Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival

In chemotherapy-treated breast cancer, wild-type p53 preferentially induces senescence over apoptosis, resulting in a persisting cell population constituting residual disease that drives relapse and poor patient survival via the senescence-associated secretory phenotype. Understanding the properties...

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Bibliographic Details
Published in:The Journal of cell biology 2019-11, Vol.218 (11), p.3827-3844
Main Authors: Tonnessen-Murray, Crystal A, Frey, Wesley D, Rao, Sonia G, Shahbandi, Ashkan, Ungerleider, Nathan A, Olayiwola, Joy O, Murray, Lucas B, Vinson, Benjamin T, Chrisey, Douglas B, Lord, Christopher J, Jackson, James G
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - pharmacology
Apoptosis
Breast cancer
Cell Proliferation - drug effects
Cell Survival - drug effects
Cellular Senescence - drug effects
Chemotherapy
Confocal microscopy
Dormancy
Doxorubicin - pharmacology
Gene expression
Humans
Macrophages
MCF-7 Cells
Mice
p53 Protein
Phenotypes
Senescence
Survival
Tumor cells
Tumor Cells, Cultured
Tumors
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Summary:In chemotherapy-treated breast cancer, wild-type p53 preferentially induces senescence over apoptosis, resulting in a persisting cell population constituting residual disease that drives relapse and poor patient survival via the senescence-associated secretory phenotype. Understanding the properties of tumor cells that allow survival after chemotherapy treatment is paramount. Using time-lapse and confocal microscopy to observe interactions of cells in treated tumors, we show here that chemotherapy-induced senescent cells frequently engulf both neighboring senescent or nonsenescent tumor cells at a remarkable frequency. Engulfed cells are processed through the lysosome and broken down, and cells that have engulfed others obtain a survival advantage. Gene expression analysis showed a marked up-regulation of conserved macrophage-like program of engulfment in chemotherapy-induced senescent cell lines and tumors. Our data suggest compelling explanations for how senescent cells persist in dormancy, how they manage the metabolically expensive process of cytokine production that drives relapse in those tumors that respond the worst, and a function for their expanded lysosomal compartment.
ISSN:0021-9525
1540-8140
DOI:10.1083/JCB.201904051