Abstract
Cellular senescence is defined as a state of stable cell-cycle arrest that is distinct from quiescence and terminal differentiation. Many stimuli can induce senescence, including telomere shortening and oncogene activation. The phenotypes elicited by pro-senescent signals can be heterogeneous depending on the stimulus and the cell type affected. To date, there is not a definitive marker that can ubiquitously and specifically mark all senescent cells. Therefore, several independent markers must be utilized to ascertain the senescent state of a cell or group of cells. Here, we describe common assays used to assess oncogenic Ras-induced senescence.
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References
Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88(5):593–602
Michaloglou C, Vredeveld LC, Soengas MS, Denoyelle C, Kuilman T, van der Horst CM et al (2005) BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436(7051):720–724
Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, Barradas M et al (2005) Tumour biology: senescence in premalignant tumours. Nature 436(7051):642
Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C et al (2006) Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444(7119):638–642
Young AR, Narita M, Ferreira M, Kirschner K, Sadaie M, Darot JF et al (2009) Autophagy mediates the mitotic senescence transition. Genes Dev 23(7):798–803
Chen H, Ruiz PD, McKimpson WM, Novikov L, Kitsis RN, Gamble MJ (2015) MacroH2A1 and ATM play opposing roles in paracrine senescence and the senescence-associated secretory phenotype. Mol Cell 59(5):719–731
Lee BY, Han JA, Im JS, Morrone A, Johung K, Goodwin EC et al (2006) Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell 5(2):187–195
Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C 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(20):9363–9367
Narita M, Nunez S, Heard E, Narita M, Lin AW, Hearn SA et al (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113(6):703–716
Di Micco R, Sulli G, Dobreva M, Liontos M, Botrugno OA, Gargiulo G et al (2011) Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer. Nat Cell Biol 13(3):292–302
Kuilman T, Michaloglou C, Vredeveld LC, Douma S, van Doorn R, Desmet CJ et al (2008) Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133(6):1019–1031
Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP et al (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15(8):978–990
Krizhanovsky V, Yon M, Dickins RA, Hearn S, Simon J, Miething C et al (2008) Senescence of activated stellate cells limits liver fibrosis. Cell 134(4):657–667
Lujambio A, Akkari L, Simon J, Grace D, Tschaharganeh DF, Bolden JE et al (2013) Non-cell-autonomous tumor suppression by p53. Cell 153(2):449–460
Freund A, Laberge RM, Demaria M, Campisi J (2012) Lamin B1 loss is a senescence-associated biomarker. Mol Biol Cell 23(11):2066–2075
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Lau, L., David, G. (2017). Senescence Phenotypes Induced by Ras in Primary Cells. In: Nikiforov, M. (eds) Oncogene-Induced Senescence. Methods in Molecular Biology, vol 1534. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6670-7_2
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DOI: https://doi.org/10.1007/978-1-4939-6670-7_2
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