The role of senescence-associated secretory phenotype (SASP) in cellular senescene

Keywords: Cellular senescence, Senescence - Associated Secretory Phenotype (SASP), tumor suppression, tumorigenesis, pro-inflammation

Abstract

Cellular senescence is one of the defense mechanisms of cells against oncogenic signals by permanently stopping the proliferation of the cell. Senescence cells show a similar characteristic, one of them is senescence-associated secretory phenotype (SASP). SASPs secrete various components, divided according to the type of molecule secreted and based on their mechanism of action against target cells. The main components of SASP are pro-inflammatory mediators. SASP performs dual and contradictory roles, which concurrently provides beneficial effects such as tumor suppression due to the termination of proliferation, recruitment of immune cells, and tissue repair. On the other hand, SASP produces detrimental effects on cells undergoing the senescence process as well as cells in the surrounding environment by increasing tumorigenesis. This review article explains the various components of the SASP, the role of SASP in the inflammatory process, tumor suppression, and tumorigenesis.

References

Salminen A, Kauppinen A, Kaarniranta K. Emerging role of NF-κB signaling in the induction of senescence-associated secretory phenotype (SASP). Cell Signal. 2012;24: 835-845. https://doi.org/10.1016/j.cellsig.2011.12.006

Byun H-O, Lee Y-K, Kim J-M, Yoon G. From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes. BMB Rep. 2015;48: 549-558. https://doi.org/10.5483/BMBRep.2015.48.10.122

Walters HE, Cox LS. Generation of a novel model of primary human cell senescence through Tenovin-6 mediated inhibition of sirtuins. Biogerontology. 2019;20: 303-319. https://doi.org/10.1007/s10522-018-09792-0

Bernadotte A, Mikhelson VM, Spivak IM. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence. Aging (Albany, NY). 2016;8: 3-11. https://doi.org/10.18632/aging.100871

Srinivas N, Rachakonda S, Kumar R. Telomeres and telomere length: A general overview. Cancers (Basel). 2020;12. https://doi.org/10.3390/cancers12030558

Wang B, Kohli J, Demaria M. Senescent cells in cancer therapy: friends or foes? Trends Cancer. 2020;6: 838-857. https://doi.org/10.1016/j.trecan.2020.05.004

Herranz N, Gil J. Mechanisms and functions of cellular senescence. J Clin Invest. 2018;128: 1238-1246. https://doi.org/10.1172/JCI95148

Amaya-Montoya M, Pérez-Londoño A, Guatibonza-García V, Vargas-Villanueva A, Mendivil CO. Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review. Adv Ther. 2020;37: 1407-1424. https://doi.org/10.1007/s12325-020-01287-0

Kumari R, Jat P. Mechanisms of cellular senescence: cell cycle arrest and senescence associated secretory phenotype. Front Cell Dev Biol. 2021;9: 645593. https://doi.org/10.3389/fcell.2021.645593

Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell. 2007;130: 223-233. https://doi.org/10.1016/j.cell.2007.07.003

Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005;120: 513-522. https://doi.org/10.1016/j.cell.2005.02.003

Takahashi A, Ohtani N, Yamakoshi K, Iida S, Tahara H, Nakayama K, et al. Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce irreversible cellular senescence. Nat Cell Biol. 2006;8: 1291-1297. https://doi.org/10.1038/ncb1491

Yang J, Xu Z-P, Huang Y, Hamrick HE, Duerksen-Hughes PJ, Yu Y-N. ATM and ATR: sensing DNA damage. World J Gastroenterol. 2004;10: 155-160. https://doi.org/10.3748/wjg.v10.i2.155

Lopes-Paciencia S, Saint-Germain E, Rowell M-C, Ruiz AF, Kalegari P, Ferbeyre G. The senescence-associated secretory phenotype and its regulation. Cytokine. 2019;117: 15-22. https://doi.org/10.1016/j.cyto.2019.01.013

van Deursen JM. The role of senescent cells in ageing. Nature. 2014;509: 439-446. https://doi.org/10.1038/nature13193

Schafer MJ, Zhang X, Kumar A, Atkinson EJ, Zhu Y, Jachim S, et al. The senescence-associated secretome as an indicator of age and medical risk. JCI Insight. 2020; https://doi.org/10.1172/jci.insight.133668

Chambers CR, Ritchie S, Pereira BA, Timpson P. Overcoming the senescence-associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer. Mol Oncol. 2021;15: 3242-3255. https://doi.org/10.1002/1878-0261.13042

Liu M, Yuan T, Liu H, Chen P. CCAAT/enhancer-binding protein β regulates interleukin-6-induced transmembrane and ubiquitin-like domain containing 1 gene expression in hepatocytes. Mol Med Rep. 2014;10: 2177-2183. https://doi.org/10.3892/mmr.2014.2457

Cuollo L, Antonangeli F, Santoni A, Soriani A. The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases. Biology (Basel). 2020;9. https://doi.org/10.3390/biology9120485

Sebban H, Yamaoka S, Courtois G. Posttranslational modifications of NEMO and its partners in NF-kappaB signaling. Trends Cell Biol. 2006;16: 569-577. https://doi.org/10.1016/j.tcb.2006.09.004

Wu Z-H, Wong ET, Shi Y, Niu J, Chen Z, Miyamoto S, et al. ATM- and NEMO-dependent ELKS ubiquitination coordinates TAK1-mediated IKK activation in response to genotoxic stress. Mol Cell. 2010;40: 75-86. https://doi.org/10.1016/j.molcel.2010.09.010

Coulthard LR, White DE, Jones DL, McDermott MF, Burchill SA. p38(MAPK): stress responses from molecular mechanisms to therapeutics. Trends Mol Med. 2009;15: 369-379. https://doi.org/10.1016/j.molmed.2009.06.005

Dodeller F, Gottar M, Huesken D, Iourgenko V, Cenni B. The lysosomal transmembrane protein 9B regulates the activity of inflammatory signaling pathways. J Biol Chem. 2008;283: 21487-21494. https://doi.org/10.1074/jbc.M801908200

Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP, et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013;15: 978-990. https://doi.org/10.1038/ncb2784

Liu G, Zhang F, Lee J, Dong Z. Selective induction of interleukin-8 expression in metastatic melanoma cells by transforming growth factor-beta 1. Cytokine. 2005;31: 241-249. https://doi.org/10.1016/j.cyto.2005.03.008

Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, et al. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science. 2015;349: aaa5612. https://doi.org/10.1126/science.aaa5612

Borodkina AV, Deryabin PI, Giukova AA, Nikolsky NN. "social life" of senescent cells: what is SASP and why study it? Acta Naturae. 2018;10: 4-14. https://doi.org/10.32607/20758251-2018-10-1-4-14

Salminen A, Kaarniranta K. Control of p53 and NF-κB signaling by WIP1 and MIF: role in cellular senescence and organismal aging. Cell Signal. 2011;23: 747-752. https://doi.org/10.1016/j.cellsig.2010.10.012

Liu F, Wu S, Ren H, Gu J. Klotho suppresses RIG-I-mediated senescence-associated inflammation. Nat Cell Biol. 2011;13: 254-262. https://doi.org/10.1038/ncb2167

Cánepa ET, Scassa ME, Ceruti JM, Marazita MC, Carcagno AL, Sirkin PF, et al. INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions. IUBMB Life. 2007;59: 419-426. https://doi.org/10.1080/15216540701488358

Cheung CT, Kaul SC, Wadhwa R. Molecular bridging of aging and cancer: A CARF link. Ann N Y Acad Sci. 2010;1197: 129-133. https://doi.org/10.1111/j.1749-6632.2009.05392.x

Davalos AR, Coppe J-P, Campisi J, Desprez P-Y. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev. 2010;29: 273-283. https://doi.org/10.1007/s10555-010-9220-9

Coppé J-P, Desprez P-Y, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010;5: 99-118. https://doi.org/10.1146/annurev-pathol-121808-102144

Dasgupta J, Kar S, Liu R, Joseph J, Kalyanaraman B, Remington SJ, et al. Reactive oxygen species control senescence-associated matrix metalloproteinase-1 through c-Jun-N-terminal kinase. J Cell Physiol. 2010;225: 52-62. https://doi.org/10.1002/jcp.22193

Kuilman T, Michaloglou C, Vredeveld LCW, Douma S, van Doorn R, Desmet CJ, et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell. 2008;133: 1019-1031. https://doi.org/10.1016/j.cell.2008.03.039

Reichenstein M, Reich R, LeHoux J-G, Hanukoglu I. ACTH induces TIMP-1 expression and inhibits collagenase in adrenal cortex cells. Mol Cell Endocrinol. 2004;215: 109-114. https://doi.org/10.1016/j.mce.2003.11.011

Cesari M, Pahor M, Incalzi RA. Plasminogen activator inhibitor-1 (PAI-1): a key factor linking fibrinolysis and age-related subclinical and clinical conditions. Cardiovasc Ther. 2010;28: e72-91. https://doi.org/10.1111/j.1755-5922.2010.00171.x

Rajpathak SN, Gunter MJ, Wylie-Rosett J, Ho GYF, Kaplan RC, Muzumdar R, et al. The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes. Diabetes Metab Res Rev. 2009;25: 3-12. https://doi.org/10.1002/dmrr.919

Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol. 2013;75: 685-705. https://doi.org/10.1146/annurev-physiol-030212-183653

Hinds P, Pietruska J. Senescence and tumor suppression. [version 1; peer review: 2 approved]. F1000Res. 2017;6: 2121. https://doi.org/10.12688/f1000research.11671.1

Kortlever RM, Higgins PJ, Bernards R. Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nat Cell Biol. 2006;8: 877-884. https://doi.org/10.1038/ncb1448

Zhang W, Ling D, Tan J, Zhang J, Li L. Expression of urokinase plasminogen activator and plasminogen activator inhibitor type-1 in ovarian cancer and its clinical significance. Oncol Rep. 2013;29: 637-645. https://doi.org/10.3892/or.2012.2148

Pereira BI, Devine OP, Vukmanovic-Stejic M, Chambers ES, Subramanian P, Patel N, et al. Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition. Nat Commun. 2019;10: 2387. https://doi.org/10.1038/s41467-019-10335-5

Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453: 314-321. https://doi.org/10.1038/nature07039

Gieseck RL, Wilson MS, Wynn TA. Type 2 immunity in tissue repair and fibrosis. Nat Rev Immunol. 2018;18: 62-76. https://doi.org/10.1038/nri.2017.90

Lee S, Ahad A, Luu M, Moon S, Caesar J, Cardoso WV, et al. CCN1-Yes-Associated Protein Feedback Loop Regulates Physiological and Pathological Angiogenesis. Mol Cell Biol. 2019;39. https://doi.org/10.1128/MCB.00107-19

Jun J-I, Lau LF. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat Cell Biol. 2010;12: 676-685. https://doi.org/10.1038/ncb2070

Campisi J, Andersen JK, Kapahi P, Melov S. Cellular senescence: a link between cancer and age-related degenerative disease? Semin Cancer Biol. 2011;21: 354-359. https://doi.org/10.1016/j.semcancer.2011.09.001

Noureddine H, Gary-Bobo G, Alifano M, Marcos E, Saker M, Vienney N, et al. Pulmonary artery smooth muscle cell senescence is a pathogenic mechanism for pulmonary hypertension in chronic lung disease. Circ Res. 2011;109: 543-553. https://doi.org/10.1161/CIRCRESAHA.111.241299

Liu D, Hornsby PJ. Senescent human fibroblasts increase the early growth of xenograft tumors via matrix metalloproteinase secretion. Cancer Res. 2007;67: 3117-3126. https://doi.org/10.1158/0008-5472.CAN-06-3452

Kim K-H, Park G-T, Lim Y-B, Rue S-W, Jung J-C, Sonn J-K, et al. Expression of connective tissue growth factor, a biomarker in senescence of human diploid fibroblasts, is up-regulated by a transforming growth factor-beta-mediated signaling pathway. Biochem Biophys Res Commun. 2004;318: 819-825. https://doi.org/10.1016/j.bbrc.2004.04.108

Yang F, Tuxhorn JA, Ressler SJ, McAlhany SJ, Dang TD, Rowley DR. Stromal expression of connective tissue growth factor promotes angiogenesis and prostate cancer tumorigenesis. Cancer Res. 2005;65: 8887-8895. https://doi.org/10.1158/0008-5472.CAN-05-1702

Dhawan P, Richmond A. Role of CXCL1 in tumorigenesis of melanoma. J Leukoc Biol. 2002;72: 9-18.

Coppé J-P, Kauser K, Campisi J, Beauséjour CM. Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence. J Biol Chem. 2006;281: 29568-29574. https://doi.org/10.1074/jbc.M603307200

Tonini T, Rossi F, Claudio PP. Molecular basis of angiogenesis and cancer. Oncogene. 2003;22: 6549-6556. https://doi.org/10.1038/sj.onc.1206816

Coppé J-P, Patil CK, Rodier F, Sun Y, Muñoz 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: 2853-2868. https://doi.org/10.1371/journal.pbio.0060301

Parrinello S, Coppe J-P, Krtolica A, Campisi J. Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. J Cell Sci. 2005;118: 485-496. https://doi.org/10.1242/jcs.01635

Birch J, Gil J. Senescence and the SASP: many therapeutic avenues. Genes Dev. 2020;34: 1565-1576. https://doi.org/10.1101/gad.343129.120

Nakagami H. Cellular senescence and senescence-associated T cells as a potential therapeutic target. Geriatr Gerontol Int. 2020;20: 97-100. https://doi.org/10.1111/ggi.13851

Nesbit M, Schaider H, Miller TH, Herlyn M. Low-level monocyte chemoattractant protein-1 stimulation of monocytes leads to tumor formation in nontumorigenic melanoma cells. J Immunol. 2001;166: 6483-6490. https://doi.org/10.4049/jimmunol.166.11.6483

Lecot P, Alimirah F, Desprez P-Y, Campisi J, Wiley C. Context-dependent effects of cellular senescence in cancer development. Br J Cancer. 2016;114: 1180-1184. https://doi.org/10.1038/bjc.2016.115

Published
2021-12-31
How to Cite
de Lima, F. V. I., & Hardiany, N. S. (2021). The role of senescence-associated secretory phenotype (SASP) in cellular senescene. Acta Biochimica Indonesiana, 4(2), 33. https://doi.org/10.32889/actabioina.33