scispace - formally typeset
Open AccessJournal ArticleDOI

A complex secretory program orchestrated by the inflammasome controls paracrine senescence

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TLDR
It is demonstrated that the SASP can cause paracrine senescence and impact on tumour suppression andSenescence in vivo and TGF-β ligands play a major role by regulating p15INK4b and p21CIP1.
Abstract
Oncogene-induced senescence (OIS) is crucial for tumour suppression. Senescent cells implement a complex pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence, activates immune surveillance and paradoxically also has pro-tumorigenic properties. Here, we present evidence that the SASP can also induce paracrine senescence in normal cells both in culture and in human and mouse models of OIS in vivo. Coupling quantitative proteomics with small-molecule screens, we identified multiple SASP components mediating paracrine senescence, including TGF-β family ligands, VEGF, CCL2 and CCL20. Amongst them, TGF-β ligands play a major role by regulating p15(INK4b) and p21(CIP1). Expression of the SASP is controlled by inflammasome-mediated IL-1 signalling. The inflammasome and IL-1 signalling are activated in senescent cells and IL-1α expression can reproduce SASP activation, resulting in senescence. Our results demonstrate that the SASP can cause paracrine senescence and impact on tumour suppression and senescence in vivo.

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Citations
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Journal ArticleDOI

Insect Navigation: How Do Wasps Get Home?

TL;DR: A new study provides precise, three-dimensional details of a wasp's head and body movements during such flights and reconstructs what the wasp sees.
Journal ArticleDOI

Senescence of Tumor Cells in Anticancer Therapy—Beneficial and Detrimental Effects

TL;DR: There is a possibility that a combination of prosenescence therapy— which targets tumor cells and causes their senescence—with senotherapy—which targets senescent cells, can be promising in cancer treatment.
Journal ArticleDOI

Potential regulators of the senescence-associated secretory phenotype during senescence and ageing.

TL;DR: This review summary summarizes in detail the potential signalling pathways that trigger and regulate SASP production during ageing and senescence.
Book ChapterDOI

The Immortal Senescence.

TL;DR: Major advances in methodologies that are being utilized for induction, identification, and characterization of molecular processes in cells undergoing oncogene-induced senescence are outlined.
Journal ArticleDOI

Tumor Secretome to Adoptive Cellular Immunotherapy: Reduce Me Before I Make You My Partner.

TL;DR: In this article, the authors review how molecules secreted in the tumor microenvironment by either tumor cells or even by immune cells impact the anti-tumor activity of surrounding immune cells.
References
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Journal ArticleDOI

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TL;DR: A consideration of the cause of the eventual degeneration of these strains leads to the hypothesis that non-cumulative external factors are excluded and that the phenomenon is attributable to intrinsic factors which are expressed as senescence at the cellular level.
Journal ArticleDOI

The limited in vitro lifetime of human diploid cell strains

TL;DR: The survival curves obtained with human diploid cell strains are comparable to “multiple-hit” or “ multiple-target” curves obtain with other biological systems where an initial threshold dose is required before an exponential form of the curve is established.
Journal ArticleDOI

Cellular senescence: when bad things happen to good cells

TL;DR: Understanding the causes and consequences of cellular senescence has provided novel insights into how cells react to stress, especially genotoxic stress, and how this cellular response can affect complex organismal processes such as the development of cancer and ageing.
Journal ArticleDOI

TGFβ in Cancer

TL;DR: The mechanistic basis and clinical relevance of TGFbeta's role in cancer is becoming increasingly clear, paving the way for a better understanding of the complexity and therapeutic potential of this pathway.
Related Papers (5)
Trending Questions (1)
Is VEGF a part of the SASP (senescence associated secretory phenotype) ?

Yes, VEGF is identified as one of the components of the SASP (senescence-associated secretory phenotype).