DOI QR코드

DOI QR Code

Cellular senescence in cancer

  • Kim, Young Hwa (Department of Biochemistry and Molecular Biology, Ajou University School of Medicine) ;
  • Park, Tae Jun (Department of Biochemistry and Molecular Biology, Ajou University School of Medicine)
  • 투고 : 2018.10.24
  • 발행 : 2019.01.31

초록

Cellular senescence, a process of cell proliferation arrest in response to various stressors, has been considered to be important factor in age-related disease. Identification of senescent cells in tissues is limited and the role of senescent cells is poorly understood. Recently however, several studies showed the characterization of senescent cells in various pathologic conditions and the role of senescent cells in disease progression is becoming important. Senescent cells are growth-arrested cells, however, the senescence associated secretory phenotype (SASP) of senescent cells could modify the tissues' microenvironment. Here, we discuss the progress and understanding of the role of senescent cells in tissues of pathologic conditions and discuss the development of new therapeutic paradigms, such as senescent cells-targeted therapy.

키워드

참고문헌

  1. Hayflick L and Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25, 585-621 https://doi.org/10.1016/0014-4827(61)90192-6
  2. Herbert B, Pitts AE, Baker SI et al (1999) Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc Natl Acad Sci U S A 96, 14276-14281 https://doi.org/10.1073/pnas.96.25.14276
  3. Baird DM, Rowson J, Wynford-Thomas D and Kipling D (2003) Extensive allelic variation and ultrashort telomeres in senescent human cells. Nat Genet 33, 203-207 https://doi.org/10.1038/ng1084
  4. Baerlocher GM, Mak J, Roth A, Rice KS and Lansdorp PM (2003) Telomere shortening in leukocyte subpopulations from baboons. J Leukoc Biol 73, 289-296 https://doi.org/10.1189/jlb.0702361
  5. Lopez-Otin C, Blasco MA, 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
  6. Kuilman T, Michaloglou C, Mooi WJ and Peeper DS (2010) The essence of senescence. Genes Dev 24, 2463-2479 https://doi.org/10.1101/gad.1971610
  7. Collado M, Blasco MA and Serrano M (2007) Cellular senescence in cancer and aging. Cell 130, 223-233 https://doi.org/10.1016/j.cell.2007.07.003
  8. Campisi J and d'Adda di Fagagna F (2007) Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8, 729-740 https://doi.org/10.1038/nrm2233
  9. Storer M, Mas A, Robert-Moreno A et al (2013) Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 155, 1119-1130 https://doi.org/10.1016/j.cell.2013.10.041
  10. Munoz-Espin D, Canamero M, Maraver A et al (2013) Programmed cell senescence during mammalian embryonic development. Cell 155, 1104-1118 https://doi.org/10.1016/j.cell.2013.10.019
  11. Baker DJ, Wijshake T, Tchkonia T et al (2011) Clearance of p16Ink4a-positive senescent cells delays ageingassociated disorders. Nature 479, 232-236 https://doi.org/10.1038/nature10600
  12. Martin JA and Buckwalter JA (2002) Aging, articular cartilage chondrocyte senescence and osteoarthritis. Biogerontology 3, 257-264 https://doi.org/10.1023/A:1020185404126
  13. Minamino T and Komuro I (2007) Vascular cell senescence: contribution to atherosclerosis. Circ Res 100, 15-26 https://doi.org/10.1161/01.RES.0000256837.40544.4a
  14. Childs BG, Durik M, Baker DJ and van Deursen JM (2015) Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med 21, 1424-1435 https://doi.org/10.1038/nm.4000
  15. Bodnar AG, Ouellette M, Frolkis M et al (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349-352 https://doi.org/10.1126/science.279.5349.349
  16. Munoz-Espin D and Serrano M (2014) Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 15, 482-496 https://doi.org/10.1038/nrm3823
  17. Vicente R, Mausset-Bonnefont AL, Jorgensen C, Louis-Plence P and Brondello JM (2016) Cellular senescence impact on immune cell fate and function. Aging Cell 15, 400-406 https://doi.org/10.1111/acel.12455
  18. Tchkonia T, Zhu Y, van Deursen J, Campisi J and Kirkland JL (2013) Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 123, 966-972 https://doi.org/10.1172/JCI64098
  19. Serrano M, Lin AW, McCurrach ME, Beach D and Lowe SW (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
  20. Chen Z, Trotman LC, Shaffer D et al (2005) Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436, 725-730 https://doi.org/10.1038/nature03918
  21. Michaloglou C, Vredeveld LC, Soengas MS et al (2005) BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720-724 https://doi.org/10.1038/nature03890
  22. Althubiti M, Lezina L, Carrera S et al (2014) Characterization of novel markers of senescence and their prognostic potential in cancer. Cell Death Dis 5, e1528 https://doi.org/10.1038/cddis.2014.489
  23. Collado M, Gil J, Efeyan A et al (2005) Tumour biology: senescence in premalignant tumours. Nature 436, 642 https://doi.org/10.1038/436642a
  24. Krtolica A, Parrinello S, Lockett S, Desprez PY and Campisi J (2001) Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci U S A 98, 12072-12077 https://doi.org/10.1073/pnas.211053698
  25. Haugstetter AM, Loddenkemper C, Lenze D et al (2010) Cellular senescence predicts treatment outcome in metastasised colorectal cancer. Br J Cancer 103, 505-509 https://doi.org/10.1038/sj.bjc.6605784
  26. Reimann M, Lee S, Loddenkemper C et al (2010) Tumor stroma-derived TGF-beta limits myc-driven lymphomagenesis via Suv39h1-dependent senescence. Cancer Cell 17, 262-272 https://doi.org/10.1016/j.ccr.2009.12.043
  27. Vizioli MG, Possik PA, Tarantino E et al (2011) Evidence of oncogene-induced senescence in thyroid carcinogenesis. Endocr Relat Cancer 18, 743-757 https://doi.org/10.1530/ERC-11-0240
  28. Kim YH, Choi YW, Lee J, Soh EY, Kim JH and Park TJ (2017) Senescent tumor cells lead the collective invasion in thyroid cancer. Nat Commun 8, 15208 https://doi.org/10.1038/ncomms15208
  29. Denoyelle C, Abou-Rjaily G, Bezrookove V et al (2006) Anti-oncogenic role of the endoplasmic reticulum differentially activated by mutations in the MAPK pathway. Nat Cell Biol 8, 1053-1063 https://doi.org/10.1038/ncb1471
  30. Debacq-Chainiaux F, Erusalimsky JD, Campisi J and Toussaint O (2009) Protocols to detect senescenceassociated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nat Protoc 4, 1798-1806 https://doi.org/10.1038/nprot.2009.191
  31. Dimri GP, Lee X, Basile G et al (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
  32. Yoon JE, Kim Y, Kwon S et al (2018) Senescent fibroblasts drive ageing pigmentation: A potential therapeutic target for senile lentigo. Theranostics 8, 4620-4632 https://doi.org/10.7150/thno.26975
  33. Bennecke M, Kriegl L, Bajbouj M et al (2010) Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis. Cancer Cell 18, 135-146 https://doi.org/10.1016/j.ccr.2010.06.013
  34. Ancrile B, Lim KH and Counter CM (2007) Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev 21, 1714-1719 https://doi.org/10.1101/gad.1549407
  35. Sparmann A and Bar-Sagi D (2004) Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 6, 447-458 https://doi.org/10.1016/j.ccr.2004.09.028
  36. el-Deiry WS, Harper JW, O'Connor PM et al (1994) WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 54, 1169-1174
  37. Di Leonardo A, Linke SP, Clarkin K and Wahl GM (1994) DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts. Genes Dev 8, 2540-2551 https://doi.org/10.1101/gad.8.21.2540
  38. Liu M and Pelling JC (1995) UV-B/A irradiation of mouse keratinocytes results in p53-mediated WAF1/CIP1 expression. Oncogene 10, 1955-1960
  39. Stein GH, Drullinger LF, Soulard A and Dulic V (1999) Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. Mol Cell Biol 19, 2109-2117 https://doi.org/10.1128/MCB.19.3.2109
  40. Lee CJ, Suh EJ, Kang HT et al (2002) Induction of senescence-like state and suppression of telomerase activity through inhibition of HPV E6/E7 gene expression in cells immortalized by HPV16 DNA. Exp Cell Res 277, 173-182 https://doi.org/10.1006/excr.2002.5554
  41. Gabay C (2006) Interleukin-6 and chronic inflammation. Arthritis Res Ther 8 Suppl 2, S3 https://doi.org/10.1186/ar1917
  42. Kunkel SL, Standiford T, Kasahara K and Strieter RM (1991) Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung. Exp Lung Res 17, 17-23 https://doi.org/10.3109/01902149109063278
  43. Coppe JP, Desprez PY, 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
  44. Freund A, Orjalo AV, Desprez PY and Campisi J (2010) Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med 16, 238-246 https://doi.org/10.1016/j.molmed.2010.03.003
  45. Liu D and Hornsby PJ (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
  46. Parrinello S, Coppe JP, 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. Biran A, Zada L, Abou Karam P et al (2017) Quantitative identification of senescent cells in aging and disease. Aging Cell 16, 661-671 https://doi.org/10.1111/acel.12592
  48. Jun JI and Lau LF (2010) The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat Cell Biol 12, 676-685 https://doi.org/10.1038/ncb2070
  49. Krizhanovsky V, Yon M, Dickins RA et al (2008) Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657-667 https://doi.org/10.1016/j.cell.2008.06.049
  50. Coppe JP, Patil CK, Rodier F et al (2008) Senescenceassociated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6, 2853-2868
  51. Kim YH, Choi YW, Han JH et al (2014) TSH signaling overcomes B-RafV600E-induced senescence in papillary thyroid carcinogenesis through regulation of DUSP6. Neoplasia 16, 1107-1120 https://doi.org/10.1016/j.neo.2014.10.005
  52. Cisowski J, Sayin VI, Liu M, Karlsson C and Bergo MO (2016) Oncogene-induced senescence underlies the mutual exclusive nature of oncogenic KRAS and BRAF. Oncogene 35, 1328-1333 https://doi.org/10.1038/onc.2015.186
  53. Dankort D, Curley DP, Cartlidge RA et al (2009) Braf(V600E) cooperates with Pten loss to induce metastatic melanoma. Nat Genet 41, 544-552 https://doi.org/10.1038/ng.356
  54. Bos JL (1989) ras oncogenes in human cancer: a review. Cancer Res 49, 4682-4689
  55. Milde-Langosch K, Bamberger AM, Rieck G, Kelp B and Loning T (2001) Overexpression of the p16 cell cycle inhibitor in breast cancer is associated with a more malignant phenotype. Breast Cancer Res Treat 67, 61-70 https://doi.org/10.1023/A:1010623308275
  56. Jaszewski R, Ehrinpreis MN and Majumdar AP (1999) Aging and cancer of the stomach and colon. Front Biosci 4, D322-328 https://doi.org/10.2741/A430
  57. Bleul CC, Farzan M, Choe H et al (1996) The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382, 829-833 https://doi.org/10.1038/382829a0
  58. Ho IA, Yulyana Y, Sia KC et al (2014) Matrix metalloproteinase-1-mediated mesenchymal stem cell tumor tropism is dependent on crosstalk with stromal derived growth factor 1/C-X-C chemokine receptor 4 axis. FASEB J 28, 4359-4368 https://doi.org/10.1096/fj.14-252551
  59. Chen JH, Stoeber K, Kingsbury S, Ozanne SE, Williams GH and Hales CN (2004) Loss of proliferative capacity and induction of senescence in oxidatively stressed human fibroblasts. J Biol Chem 279, 49439-49446 https://doi.org/10.1074/jbc.M409153200