IFN-γ and TNF Induce Senescence and a Distinct Senescence-Associated Secretory Phenotype in Melanoma

Homann, Lorenzo; Rentschler, Maximilian; Brenner, Ellen; Böhm, Katharina; Röcken, Martin; Wieder, Thomas

doi:10.3390/cells11091514

Cited by 29 publications

(23 citation statements)

References 84 publications

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“…Cytokine dysregulation may play a key role in remodeling the immune system at older ages [ 57 ]. Proinflammatory cytokines, such as TNF-α, amplifies senescence-associated inflammation and induce senescence [ 58 ]. Additionally, metabolism plays an essential role in cell senescence, and alternative metabolism is an important part of cell senescence [ 55 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Sirt6 by CD38 promotes cell senescence and aging

Zhou

Liu

Zhang

et al. 2022

Aging

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Decreased nicotinamide adenine dinucleotide (NAD+) levels accompany aging. CD38 is the main cellular NADase. Cyanidin-3-O-glucoside (C3G), a natural inhibitor of CD38, is a well-known drug that extends the human lifespan. We investigated mechanisms of CD38 in cell senescence and C3G in antiaging. Myocardial H9c2 cells were induced to senescence with D-gal. CD38 siRNA, C3G and UBCS039 (a chemical activator of Sirt6) inhibited D-gal-induced senescence by reducing reactive oxygen species, hexokinase 2 and SA--galactosidase levels. These activators also stimulated cell proliferation and telomerase reverse transcriptase levels, while OSS-128167 (a chemical inhibitor of Sirt6) and Sirt6 siRNA exacerbated the senescent process. H9c2 cells that underwent D-gal-induced cell senescence increased CD38 expression and decreased Sirt6 expression; CD38 siRNA and C3G decreased CD38 expression and increased Sirt6 expression, respectively; and Sirt6 siRNA stimulated cell senescence in the presence of C3G and CD38 siRNA. In D-gal-induced acute aging mice, CD38 and Sirt6 exhibited increased and decreased expression, respectively, in myocardial tissues, and C3G treatment decreased CD38 expression and increased Sirt6 expression in the tissues. C3G also reduced IL-1, IL-6, IL-17A, TNF-α levels and restored NAD+ and NK cell levels in the animals. We suggest that CD38 downregulates Sirt6 expression to promote cell senescence and C3G exerts an antiaging effect through CD38-Sirt6 signaling.

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Section: Discussionmentioning

confidence: 99%

Downregulation of Sirt6 by CD38 promotes cell senescence and aging

Zhou

Liu

Zhang

et al. 2022

Aging

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“…An intriguing feature that has been noted across various cancer dormancy models is the emergence of senescent traits, encompassing the senescence-associated secretory phenotype (SASP) and expression of the β-galactosidase marker [6 ▪ ,22,34,41 ▪ ]. Within the context of cancer dormancy, senescence can restrain both proliferation and drug-induced apoptosis [42 ▪ ].…”

Section: Molecular Mechanisms Sustaining Dormancy: From Transcription...mentioning

confidence: 99%

Unveiling the role of cellular dormancy in cancer progression and recurrence

Collignon

2024

Current Opinion in Oncology

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Purpose of review Cellular dormancy is a major contributor to cancer progression and recurrence. This review explores recent findings on the molecular mechanisms implicated in cancer dormancy and investigates potential strategies to improve therapeutic interventions. Recent findings Research on cancer dormancy reveals a complex and multifaceted phenomenon. Providing a latent reservoir of tumor cells with reduced proliferation and enhanced drug-tolerance, dormant cancer cells emerge from a clonally diverse population after therapy or at metastatic sites. These cells exhibit distinct transcriptional and epigenetic profiles, involving the downregulation of Myc and mechanistic target of rapamycin (mTOR) pathways, and the induction of autophagy. Senescence traits, under the control of factors such as p53, also contribute significantly. The tumor microenvironment can either promote or prevent dormancy establishment, notably through the involvement of T and NK cells within the dormant tumor niche. Strategies to combat dormancy-related relapse include direct elimination of dormant tumor cells, sustaining dormancy to prolong survival, or awakening dormant cells to re-sensitize them to antiproliferative drugs. Summary Improving our understanding of cancer dormancy at primary and secondary sites provides valuable insights into patient care and relapse prevention.

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“…TNF-α, a multi-functional pro-inflammatory cytokine, is known to regulate apoptosis, senescence, proliferation, differentiation, and inflammation physically and pathologically [45][46][47][48]. Senescent VECs are closely associated with the development of AS.…”

Section: Tnf-αmentioning

confidence: 99%

Pro‐inflammatory cytokines mediating senescence of vascular endothelial cells in atherosclerosis

Shang

Liu

2023

Fundamemntal Clinical Pharma

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Atherosclerosis (AS) is a chronic inflammatory vascular disease, and aging is a major risk factor. The accumulation of senescent vascular endothelial cells (VECs) often leads to chronic inflammation and oxidative stress and induces endothelial dysfunction, contributing to the occurrence and development of AS. Senescent cells can secrete a variety of pro‐inflammatory cytokines to induce the senescence of adjacent cells in a paracrine manner, leading to the transmission of signaling of cellular senescence to neighboring cells and the accumulation of senescent cells. Recent studies have demonstrated that several pro‐inflammatory cytokines, including IL‐17, TNF‐α, and IFN‐γ, can induce the senescence of VECs. This review summarizes and focuses on the pro‐inflammatory cytokines that often induce the senescence of VECs and the molecular mechanisms of these pro‐inflammatory cytokines inducing senescence of VECs. Targeting the senescence of VECs induced by pro‐inflammatory cytokines may provide a potential and novel strategy for the prevention and treatment of AS.

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IFN-γ and TNF Induce Senescence and a Distinct Senescence-Associated Secretory Phenotype in Melanoma

Cited by 29 publications

References 84 publications

Downregulation of Sirt6 by CD38 promotes cell senescence and aging

Downregulation of Sirt6 by CD38 promotes cell senescence and aging

Unveiling the role of cellular dormancy in cancer progression and recurrence

Pro‐inflammatory cytokines mediating senescence of vascular endothelial cells in atherosclerosis

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