Cell-in-Cell Death Is Not Restricted by Caspase-3 Deficiency in MCF-7 Cells.
Cell-in-Cell Death Is Not Restricted by Caspase-3 Deficiency in MCF-7 Cells.
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MCF-7 细胞中细胞内死亡不受 Caspase-3 缺陷的限制。
DOI：
10.4048/jbc.2016.19.3.231
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发表时间：
2016-09
影响因子：
2.4
通讯作者：
Tao A
中科院分区：
文献类型：
--
作者：
Wang S;He M;Li L;Liang Z;Zou Z;Tao A
细胞中细胞结构是由一个活细胞进入另一个同型或异型活细胞而产生的，这通常会导致内化细胞的死亡，特别是通过半胱氨酸蛋白酶依赖性细胞死亡（胚泡变性）或溶酶体依赖性细胞死亡（胞内变性）。虽然内陷引起了极大的关注，但其发生是有争议的，因为在其研究中使用的一种细胞系（MCF-7）缺乏caspase-3。我们使用MCF-7和A431细胞系研究了这个问题，这两种细胞系通常显示细胞中细胞的侵袭，并且具有不同水平的caspase-3表达。在两种细胞系中比较了细胞中细胞死亡形态、显微结构和信号通路。我们的结果证实MCF-7细胞是半胱天冬酶-3缺陷的，CASP-3基因部分缺失。这些细胞在星形孢菌素处理后经历缺乏典型凋亡特性的细胞死亡，而半胱天冬酶-3-充足的A431细胞显示典型的凋亡。caspase-3的存在既不与溶酶体依赖性，也不与caspase依赖性细胞中细胞死亡途径。然而，caspase-3的存在与转换从溶酶体依赖的细胞中细胞死亡的凋亡细胞中细胞死亡途径在胞内。此外，细胞缺氧，线粒体肿胀，细胞色素C的释放，和自噬过程中观察到内化的细胞。非半胱天冬酶依赖性内陷的发生不是细胞特异性过程。此外，内吞实际上代表了一种细胞自我修复系统，通过自噬发挥作用，以降解由细胞中细胞结构中的细胞缺氧引起的受损线粒体。然而，持续的自噬相关信号激活，而不减少细胞缺氧，最终导致溶酶体依赖性细胞内细胞死亡。
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. 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. 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. 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.
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影响因子：
4.8
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