The Power Behind the Throne: Senescence and the Hallmarks of Cancer

被引：23

作者：

Hoare, Matthew ^{[1
,2
]}

Narita, Masashi ^{[1
]}

机构：

[1] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England

[2] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 0QQ, England

来源：

ANNUAL REVIEW OF CANCER BIOLOGY, VOL 2 | 2018年 / 2卷

关键词：

hallmarks; cancer; senescence; microenvironment; tumor suppressor; nonautonomous; ONCOGENE-INDUCED SENESCENCE; PERSISTENT DNA-DAMAGE; CELL-CYCLE ARREST; IN-VIVO; SECRETORY PHENOTYPE; FIBROBLAST SENESCENCE; TRIGGERS SENESCENCE; TUMOR-SUPPRESSOR; LIVER-CANCER; P53;

D O I：

10.1146/annurev-cancerbio-030617-050352

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cellular senescence is a state of stable proliferative arrest triggered by various stimuli, including oncogenic and other cellular stress. Senescent cells are highly metabolically active and have diverse and profound nonautonomous effects through the senescence-associated secretory phenotype (SASP). It has become increasingly evident that senescent cells can have tumour suppressive or pro-oncogenic effects on adjacent cancer cells and other players in the tumor microenvironment such as the stroma, vasculature, and immune system. Thus, the last decade or so has witnessed a huge leap forward in our understanding of the biology of senescence, promoting it from an autonomous tumor suppressor to a complex, dynamic, and interactive phenotype. It is perhaps not a coincidence that the concept of the "hallmarks of cancer" has also evolved during this period, with the latest iteration (Hanahan & Weinberg 2011) focusing more on the microenvironment. Here, we suggest that cellular senescence could underpin the biology of many of the hallmarks of cancer, making it the true power behind the throne.

引用

页码：175 / 194

页数：20

共 135 条

[1] Chemokine signaling via the CXCR2 receptor reinforces senescence [J].

Acosta, Juan C. ;

O'Loghlen, Ana ;

Banito, Ana ;

Guijarro, Maria V. ;

Augert, Arnaud ;

Raguz, Selina ;

Fumagalli, Marzia ;

Da Costa, Marco ;

Brown, Celia ;

Popov, Nikolay ;

Takatsu, Yoshihiro ;

Melamed, Jonathan ;

di Fagagna, Fabrizio d'Adda ;

Bernard, David ;

Hernando, Eva ;

Gil, Jesus .

CELL, 2008, 133 (06) :1006-1018

[2] A complex secretory program orchestrated by the inflammasome controls paracrine senescence [J].

Acosta, Juan Carlos ;

Banito, Ana ;

Wuestefeld, Torsten ;

Georgilis, Athena ;

Janich, Peggy ;

Morton, Jennifer P. ;

Athineos, Dimitris ;

Kang, Tae-Won ;

Lasitschka, Felix ;

Andrulis, Mindaugas ;

Pascual, Gloria ;

Morris, Kelly J. ;

Khan, Sadaf ;

Jin, Hong ;

Dharmalingam, Gopuraja ;

Snijders, Ambrosius P. ;

Carroll, Thomas ;

Capper, David ;

Pritchard, Catrin ;

Inman, Gareth J. ;

Longerich, Thomas ;

Sansom, Owen J. ;

Aznar Benitah, Salvador ;

Zender, Lars ;

Gil, Jesus .

NATURE CELL BIOLOGY, 2013, 15 (08) :978-U221

[3] HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci [J].

Aird, Katherine M. ;

Iwasaki, Osamu ;

Kossenkov, Andrew V. ;

Tanizawa, Hideki ;

Fatkhutdinov, Nail ;

Bitler, Benjamin G. ;

Le, Linh ;

Alicea, Gretchen ;

Yang, Ting-Lin ;

Johnson, Brad ;

Noma, Ken-ichi ;

Zhang, Rugang .

JOURNAL OF CELL BIOLOGY, 2016, 215 (03) :325-334

[4] Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts [J].

Alcorta, DA ;

Xiong, Y ;

Phelps, D ;

Hannon, G ;

Beach, D ;

Barrett, JC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) :13742-13747

[5] The Varied Roles of Notch in Cancer [J].

Aster, Jon C. ;

Pear, Warren S. ;

Blacklow, Stephen C. .

ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 12, 2017, 12 :245-275

[6] Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging [J].

Baar, Marjolein P. ;

Brandt, Renata M. C. ;

Putavet, Diana A. ;

Klein, Julian D. D. ;

Derks, Kasper W. J. ;

Bourgeois, Benjamin R. M. ;

Stryeck, Sarah ;

Rijksen, Yvonne ;

van Willigenburg, Hester ;

Feijtel, Danny A. ;

van der Pluijm, Ingrid ;

Essers, Jeroen ;

van Cappellen, Wiggert A. ;

van IJcken, Wilfred F. ;

Houtsmuller, Adriaan B. ;

Pothof, Joris ;

de Bruin, Ron W. F. ;

Madl, Tobias ;

Hoeijmakers, Jan H. J. ;

Campisi, Judith ;

de Keizer, Peter L. J. .

CELL, 2017, 169 (01) :132-+

[7] A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends [J].

Bae, Nancy S. ;

Baumann, Peter .

MOLECULAR CELL, 2007, 26 (03) :323-334

[8] Naturally occurring p16Ink4a-positive cells shorten healthy lifespan [J].

Baker, Darren J. ;

Childs, Bennett G. ;

Durik, Matej ;

Wijers, Melinde E. ;

Sieben, Cynthia J. ;

Zhong, Jian ;

Saltness, Rachel A. ;

Jeganathan, Karthik B. ;

Verzosa, Grace Casaclang ;

Pezeshki, Abdulmohammad ;

Khazaie, Khashayarsha ;

Miller, Jordan D. ;

van Deursen, Jan M. .

NATURE, 2016, 530 (7589) :184-+

[9] Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders [J].

Baker, Darren J. ;

Wijshake, Tobias ;

Tchkonia, Tamar ;

LeBrasseur, Nathan K. ;

Childs, Bennett G. ;

van de Sluis, Bart ;

Kirkland, James L. ;

van Deursen, Jan M. .

NATURE, 2011, 479 (7372) :232-U112

[10] Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints [J].

Bartkova, Jirina ;

Rezaei, Nousin ;

Liontos, Michalis ;

Karakaidos, Panagiotis ;

Kletsas, Dimitris ;

Issaeva, Natalia ;

Vassiliou, Leandros-Vassilios F. ;

Kolettas, Evangelos ;

Niforou, Katerina ;

Zoumpourlis, Vassilis C. ;

Takaoka, Munenori ;

Nakagawa, Hiroshi ;

Tort, Frederic ;

Fugger, Kasper ;

Johansson, Fredrik ;

Sehested, Maxwell ;

Andersen, Claus L. ;

Dyrskjot, Lars ;

Orntoft, Torben ;

Lukas, Jiri ;

Kittas, Christos ;

Helleday, Thomas ;

Halazonetis, Thanos D. ;

Bartek, Jiri ;

Gorgoulis, Vassilis G. .

NATURE, 2006, 444 (7119) :633-637

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