In:
PLOS Biology, Public Library of Science (PLoS), Vol. 20, No. 10 ( 2022-10-24), p. e3001858-
Abstract:
Cancer cells survive chemotherapy and cause lethal relapse by entering a senescent state that facilitates expression of many phagocytosis/macrophage-related genes that engender a novel cannibalism phenotype. We used biosensors and live-cell imaging to reveal the basic steps and mechanisms of engulfment by senescent human and mouse tumor cells. We show filamentous actin in predator cells was localized to the prey cell throughout the process of engulfment. Biosensors to various phosphoinositide (PI) species revealed increased concentration and distinct localization of predator PI(4) P and PI(4,5)P2 at the prey cell during early stages of engulfment, followed by a transient burst of PI(3) P before and following internalization. PIK3C2B, the kinase responsible for generating PI(3)P, was required for complete engulfment. Inhibition or knockdown of Clathrin, known to associate with PIK3C2B and PI(4,5)P2, severely impaired engulfment. In sum, our data reveal the most fundamental cellular processes of senescent cell engulfment, including the precise localizations and dynamics of actin and PI species throughout the entire process.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001858
DOI:
10.1371/journal.pbio.3001858.g001
DOI:
10.1371/journal.pbio.3001858.g002
DOI:
10.1371/journal.pbio.3001858.g003
DOI:
10.1371/journal.pbio.3001858.g004
DOI:
10.1371/journal.pbio.3001858.g005
DOI:
10.1371/journal.pbio.3001858.g006
DOI:
10.1371/journal.pbio.3001858.g007
DOI:
10.1371/journal.pbio.3001858.s001
DOI:
10.1371/journal.pbio.3001858.s002
DOI:
10.1371/journal.pbio.3001858.s003
DOI:
10.1371/journal.pbio.3001858.s004
DOI:
10.1371/journal.pbio.3001858.s005
DOI:
10.1371/journal.pbio.3001858.s006
DOI:
10.1371/journal.pbio.3001858.s007
DOI:
10.1371/journal.pbio.3001858.s008
DOI:
10.1371/journal.pbio.3001858.s009
DOI:
10.1371/journal.pbio.3001858.s010
DOI:
10.1371/journal.pbio.3001858.s011
DOI:
10.1371/journal.pbio.3001858.s012
DOI:
10.1371/journal.pbio.3001858.s013
DOI:
10.1371/journal.pbio.3001858.s014
DOI:
10.1371/journal.pbio.3001858.s015
DOI:
10.1371/journal.pbio.3001858.s016
DOI:
10.1371/journal.pbio.3001858.s017
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2126773-X
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