J Breast Cancer.  2016 Sep;19(3):231-241. 10.4048/jbc.2016.19.3.231.

Cell-in-Cell Death Is Not Restricted by Caspase-3 Deficiency in MCF-7 Cells

• Wang S
• He M
• Li L
• Liang Z
• Zou Z
• Tao A

• KMID: 2413947
• DOI: http://doi.org/10.4048/jbc.2016.19.3.231

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.

Keyword

Autophagy; Caspase 3; Cell hypoxia; Entosis; MCF-7 cells

MeSH Terms

Apoptosis
Autophagy
Caspase 3*
Cell Death
Cell Hypoxia
Cell Line
Cytochromes c
Entosis
MCF-7 Cells*
Mitochondria
Mitochondrial Swelling
Staurosporine
Caspase 3
Cytochromes c
Staurosporine

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