title: Cell-in-Cell Death Is Not Restricted by Caspase-3 Deficiency in MCF-7 Cells.
abstract: OBJECTIVE
  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 theCASP-3gene. 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The State Key Clinical Specialty in Allergy, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China.; The State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Meifang
authors.initials: M
authors.lastname: He
authors.affiliation: The State Key Clinical Specialty in Allergy, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China.; The State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
authors.forename: Linmei
authors.initials: L
authors.lastname: Li
authors.affiliation: The State Key Clinical Specialty in Allergy, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China.; The State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liang
authors.affiliation: The State Key Clinical Specialty in Allergy, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China.; The State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
authors.forename: Zehong
authors.initials: Z
authors.lastname: Zou
authors.affiliation: The State Key Clinical Specialty in Allergy, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China.; The State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
authors.forename: Ailin
authors.initials: A
authors.lastname: Tao
keywords: Autophagy; Caspase 3; Cell hypoxia; Entosis; MCF-7 cells