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Cell-in-Cell Death Is Not Restricted by Caspase-3 Deficiency in MCF-7 Cells / 한국유방암학회지
Journal of Breast Cancer ; : 231-241, 2016.
Article in English | WPRIM | ID: wpr-201280
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Autophagy / Cell Hypoxia / Cell Line / Cell Death / Apoptosis / Staurosporine / Cytochromes c / Caspase 3 / Entosis / MCF-7 Cells Language: English Journal: Journal of Breast Cancer Year: 2016 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Autophagy / Cell Hypoxia / Cell Line / Cell Death / Apoptosis / Staurosporine / Cytochromes c / Caspase 3 / Entosis / MCF-7 Cells Language: English Journal: Journal of Breast Cancer Year: 2016 Type: Article