Discov 2006; 5:577-84.
49. Herbert BS, Gellert GC, Hochreiter A, Pongracz K, Wright WE, Zielinska D, et al. Lipid modification of GRN163, an N3′→P5′ thio-phosphoramidate oligonucleotide, enhances the potency of telomerase inhibition. Oncogene 2005; 24:5262-8.
50. Dikmen ZG, Ozgurtas T, Gryaznov SM, Herbert BS. Targeting critical steps of cancer metastasis and recurrence using telomerase template antagonists. Biochim Biophys Acta 2009; 1792:240-7.
51. Salvati E, Leonetti C, Rizzo A, Scarsella M, Mottolese M, Galati R, et al. Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect. J Clin Invest 2007; 117:3236-47.
52. Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 1989; 244:217-21.
53. Oren M. Decision making by p53: life, death and cancer. Cell Death Differ 2003; 10:431-42. (Pubitemid 36626355)
54. Weinberg RA. The retinoblastoma gene and cell growth control. Trends Biochem Sci 1990; 15:199-202. (Pubitemid 20190929)
55. Zhu J, Woods D, McMahon M, Bishop JM. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev 1998; 12:2997-3007. (Pubitemid 28469302)
56. Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 2008; 132:363-74. (Pubitemid 351191995)
57. Yu H, McDaid R, Lee J, Possik P, Li L, Kumar SM, et al. The role of BRAF mutation and p53 inactivation during transformation of a subpopulation of primary human melanocytes. Am J Pathol 2009; 174:2367-77.
58. Polsky D, Bastian BC, Hazan C, Melzer K, Pack J, Houghton A, et al. HDM2 protein overexpression, but not gene amplification, is related to tumorigenesis of cutaneous melanoma. Cancer Res 2001; 61:7642-6. (Pubitemid 32995060)
59. Wang W, El-Deiry WS. Restoration of p53 to limit tumor growth. Curr Opin Oncol 2008; 20:90-6.
60. Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, et al. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev 2007; 21:525-30.
61. Kia SK, Gorski MM, Giannakopoulos S, Verrijzer CP. SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus. Mol Cell Biol 2008; 28:3457-64.
62. Agger K, Cloos PA, Rudkjaer L, Williams K, Andersen G, Christensen J, et al. The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence. Genes Dev 2009; 23:1171-6.
63. Barradas M, Anderton E, Acosta JC, Li S, Banito A, Rodriguez-Niedenfuhr M, et al. Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS. Genes Dev 2009; 23:1177-82.
64. Pfau R, Tzatsos A, Kampranis SC, Serebrennikova OB, Bear SE, Tsichlis PN. Members of a family of JmjC domain-containing oncoproteins immortalize embryonic fibroblasts via a JmjC domain-dependent process. Proc Nat Acad Sci USA 2008; 105:1907-12.
65. He J, Kallin EM, Tsukada Y, Zhang Y. The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15(Ink4b). Nat Struct Mol Biol 2008; 15:1169-75.
66. Tzatsos A, Pfau R, Kampranis SC, Tsichlis PN. Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus. Proc Nat Acad Sci USA 2009; 106:2641-6.
67. Benevolenskaya EV, Murray HL, Branton P, Young RA, Kaelin WG Jr. Binding of pRB to the PHD protein RBP2 promotes cellular differentiation. Mol Cell 2005; 18:623-35. (Pubitemid 40804799)
68. Zeng J, Ge Z, Wang L, Li Q, Wang N, Bjorkholm M, et al. The histone demethylase RBP2 is overexpressed in gastric cancer and its inhibition triggers senescence of cancer cells. Gastroenterology 2009.
69. 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.
70. 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.
71. Efeyan A, Murga M, Martinez-Pastor B, Ortega-Molina A, Soria R, Collado M, et al. Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression. PLoS One 2009; 4:5475.
72. Viale A, De Franco F, Orleth A, Cambiaghi V, Giuliani V, Bossi D, et al. Cell cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells. Nature 2009; 457:51-6.
73. Kuilman T, Peeper DS. Senescence-messaging secretome: SMS-ing cellular stress. Nat Rev Cancer 2009; 9:81-94.
74. Acosta JC, O'Loghlen A, Banito A, Guijarro MV, Augert A, Raguz S, et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 2008; 133:1006-18.
75. Kuilman T, Michaloglou C, Vredeveld LC, Douma S, van Doorn R, Desmet CJ, et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 2008; 133:1019-31. (Pubitemid 351787746)
76. Coppe JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008; 6:2853-68.
77. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008; 451:1069-75. (Pubitemid 351317450)
78. Young AR, Narita M, Ferreira M, Kirschner K, Sadaie M, Darot JF, et al. Autophagy mediates the mitotic senescence transition. Genes Dev 2009; 23:798-803.
79. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004; 5:522-31. (Pubitemid 38868508)
80. He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature 2007; 447:1130-4.
81. Malone CD, Hannon GJ. Small RNAs as guardians of the genome. Cell 2009; 136:656-68.
82. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Nat Acad Sci USA 2004; 101:2999-3004. (Pubitemid 38327724)
83. Cahill S, Smyth P, Denning K, Flavin R, Li J, Potratz A, et al. Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model. Mol Cancer 2007; 6:21. (Pubitemid 46488208)
84. Bhaumik D, Scott GK, Schokrpur S, Patil CK, Orjalo A, Rodier F, et al. MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8. Aging 2009; 1:402-11.
85. Chi SW, Zang JB, Mele A, Darnell RB. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 2009; 460:479-86.
86. Luo J, Emanuele MJ, Li D, Creighton CJ, Schlabach MR, Westbrook TF, et al. A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 2009; 137:835-48.
87. Scholl C, Frohling S, Dunn IF, Schinzel AC, Barbie DA, Kim SY, et al. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell 2009; 137:821-34.
88. Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF, et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 2009; 462:108-12.
89. Krizhanovsky V, Yon M, Dickins RA, Hearn S, Simon J, Miething C, et al. Senescence of activated stellate cells limits liver fibrosis. Cell 2008; 134:657-67.
90. Davis T, Haughton MF, Jones CJ, Kipling D. Prevention of accelerated cell aging in the Werner syndrome. Ann N Y Acad Sci 2006; 1067:243-7. (Pubitemid 43806331)
91. Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in dyskeratosis congenita. Blood 2009; 113:6549-57.
92. Hong H, Takahashi K, Ichisaka T, Aoi T, Kanagawa O, Nakagawa M, et al. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 2009; 460:1132-5.
93. Li H, Collado M, Villasante A, Strati K, Ortega S, Canamero M, et al. The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 2009; 460:1136-9.
94. Marion RM, Strati K, Li H, Murga M, Blanco R, Ortega S, et al. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 2009; 460:1149-53.
95. Utikal J, Polo JM, Stadtfeld M, Maherali N, Kulalert W, Walsh RM, et al. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 2009; 460:1145-8.
96. Kawamura T, Suzuki J, Wang YV, Menendez S, Morera LB, Raya A, et al. Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 2009; 460:1140-4.