Senescent Cells in Cancer: Wanted or Unwanted Citizens
Abstract
:1. Introduction
2. Cellular Senescence
2.1. Inducers of Senescence
2.2. Molecular Pathways Leading to Senescence
2.3. Markers and Characteristics of Senescent Cells
3. The Senescence-Associated Secretory Phenotype
3.1. Characteristics and Functions
3.2. Pathways Involved in the Regulation of the SASP
4. Cellular Senescence and Cancer
4.1. The SASP as a Tumour-Promoting Mechanism
4.2. Therapy Induced Senescence and Its Implications
5. Targeting Senescent Cells in Cancer
5.1. Senomorphic Agents
5.2. Senolytic Agents
5.3. Future Perspectives
6. Concluding Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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SASP Factors | |
---|---|
Inflammatory cytokines | IL-6, IL-7, IL-1⍺, IL-1β, IL-11, IL-13, IL-15 |
Chemokines | CXCL8 (IL-8), CXCL-1, -2, -3, -19, MCP-1, -2, -3, -4, MIP-1a, MIP-3a, HCC-4, Eotaxin-3, I-309 |
Growth factors and regulators | VEGF, EGF, HGF, KGF, Amphiregulin, Epiregulin, Heregulin, Angiogenin, SCF, SDF-1, IGFBP-1, -2, -3, -4, -5, -6, -7, IGFBP-rP1, -2 |
Protease and regulators | MMP-1, -3, -10, -12, -13, -14, TIMP-2, PAI-1, -2, uPa, tPa, Cathepsin B |
Others | PGE2, Nitric oxide, ROS, ICAM-1, -3, OPG, sTNFRI, TRAIL-R3, Fas, uPAR, SGP130, EGF-3, Leptin, Osteoprotegerin, SCF, Extracellular vesicles, MIF, GM-CSF, G-CSF |
SENOMORPHICS | ||
Agent | Mode of Action | Refs |
Glucocorticoids | Inhibits arachinoid acid metabolism | [124] |
Aventhramice C (Avn C) | Inhibits NF-κB signalling | [125] |
Metformin | Inhibits NF-κB signalling | [126,127] |
Interleukin 1 receptor antagonist (Anakinra) | IL-1 inhibitor | [8,10,72,77] |
Rapamycin | mTOR inhibitor | [65,67] |
Roxadustat | Hypoxia-mimetic, targets mTOR | [66] |
2,3-dihydroxybenzoic acid | Hypoxia-mimetic, HIF prolyl hydroxylase inhibitor | [66] |
C75 | Fatty acid synthase (FASN) inhibitor | [128] |
RU.521 | cGAS inhibitor | [74] |
Y-27632 | Rho kinase (ROCK) inhibitor | [129,130] |
Simvastatin | Targets IL-6, IL-8 and MCP1 | [131] |
SENOLYTICS | ||
Agent | Mode of Action | Refs |
AT-406 | Regulates anti-apoptotic proteins c-IAP2 and XIAP | [122] |
ABT263 | Bcl-2 and Bcl-xl inhibitor | [132] |
Navitoclax | Bcl-2 and Bcl-xl inhibitor | [133] |
Dasatinib | Tyrosine kinase inhibitor | [86,134] |
Quercetin | Flavonoid | [86,134] |
Fisetin | Flavonoidº | [135,136] |
A1331852 | Selective Bcl-xl inhibitor | [135] |
A1155463 | Selective Bcl-xl inhibitor | [135] |
Geldanamycin | HSP90 inhibitor | [137] |
17-AAG (tanespimycin) | HSP90 inhibitor | [137] |
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Niklander, S.E.; Lambert, D.W.; Hunter, K.D. Senescent Cells in Cancer: Wanted or Unwanted Citizens. Cells 2021, 10, 3315. https://doi.org/10.3390/cells10123315
Niklander SE, Lambert DW, Hunter KD. Senescent Cells in Cancer: Wanted or Unwanted Citizens. Cells. 2021; 10(12):3315. https://doi.org/10.3390/cells10123315
Chicago/Turabian StyleNiklander, Sven E., Daniel W. Lambert, and Keith D. Hunter. 2021. "Senescent Cells in Cancer: Wanted or Unwanted Citizens" Cells 10, no. 12: 3315. https://doi.org/10.3390/cells10123315
APA StyleNiklander, S. E., Lambert, D. W., & Hunter, K. D. (2021). Senescent Cells in Cancer: Wanted or Unwanted Citizens. Cells, 10(12), 3315. https://doi.org/10.3390/cells10123315