Cell-in-Cell Death Is Not Restricted by Caspase-3 Deficiency in MCF-7 Cells.
10.4048/jbc.2016.19.3.231
- Author:
Shan WANG
1
;
Meifang HE
;
Linmei LI
;
Zhihua LIANG
;
Zehong ZOU
;
Ailin TAO
Author Information
1. The State Key Clinical Specialty in Allergy, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. taoailin@gzhmu.edu.cn
- Publication Type:Original Article
- Keywords:
Autophagy;
Caspase 3;
Cell hypoxia;
Entosis;
MCF-7 cells
- MeSH:
Apoptosis;
Autophagy;
Caspase 3*;
Cell Death;
Cell Hypoxia;
Cell Line;
Cytochromes c;
Entosis;
MCF-7 Cells*;
Mitochondria;
Mitochondrial Swelling;
Staurosporine
- From:Journal of Breast Cancer
2016;19(3):231-241
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Cell-in-cell structures are created by one living cell entering another homotypic or heterotypic living cell, which usually leads to the death of the internalized cell, specifically through caspase-dependent cell death (emperitosis) or lysosome-dependent cell death (entosis). Although entosis has attracted great attention, its occurrence is controversial, because one cell line used in its study (MCF-7) is deficient in caspase-3. METHODS: We investigated this issue using MCF-7 and A431 cell lines, which often display cell-in-cell invasion, and have different levels of caspase-3 expression. Cell-in-cell death morphology, microstructures, and signaling pathways were compared in the two cell lines. RESULTS: Our results confirmed that MCF-7 cells are caspase-3 deficient with a partial deletion in the CASP-3 gene. These cells underwent cell death that lacked typical apoptotic properties after staurosporine treatment, whereas caspase-3-sufficient A431 cells displayed typical apoptosis. The presence of caspase-3 was related neither to the lysosome-dependent nor to the caspase-dependent cell-in-cell death pathway. However, the existence of caspase-3 was associated with a switch from lysosome-dependent cell-in-cell death to the apoptotic cell-in-cell death pathway during entosis. Moreover, cellular hypoxia, mitochondrial swelling, release of cytochrome C, and autophagy were observed in internalized cells during entosis. CONCLUSION: The occurrence of caspase-independent entosis is not a cell-specific process. In addition, entosis actually represents a cellular self-repair system, functioning through autophagy, to degrade damaged mitochondria resulting from cellular hypoxia in cell-in-cell structures. However, sustained autophagy-associated signal activation, without reduction in cellular hypoxia, eventually leads to lysosome-dependent intracellular cell death.
