Regulation of senescence escape by TSP1 and CD47 following chemotherapy treatment

Cell Death & Disease
Jordan GuillonOlivier Coqueret

Abstract

Senescence is a tumor-suppressive mechanism induced by telomere shortening, oncogenes, or chemotherapy treatment. Although it is clear that this suppressive pathway leads to a permanent arrest in primary cells, this might not be the case in cancer cells that have inactivated their suppressive pathways. We have recently shown that subpopulations of cells can escape chemotherapy-mediated senescence and emerge as more transformed cells that induce tumor formation, resist anoikis, and are more invasive. In this study, we characterized this emergence and showed that senescent cells favor tumor growth and metastasis, in vitro and in vivo. Senescence escape was regulated by secreted proteins produced during emergence. Among these, we identified thrombospondin-1 (TSP1), a protein produced by senescent cells that prevented senescence escape. Using SWATH quantitative proteomic analysis, we found that TSP1 can be detected in the serum of patients suffering from triple-negative breast cancer and that its low expression was associated with treatment failure. The results also indicate that senescence escape is explained by the emergence of CD47low cells that express a reduced level of CD47, the TSP1 receptor. The results show that CD47 expre...Continue Reading

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Citations

Apr 11, 2019·Proteomics·Coralie PetitOlivier Coqueret
Oct 3, 2019·Development·Muriel RhinnWilliam M Keyes
May 7, 2020·American Journal of Physiology. Cell Physiology·Jeffrey S Isenberg, David D Roberts
Jul 10, 2020·Cancers·Małgorzata Milczarek
Jul 26, 2019·Oxidative Medicine and Cellular Longevity·Barbara MarengoCinzia Domenicotti
Apr 24, 2020·Frontiers in Pharmacology·Hélène GrégoireEmmanuel Garcion
Sep 28, 2020·Molecular Oncology·Hui-Ling OuDaniel Muñoz-Espín
Aug 14, 2019·Cancer Letters·Olivier PluquetOlivier Coqueret
Feb 1, 2021·Briefings in Bioinformatics·Jianjun JiangQingpeng Kong
Feb 14, 2021·Cancers·Valerie J CarpenterDavid A Gewirtz
May 1, 2021·International Journal of Molecular Sciences·Sukhbir KaurDavid D Roberts
Apr 2, 2021·Journal of the National Cancer Institute·Pataje G PrasannaC Norman Coleman
Aug 28, 2021·Frontiers in Immunology·Mikel Etxebeste-MitxeltorenaBeatriz Martín-Antonio
Oct 23, 2021·Biology Open·Neylen Del ToroGerardo Ferbeyre

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Methods Mentioned

BETA
ELISA
FACS
flow cytometry
Flow
immunoprecipitation
PCR
protein assay

Clinical Trials Mentioned

NCT00630032

Software Mentioned

Quantity One
GSEA
SWATH
ImageJ

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