Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival.
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Date
2019-11-04ICR Author
Author
Tonnessen-Murray, CA
Frey, WD
Rao, SG
Shahbandi, A
Ungerleider, NA
Olayiwola, JO
Murray, LB
Vinson, BT
Chrisey, DB
Lord, CJ
Jackson, JG
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Tumor Cells, Cultured
Animals
Humans
Mice
Doxorubicin
Antibiotics, Antineoplastic
Cell Proliferation
Cell Survival
MCF-7 Cells
Cellular Senescence
Research team
Gene Function
Language
eng
Date accepted
2019-08-12
License start date
2019-11
Citation
The Journal of cell biology, 2019, 218 (11), pp. 3827 - 3844
Publisher
ROCKEFELLER UNIV PRESS