Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy
Abstract
:1. Introduction
2. Cancer Stem Cells
3. Senescence and Stemness Are Relevant in Cancer Evolution
3.1. The Senescent Phenotype
3.2. Senescence Promotes Intrinsic and Paracrine Stemness
3.3. Senescence Induction on Stem Cells and Cancer Stem Cells
4. Role of Tumor Suppressor and Oncogenic Pathways in Senescence
5. Therapy-Induced Senescence
6. Senescence Implications in Metastasis
7. Tumor Cell Dormancy
Dormancy and Metastatic Recurrence
8. Molecular Mechanisms Underlying Dormancy, Quiescence, and Senescence
Primary Signaling in Dormancy and its Relevance for Cancer Stem-Like and Senescent Cells
9. Dormant and Senescent Cells: One and the Same or Another Kind?
9.1. TGF-β Family Factors in Dormancy and Senescence
9.2. CDK Inhibitors in Dormancy, Quiescence, and Senescence
9.3. Emerging Molecular Mechanisms Controlling Quiescent or Senescent Fate
10. Microenvironment Influences Dormancy and Senescence
10.1. Microenvironment and Dormancy Induction
10.2. Senescent Secretome in a Dormancy Context
10.3. Immune Recognition and Clearance of Dormant and Senescent Cells
10.4. The Awaking of Dormant Cells is Primarily Promoted by the Microenvironment
11. Two Models of Tumor Dormancy
12. Senolytic Therapy Is Beneficial in Cancer
12.1. Experimental Evidence Highlights the Efficacy of Senolytics as a Cancer Treatment
12.2. Senolytics in Clinical Development
13. Outlook
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AML | Acute myeloid leukemia |
BMP | Bone morphogenetic protein |
BMPR | Bone morphogenetic protein receptor |
CCL | chemokine (C-C motif) ligand |
CDK | Cyclin-dependent kinase |
CSC | Cancer stem cells |
CSF3 | Granulocyte colony-stimulating factor |
CTC | Circulating tumor cells |
CXCL | C-X-C motif chemokine |
DDR | DNA damage response |
DoTC | Dormant tumor cells |
DREAM | Dimerization partner, RB-like, E2F, and multi-vulval class B |
DTC | Disseminated tumor cells |
DYRK | Dual specificity tyrosine-phosphorylation-regulated kinase |
EGF | Epidermal growth factor |
EMT | Epithelial-mesenchymal transition |
ERK | Extracellular signal–regulated kinase |
FAK | Focal adhesion kinase |
Gas6 | Growth-arrest specific 6 |
GDF | Growth/differentiation factor |
HGF | Hepatocyte growth factor |
IGF | Insulin-like growth factor 1 |
IGFR | Insulin-like growth factor receptor |
iPS | Induced pluripotent stem cell |
MSC | Mesenchymal stem/stromal cells |
MuvB | Multi-vulval class B |
MYLK | Myosin light-chain kinase |
NR2F1 | Nuclear Receptor subfamily 2, group F, member 1 |
OIS | Oncogene-Induced Senescence |
RANK | Receptor activator of nuclear factor κ B |
RCCC | Rapid-cycling cancer cells |
SAHF | Senescence-associated heterochromatin foci |
SASP | Senescence associated secretory phenotype |
SCCC | Slow-cycling cancer cells |
SPARC | Secreted protein acidic and rich in cysteine |
TGF-β | Transforming growth factor beta |
TGS | Tumor necrosis factor-inducible gene |
TIS | Therapy induced senescence |
TNF-α | Tumor necrosis factor alpha |
VEGF | Vascular endothelial growth factor |
YAP | Yes-associated protein |
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Fate | Genetic Origin | Trigger Signal | Tumor Mass/Tumor Cell Outcome | Current and Prospective * Therapeutic Interventions |
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Stemness |
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Quiescence |
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Dormancy |
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Cell cycle re-entry |
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Senescence |
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Proliferation |
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Triana-Martínez, F.; Loza, M.I.; Domínguez, E. Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy. Cells 2020, 9, 346. https://doi.org/10.3390/cells9020346
Triana-Martínez F, Loza MI, Domínguez E. Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy. Cells. 2020; 9(2):346. https://doi.org/10.3390/cells9020346
Chicago/Turabian StyleTriana-Martínez, Francisco, María Isabel Loza, and Eduardo Domínguez. 2020. "Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy" Cells 9, no. 2: 346. https://doi.org/10.3390/cells9020346
APA StyleTriana-Martínez, F., Loza, M. I., & Domínguez, E. (2020). Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy. Cells, 9(2), 346. https://doi.org/10.3390/cells9020346