DOI QR코드

DOI QR Code

Exploiting tumor cell senescence in anticancer therapy

  • Lee, Minyoung ;
  • Lee, Jae-Seon
  • Received : 2014.12.02
  • Published : 2014.02.28

Abstract

Cellular senescence is a physiological process of irreversible cell-cycle arrest that contributes to various physiological and pathological processes of aging. Whereas replicative senescence is associated with telomere attrition after repeated cell division, stress-induced premature senescence occurs in response to aberrant oncogenic signaling, oxidative stress, and DNA damage which is independent of telomere dysfunction. Recent evidence indicates that cellular senescence provides a barrier to tumorigenesis and is a determinant of the outcome of cancer treatment. However, the senescence-associated secretory phenotype, which contributes to multiple facets of senescent cancer cells, may influence both cancer-inhibitory and cancer-promoting mechanisms of neighboring cells. Conventional treatments, such as chemo- and radiotherapies, preferentially induce premature senescence instead of apoptosis in the appropriate cellular context. In addition, treatment-induced premature senescence could compensate for resistance to apoptosis via alternative signaling pathways. Therefore, we believe that an intensive effort to understand cancer cell senescence could facilitate the development of novel therapeutic strategies for improving the efficacy of anticancer therapies. This review summarizes the current understanding of molecular mechanisms, functions, and clinical applications of cellular senescence for anticancer therapy.

Keywords

Anticancer therapy;Cellular senescence;Tumorigenesis;SASP

References

  1. Chen, Z., Trotman, L. C., Shaffer, D., Lin, H. K., Dotan, Z. A., Niki, M., Koutcher, J. A., Scher, H. I., Ludwig, T., Gerald, W., Cordon-Cardo, C. and Pandolfi, P. P. (2005) Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436, 725-730. https://doi.org/10.1038/nature03918
  2. Efeyan, A., Ortega-Molina, A., Velasco-Miguel, S., Herranz, D., Vassilev, L. T. and Serrano, M. (2007) Induction of p53-dependent senescence by the MDM2 antagonist nutlin-3a in mouse cells of fibroblast origin. Cancer Res. 67, 7350-7357. https://doi.org/10.1158/0008-5472.CAN-07-0200
  3. Campisi, J. (1996) Replicative senescence: an old lives' tale? Cell 84, 497-500. https://doi.org/10.1016/S0092-8674(00)81023-5
  4. Deng, Y. and Chang, S. (2007) Role of telomeres and telomerase in genomic instability, senescence and cancer. Lab. Invest. 87, 1071-1076. https://doi.org/10.1038/labinvest.3700673
  5. Toussaint, O., Medrano, E. E. and von Zglinicki, T. (2000) Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp. Gerontol. 35, 927-945. https://doi.org/10.1016/S0531-5565(00)00180-7
  6. Gorgoulis, V. G. and Halazonetis, T. D. (2010) Oncogene-induced senescence: the bright and dark side of the response. Curr. Opin. Cell. Biol. 22, 816-827. https://doi.org/10.1016/j.ceb.2010.07.013
  7. Ben-Porath, I. and Weinberg, R. A. (2005) The signals and pathways activating cellular senescence. Int. J. Biochem. Cell. Biol. 37, 961-976. https://doi.org/10.1016/j.biocel.2004.10.013
  8. Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D. and Lowe, S. W. (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593-602. https://doi.org/10.1016/S0092-8674(00)81902-9
  9. Young, A. P., Schlisio, S., Minamishima, Y. A., Zhang, Q., Li, L., Grisanzio, C., Signoretti, S. and Kaelin, W. G. Jr. (2008) VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat. Cell Biol. 10, 361-369. https://doi.org/10.1038/ncb1699
  10. Shamma, A., Takegami, Y., Miki, T., Kitajima, S., Noda, M., Obara, T., Okamoto, T. and Takahashi, C. (2009) Rb Regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation. Cancer Cell 15, 255-269. https://doi.org/10.1016/j.ccr.2009.03.001
  11. Suzuki, M. and Boothman, D. A. (2008) Stress-induced premature senescence (SIPS)--influence of SIPS on radiotherapy. J. Radiat. Res. 49, 105-112. https://doi.org/10.1269/jrr.07081
  12. Young, A. R. and Narita, M. (2009) SASP reflects senescence. EMBO Rep. 10, 228-230. https://doi.org/10.1038/embor.2009.22
  13. Gewirtz, D. A., Holt, S. E. and Elmore, L. W. (2008) Accelerated senescence: an emerging role in tumor cell response to chemotherapy and radiation. Biochem. Pharmacol. 76, 947-957. https://doi.org/10.1016/j.bcp.2008.06.024
  14. Davalos, A. R., Coppe, J. P., Campisi, J. and Desprez, P. Y. (2010) Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis. Rev. 29, 273-283. https://doi.org/10.1007/s10555-010-9220-9
  15. Campisi, J., Andersen, J. K., Kapahi, P. and Melov, S. (2011) Cellular senescence: a link between cancer and age-related degenerative disease? Semin. Cancer Biol. 21, 354-359.
  16. Coppe, J. P., Desprez, P. Y., Krtolica, A. and Campisi, J. (2010) The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99-118. https://doi.org/10.1146/annurev-pathol-121808-102144
  17. Campisi, J. (2013) Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 75, 685-705. https://doi.org/10.1146/annurev-physiol-030212-183653
  18. de Magalhaes, J. P. (2013) How ageing processes influence cancer. Nat. Rev. Cancer 13, 357-365. https://doi.org/10.1038/nrc3497
  19. Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M. and Kroemer, G. (2013) The hallmarks of aging. Cell 153, 1194-1217. https://doi.org/10.1016/j.cell.2013.05.039
  20. Oyama, K., Okawa, T., Nakagawa, H., Takaoka, M., Andl, C. D., Kim, S. H., Klein-Szanto, A., Diehl, J. A., Herlyn, M., El-Deiry, W. and Rustgi, A. K. (2007) AKT induces senescence in primary esophageal epithelial cells but is permissive for differentiation as revealed in organotypic culture. Oncogene 26, 2353-2364. https://doi.org/10.1038/sj.onc.1210025
  21. Dhomen, N., Reis-Filho, J. S., da Rocha Dias, S., Hayward, R., Savage, K., Delmas, V., Larue, L., Pritchard, C. and Marais, R. (2009) Oncogenic Braf induces melanocyte senescene and melanoma in mice. Cancer Cell 15, 294-303. https://doi.org/10.1016/j.ccr.2009.02.022
  22. Collado, M., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguria, A., Zaballos, A., Flores, J. M., Barbacid, M., Beach, D. and Serrano, M. (2005) Tumor biology: senescence in premalignant tumors. Nature 436, 642. https://doi.org/10.1038/436642a
  23. Kuilman, T., Michaloglou, C., Mooi, W. J. and Peeper, D. S. (2010) The essence of senescence. Genes Dev. 24, 2463-2479. https://doi.org/10.1101/gad.1971610
  24. Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O., Peacocke, M. and Campisi, J. (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. U. S. A. 92, 9363-9367. https://doi.org/10.1073/pnas.92.20.9363
  25. Canpo-Trapero, J., Cano-Sanchez, J., Palacios-Sanchez, B., Llamas-Martinez, S., Lo Muzio, L. and Bascones-Martinez, A. (2008) Cellular senescence in oral cancer and precancer and treatment implications: A review. Acta. Oncologica. 47, 1464-1474. https://doi.org/10.1080/02841860802183612
  26. Byun, H. O., Han, N. K., Lee, H. J., Kim, K. B., Ko, Y. G., Yoon, G., Lee, Y. S., Hong, S. I. and Lee, J. S. (2009) Cathepsin D and eukaryotic translation elongation factor 1 as promising markers of cellular senescence. Cancer Res. 69, 4638-4647. https://doi.org/10.1158/0008-5472.CAN-08-4042
  27. de Magalhaes, J. P., Curado, J. and Church, G. M. (2009) Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics 25, 875-881. https://doi.org/10.1093/bioinformatics/btp073
  28. Mason, D. X., Jackson, T. J. and Lin, A. W. (2004) Molecular signature of oncogenic ras-induced senescence. Oncogene 23, 9238-9246. https://doi.org/10.1038/sj.onc.1208172
  29. Wennmalm, K., Wahlestedt, C. and Larsson, O. (2005) The expression signature of in vitro senescence resembles mouse but not human aging. Genome. Biol. 6, R109. https://doi.org/10.1186/gb-2005-6-13-r109
  30. Calvanese, V., Lara, E., Kahn, A. and Fraga, M. F. (2009) The role of epigenetics in aging and age-related diseases. Ageing. Res. Rev. 8, 268-276. https://doi.org/10.1016/j.arr.2009.03.004
  31. Larsson, L. G. (2011) Oncogene- and tumor suppressor gene-mediated suppression of cellular senescence. Semin. Cancer Biol. 21, 367-376.
  32. Ohtani, N. and Hara, E. (2013) Roles and mechanisms of cellular senescence in regulation of tissue homeostasis. Cancer Sci. 104, 525-530. https://doi.org/10.1111/cas.12118
  33. Adams, P. D. (2009) Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence. Mol. Cell 36, 2-14. https://doi.org/10.1016/j.molcel.2009.09.021
  34. Chandler, H. and Peters, G. (2013) Stressing the cell cycle in senescence and aging. Curr. Opin. Cell Biol. 25, 765-771. https://doi.org/10.1016/j.ceb.2013.07.005
  35. Reinhardt, H. C. and Schumacher, B. (2012) The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends. Genet. 28, 128-136. https://doi.org/10.1016/j.tig.2011.12.002
  36. Warfel, N. A. and El-Deiry, W. S. (2013) p21WAF1 and tumourigenesis: 20 years after. Curr. Opin. Oncol. 25, 52-58. https://doi.org/10.1097/CCO.0b013e32835b639e
  37. Roninson, I. B. (2002) Oncogenic functions of tumour suppressor p21(Waf1/Cip1/Sdi1): association with cell senescence and tumour-promoting activities of stromal fibroblasts. Cancer Lett. 179, 1-14. https://doi.org/10.1016/S0304-3835(01)00847-3
  38. Carnero, A. and Beach, D. H. (2004) Absence of p21WAF1 cooperates with c-myc in bypassing Ras-induced senescence and enhances oncogenic cooperation. Oncogene 23, 6006-6011. https://doi.org/10.1038/sj.onc.1207839
  39. Groth, A., Weber, J. D., Willumsen, B. M., Sherr, C. J. and Roussel, M. F. (2000) Oncogenic Ras induces p19ARF and growth arrest in mouse embryo fibroblasts lacking p21Cip1 and p27Kip1 without activating cyclin D-dependent kinases. J. Biol. Chem. 275, 27473-27480.
  40. Pantoja, C. and Serrano, M. (1999) Murine fibroblasts lacking p21 undergo senescence and are resistant to transformation by oncogenic Ras. Oncogene 18, 4974-4982. https://doi.org/10.1038/sj.onc.1202880
  41. Dominguez-Brauer, C., Brauer, P. M., Chen, Y. J., Pimkina, J. and Raychaudhuri, P. (2010) Tumor suppression by ARF: gatekeeper and caretaker. Cell Cycle. 9, 86-89. https://doi.org/10.4161/cc.9.1.10350
  42. Indovina, P., Marcelli, E., Casini, N., Rizzo, V. and Giordano, A. (2013) Emerging roles of RB family: new defense mechanisms against tumor progression. J. Cell Physiol. 228, 525-535. https://doi.org/10.1002/jcp.24170
  43. Kim, W. Y. and Sharpless, N. E. (2006) The regulation of INK4/ARF in cancer and aging. Cell 127, 265-275. https://doi.org/10.1016/j.cell.2006.10.003
  44. Rayess, H., Wang, M. B. and Srivatsan, E. S. (2012) Cellular senescence and tumor suppressor gene p16. Int. J. Cancer 130, 1715-1725. https://doi.org/10.1002/ijc.27316
  45. Wadhwa, R., Sugihara, T., Taira, K. and Kaul, S. C. (2004) The ARF-p53 senescence pathway in mouse and human cells. Histol. Histopathol. 19, 311-316.
  46. Parrinello, S., Coppe, J. P., Krtolica, A. and Campisi, J. (2005) Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. J. Cell Sci. 118, 485-496. https://doi.org/10.1242/jcs.01635
  47. Salminen, A., Kauppinen, A. and Kaarniranta, K. (2012) Emerging role of NF-kappaB signaling in the induction of senescence-associated secretory phenotype (SASP). Cell Signal. 24, 835-845. https://doi.org/10.1016/j.cellsig.2011.12.006
  48. Coppe, J. P., Kauser, K., Campisi, J. and Beausejour, C. M. (2006) Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence. J. Biol. Chem. 281, 29568-29574. https://doi.org/10.1074/jbc.M603307200
  49. Gosselin, K., Martien, S., Pourtier, A., Vercamer, C., Ostoich, P., Morat, L., Sabatier, L., Duprez, L., T'Kint de Roodenbeke, C., Gilson, E., Malaquin, N., Wernert, N., Slijepcevic, P., Ashtari, M., Chelli, F., Deruy, E., Vandenbunder, B., De Launoit, Y. and Abbadie, C. (2009) Senescence-associated oxidative DNA damage promotes the generation of neoplastic cells. Cancer Res. 69, 7917-7925. https://doi.org/10.1158/0008-5472.CAN-08-2510
  50. Acosta, J. C., O'Loghlen, A., Banito, A., Raguz, S. and Gil, J. (2008) Control of senescence by CXCR2 and its ligands. Cell Cycle 7, 2956-2959. https://doi.org/10.4161/cc.7.19.6780
  51. Bavik, C., Coleman, I., Dean, J. P., Knudsen, B., Plymate, S. and Nelson, P. S. (2006) The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms. Cancer Res. 66, 794-802. https://doi.org/10.1158/0008-5472.CAN-05-1716
  52. Pazolli, E., Luo, X., Brehm, S., Carbery, K., Chung, J. J., Prior, J. L., Doherty, J., Demehri, S., Salavaggione, L., Piwnica-Worms, D. and Stewart, S. A. (2009) Senescent stromal-derived osteopontin promotes preneoplastic cell growth. Cancer Res. 69, 1230-1239. https://doi.org/10.1158/0008-5472.CAN-08-2970
  53. Sagiv, A. and Krizhanovsky, V. (2013) Immunosurveillance of senescent cells: the bright side of the senescence program. Biogerontology. 14, 617-628. https://doi.org/10.1007/s10522-013-9473-0
  54. Mariotti, M., Castiglioni, S., Bernardini, D. and Maier, J. A. (2006) Interleukin 1 alpha is a marker of endothelial cellular senescent. Immun. Ageing 3, 4. https://doi.org/10.1186/1742-4933-3-4
  55. Orjalo, A. V., Bhaumik, D., Gengler, B. K., Scott, G. K. and Campisi, J. (2009) Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proc. Natl. Acad. Sci. U. S. A. 106, 17031-17036. https://doi.org/10.1073/pnas.0905299106
  56. Novakova, Z., Hubackova, S., Kosar, M., Janderova- Rossmeislova, L., Dobrovolna, J., Vasicova, P., Vancurova, M., Horejsi, Z., Hozak, P., Bartek, J. and Hodny, Z. (2010) Cytokine expression and signaling in drug-induced cellular senescence. Oncogene 29, 273-284. https://doi.org/10.1038/onc.2009.318
  57. Coppe, J. P., Patil, C. K., Rodier, F., Sun, Y., Munoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P. Y. and Campisi, J. (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, 2853-2868.
  58. Puche, J. E. and Castilla-Cortazar, I. (2012) Human conditions of insulin-like growth factor-I (IGF-I) deficiency. J. Transl. Med. 10, 224. https://doi.org/10.1186/1479-5876-10-224
  59. Lopez-Bermejo, A., Buckway, C. K., Devi, G. R., Hwa, V., Plymate, S. R., Oh, Y. and Rosenfeld, R. G. (2000) Characterization of insulin-like growth factor-binding protein-related proteins (IGFBP-rPs) 1, 2, and 3 in human prostate epithelial cells: potential roles for IGFBP-rP1 and 2 in senescence of the prostatic epithelium. Endocrinology 141, 4072-4080. https://doi.org/10.1210/endo.141.11.7783
  60. Maki, R. G. (2010) Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer. J. Clin. Oncol. 28, 4985-4995. https://doi.org/10.1200/JCO.2009.27.5040
  61. Wang, S., Moerman, E. J., Jones, R. A., Thweatt, R. and Goldstein, S. (1996) Characterization of IGFBP-3, PAI-1 and SPARC mRNA expression in senescent fibroblasts. Mech. Ageing. Dev. 92, 121-132. https://doi.org/10.1016/S0047-6374(96)01814-3
  62. Liu, D. and Hornsby, P. J. (2007) Senescent human fibroblasts increase the early growth of xenograft tumors via matrix metalloproteinase secretion. Cancer Res. 67, 3117-3126. https://doi.org/10.1158/0008-5472.CAN-06-3452
  63. Tsai, K. K., Chuang, E. Y., Little, J. B. and Yuan, Z. M. (2005) Cellular mechanisms for low-dose ionizing radiation- induced perturbation of the breast tissue microenvironment. Cancer Res. 65, 6734-6744. https://doi.org/10.1158/0008-5472.CAN-05-0703
  64. Dass, K., Ahmad, A., Azmi, A. S., Sarkar, S. H. and Sarkar, F. H. (2008) Evolving role of uPA/uPAR system in human cancers. Cancer Treat. Rev. 34, 122-136. https://doi.org/10.1016/j.ctrv.2007.10.005
  65. Barcellos-Hoff, M. H. and Ravani, S. A. (2000) Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells. Cancer Res. 60, 1254-1260.
  66. Hornebeck, W. and Maquart, F. X. (2003) Proteolyzed matrix as a template for the regulation of tumor progression. Biomed. Pharmacother. 57, 223-230. https://doi.org/10.1016/S0753-3322(03)00049-0
  67. Schadendorf, D., Moller, A., Algermissen, B., Worm, M., Sticherling, M. and Czarnetzki, B. M. (1993) IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. J. Immunol. 151, 2667-2675.
  68. Norgauer, J., Metzner, B. and Schraufstatter, I. (1996) Expression and growth-promoting function of the IL-8 receptor beta in human melanoma cells. J. Immunol. 156, 1132-1137.
  69. Ksiazek, K., Jorres, A. and Witowski, J. (2008) Senescence induces a proangiogenic switch in human peritoneal mesothelial cells. Rejuvenation. Res. 11, 681-683. https://doi.org/10.1089/rej.2008.0736
  70. Chaturvedi, S. and Hass, R. (2011) Extracellular signals in young and aging breast epithelial cells and possible connections to age-associated breast cancer development. Mech. Ageing. Dev. 132, 213-219. https://doi.org/10.1016/j.mad.2011.04.002
  71. Studebaker, A. W., Storci, G., Werbeck, J. L., Sansone, P., Sasser, A. K., Tavolari, S., Huang, T., Chan, M. W., Marini, F. C., Rosol, T. J., Bonafe, M. and Hall, B. M. (2008) Fibroblasts isolated from common sites of breast cancer metastasis enhance cancer cell growth rates and invasiveness in an interleukin-6-dependent manner. Cancer Res. 68, 9087-9095. https://doi.org/10.1158/0008-5472.CAN-08-0400
  72. Laberge, R. M., Awad, P., Campisi, J. and Desprez, P. Y. (2012) Epithelial-mesenchymal transition induced by senescent fibroblasts. Cancer Microenviron. 5, 39-44. https://doi.org/10.1007/s12307-011-0069-4
  73. Smit, M. A. and Peeper, D. S. (2010) Epithelial-mesenchymal transition and senescence: two cancer-related processes are crossing paths. Aging (Albany NY) 2, 735-741.
  74. Sica, A., Schioppa, T., Mantovani, A. and Allavena, P. (2006) Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur. J. Cancer 42, 717-727. https://doi.org/10.1016/j.ejca.2006.01.003
  75. Han, N. K., Kim, B. C., Lee, H. C., Lee, Y. J., Park, M. J., Chi, S. G., Ko, Y. G. and Lee, J. S. (2012) Secretome analysis of ionizing radiation-induced senescent cancer cells reveals that secreted RKIP plays a critical role in neighboring cell migration. Proteomics 12, 2822-2832. https://doi.org/10.1002/pmic.201100419
  76. Xue, W., Zender, L., Miethng, C., Dickins R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C. and Lowe, S. M. (2007) Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656-660. https://doi.org/10.1038/nature05529
  77. Kang, T. W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., Iken, M., Vucur, M., Weiss, S., Heikenwalder, M., Khan, S., Gil, J., Bruder, D., Manns, M., Schirmacher, P., Tacke, F., Ott, M., Luedde, T., Longerich, T., Kubicka, S. and Zender, L. (2011) Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 479, 547-551. https://doi.org/10.1038/nature10599
  78. Nardella, C., Clohessy, J. G., Alimonti, A. and Pandolfi, P. P. (2011) Pro-senescence therapy for cancer treatment. Nat. Rev. Cancer 11, 503-511. https://doi.org/10.1038/nrc3057
  79. Acosta, J. C. and Gil, J. (2012) Senescence: a new weapon for cancer therapy. Trends. Cell Biol. 22, 211-219. https://doi.org/10.1016/j.tcb.2011.11.006
  80. Ewald, J. A., Desotelle, J. A., Wilding, G. and Jarrard, D. F. (2010) Therapy-induced senescence in cancer. J. Natl. Cancer Inst. 102, 1536-1546. https://doi.org/10.1093/jnci/djq364
  81. Schwarze, S. R., Fu, V. X., Desotelle, J. A., Kenowski, M. L. and Jarrard, D. F. (2005) The identification of senescence- specific genes during the induction of senescence in prostate cancer cells. Neoplasia 7, 816-823. https://doi.org/10.1593/neo.05250
  82. Asai, A., Oshima, Y., Yamamoto, Y., Uochi, T. A., Kusaka, H., Akinaga, S., Yamashita, Y., Pongracz, K., Pruzan, R., Wunder, E., Piatyszek, M., Li, S., Chin, A. C., Harley, C. B. and Gryaznov, S. (2003) A novel telomerase template antagonist (GRN163) as a potential anticancer agent. Cancer Res. 63, 3931-3939.
  83. Rebbaa, A., Zheng, X., Chu, F. and Mirkin, B. L. (2006) The role of histone acetylation versus DNA damage in drug-induced senescence and apoptosis. Cell. Death. Differ. 13, 1960-1967. https://doi.org/10.1038/sj.cdd.4401895
  84. Nardella, C., Clohessy, J. G., Alimonti, A. and Pandolfi, P. P. (2011) Pro-senescence therapy for cancer treatment. Nature. Rev. Cancer 11, 503-511. https://doi.org/10.1038/nrc3057
  85. Lee, J. J., Kim, B. C., Park, M. J., Lee, Y. S., Kim, Y. N., Lee, B. L. and Lee, J. S. (2011) PTEN status switches cell fate between premature senescence and apoptosis in glioma exposed to ionizing radiation. Cell Death. Differ. 18, 666-677. https://doi.org/10.1038/cdd.2010.139
  86. Ventura, A., Kirsch, D. G., McLaughlin, M. E., Tuveson, D. A., Grimm, J., Lintault, L., Newman, J., Reczek, E. E., Weissleder, R. and Jacks, T. (2007) Restoration of p53 function leads to tumour regression in vivo. Nature 445, 661-665. https://doi.org/10.1038/nature05541
  87. Martinkova, E., Maglott, A., Leger, D. Y., Bonnet, D., Stiborova, M., Takeda, K., Martin, S. and Dontenwill, M. (2010) alpha5beta1 integrin antagonists reduce chemotherapy- induced premature senescence and facilitate apoptosis in human glioblastoma cells. Int. J. Cancer 127, 1240-1248. https://doi.org/10.1002/ijc.25187
  88. Bykov, V. J., Issaeva, N., Shilov, A., Hultcrantz, M., Pugacheva, E., Chumakov, P., Bergman, J., Wiman, K. G. and Selivanova, G. (2002) Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat. Med. 8, 282-288. https://doi.org/10.1038/nm0302-282
  89. Michaloglou, C., Vredeveld, L. C., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M., Majoor, D. M., Shay, J. W., Mooi, W. J. and Peeper, D. S. (2005) BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720-724. https://doi.org/10.1038/nature03890
  90. Efeyan, A., Ortega-Molina, A., Velasco-Miguel, S., Herranz, D., Vassilev, L. T. and Serrano, M. (2007) Induction of p53-dependent senescence by the MDM2 antagonist nutlin-3a in mouse cells of fibroblast origin. Cancer Res. 67, 7350-7357. https://doi.org/10.1158/0008-5472.CAN-07-0200
  91. Alimonti, A., Nardella, C., Chen, Z., Clohessy, J. G., Carracedo, A., Trotman, L. C., Cheng, K., Varmeh, S., Kozma, S. C., Thomas, G., Rosivatz, E., Woscholski, R., Cognetti, F., Scher, H. I. and Pandolfi, P. P. (2010) A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J. Clin. Invest. 120, 681-693. https://doi.org/10.1172/JCI40535
  92. Benanti, J. A. and Galloway, D. A. (2004) The normal response to RAS: senescence or transformation? Cell Cycle. 3, 715-717.
  93. Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., Kastritis, E., Gilpatrick, T., Paranal, R. M., Qi, J., Chesi, M., Schinzel, A. C., McKeown, M. R., Heffernan, T. P., Vakoc, C. R., Bergsagel, P. L., Ghobrial, I. M., Richardson, P. G., Young, R. A., Hahn, W. C., Anderson, K. C., Kung, A. L., Bradner, J. E. and Mitsiades, C. S. (2011) BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146, 904-917. https://doi.org/10.1016/j.cell.2011.08.017
  94. Lee, J. J., Lee, J. H., Ko, Y. G., Hong, S. I. and Lee, J. S. (2010) Prevention of premature senescence requires JNK regulation of Bcl-2 and reactive oxygen species. Oncogene 29, 561-575. https://doi.org/10.1038/onc.2009.355
  95. Kim, B. C., Lee, H. C., Lee, J. J., Choi, C. M., Kim, D. K., Lee, J. C., Ko, Y. G. and Lee, J. S. (2012) Wig1 prevents cellular senescence by regulating p21 mRNA decay through control of RISC recruitment. EMBO J. 31, 4289-4303. https://doi.org/10.1038/emboj.2012.286

Cited by

  1. Long Term Exposure to Polyphenols of Artichoke (Cynara scolymusL.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line vol.2015, 2015, https://doi.org/10.1155/2015/363827
  2. Oroxin A inhibits breast cancer cell growth by inducing robust endoplasmic reticulum stress and senescence vol.27, pp.3, 2016, https://doi.org/10.1097/CAD.0000000000000318
  3. LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential vol.16, pp.6, 2015, https://doi.org/10.1080/15384047.2015.1040961
  4. Actin-binding doliculide causes premature senescence in p53 wild type cells vol.24, pp.2, 2016, https://doi.org/10.1016/j.bmc.2015.11.042
  5. A ‘synthetic-sickness’ screen for senescence re-engagement targets in mutant cancer backgrounds vol.13, pp.8, 2017, https://doi.org/10.1371/journal.pgen.1006942
  6. Programmed cell death in aging vol.23, 2015, https://doi.org/10.1016/j.arr.2015.04.002
  7. The influence of photodynamic therapy with 5-aminolevulinic acid on senescent skin cancer cells vol.17, 2017, https://doi.org/10.1016/j.pdpdt.2016.10.008
  8. Caveolin-1 deficiency induces premature senescence with mitochondrial dysfunction vol.16, pp.4, 2017, https://doi.org/10.1111/acel.12606
  9. The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status vol.778, 2015, https://doi.org/10.1016/j.mrfmmm.2015.06.003
  10. CBX8 antagonizes the effect of Sirtinol on premature senescence through the AKT-RB-E2F1 pathway in K562 leukemia cells vol.469, pp.4, 2016, https://doi.org/10.1016/j.bbrc.2015.12.070
  11. Polyphenols as Modulator of Oxidative Stress in Cancer Disease: New Therapeutic Strategies vol.2016, 2016, https://doi.org/10.1155/2016/6475624
  12. Heparan sulfation is essential for the prevention of cellular senescence vol.23, pp.3, 2016, https://doi.org/10.1038/cdd.2015.107
  13. P53-dependent downregulation of hTERT protein expression and telomerase activity induces senescence in lung cancer cells as a result of pterostilbene treatment vol.8, pp.8, 2017, https://doi.org/10.1038/cddis.2017.333
  14. Diindolylmethane and its halogenated derivatives induce protective autophagy in human prostate cancer cells via induction of the oncogenic protein AEG-1 and activation of AMP-activated protein kinase (AMPK) vol.40, 2017, https://doi.org/10.1016/j.cellsig.2017.09.006
  15. Trehalose inhibits cell proliferation and amplifies long-term temozolomide- and radiation-induced cytotoxicity in melanoma cells: A role for autophagy and premature senescence pp.00219541, 2018, https://doi.org/10.1002/jcp.27838
  16. 3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs pp.00063592, 2018, https://doi.org/10.1002/bit.26845
  17. Radiation-promoted CDC6 protein stability contributes to radioresistance by regulating senescence and epithelial to mesenchymal transition pp.1476-5594, 2018, https://doi.org/10.1038/s41388-018-0460-4
  18. Integrin α6β4-Src-AKT signaling induces cellular senescence by counteracting apoptosis in irradiated tumor cells and tissues pp.1476-5403, 2018, https://doi.org/10.1038/s41418-018-0114-7