Consecutive entosis stages in human substrate-dependent cultured cells.
Consecutive entosis stages in human substrate-dependent cultured cells.
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DOI：
10.1038/s41598-017-12867-6
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发表时间：
2017-10-02
影响因子：
4.6
通讯作者：
Onishchenko GE
中科院分区：
文献类型：
--
作者：
Garanina AS;Kisurina-Evgenieva OP;Erokhina MV;Smirnova EA;Factor VM;Onishchenko GE
内吞，即细胞侵入另一个细胞而死亡，是肿瘤上皮细胞的典型特征。细胞中细胞结构的形成在悬浮培养中得到了广泛的研究，但在底物依赖的细胞中仍然知之甚少。在这里，我们使用电子显微镜、共聚焦显微镜和延时显微镜结合细胞内成分的药物抑制来研究两种依赖底物的人肿瘤培养物A431和MCF7的内吞动力学。总而言之，我们鉴定和表征了五个连续的齿槽突起阶段，这在两个被检查的细胞系中都是常见的。我们进一步证明了肌动蛋白细丝在齿槽突起和侵入细胞中起着至关重要的作用。内生细胞的微管和高尔基体提供了入侵细胞内化所需的膜扩张。微丝和微管的解聚和高尔基复合体的解体抑制了牙本质的形成。我们证实了粘连连接的存在，并发现在入侵细胞和内生细胞之间形成了桥粒。内化的细胞由于溶酶体的激活而降解，而高尔基体的解体不影响这一过程。因此，在底物依赖的培养中，齿状突需要微丝、微管和高尔基复合体才能侵袭细胞，而不是内化细胞降解。
Entosis, or cell death by invading another cell, is typical for tumor epithelial cells. The formation of cell-in-cell structures is extensively studied in suspension cultures, but remains poorly understood in substrate-dependent cells. Here, we used electron, confocal and time-lapse microscopy in combination with pharmacological inhibition of intracellular components to study the kinetics of entosis using two human substrate-dependent tumor cultures, A431 and MCF7. In total, we identified and characterized five consecutive stages of entosis, which were common for both examined cell lines. We further demonstrated that actin filaments in the entotic as well as invading cells were crucial for entosis. Microtubules and the Golgi apparatus of entotic cells provided membrane expansion required for internalization of the invading cell. Depolymerization of microfilaments and microtubules, and disintegration of the Golgi complex inhibited entosis. We confirmed the presence of adhesive junctions and discovered the formation of desmosomes between the invading and entotic cells. The internalized cell was shown to be degraded due to the lysosomal activation in both cells whereas the disintegration of the Golgi apparatus did not affect the process. Thus, in the substrate-dependent cultures, entosis requires microfilaments, microtubules and the Golgi complex for cell invasion, but not for internalized cell degradation.
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锚固的丧失主要诱导非典型局灶性粘附激酶信号下人类乳腺上皮细胞系中的非凋亡细胞死亡。
影响因子：
9
作者：
Ishikawa F;Ushida K;Mori K;Shibanuma M
通讯作者：
Shibanuma M
影响因子：
13.3
作者：
Florey, Oliver;Gammoh, Noor;Overholtzer, Michael
通讯作者：
Overholtzer, Michael
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
4
作者：
Guadamillas, Marta C.;Cerezo, Ana;del Pozo, Miguel A.
通讯作者：
del Pozo, Miguel A.
影响因子：
3.3
作者：
Cole, NB;Sciaky, N;LippincottSchwartz, J
通讯作者：
LippincottSchwartz, J