TRAIL signaling promotes entosis in colorectal cancer.
TRAIL signaling promotes entosis in colorectal cancer.
复制标题
DOI：
10.1083/jcb.202010030
复制
发表时间：
2021-11-01
期刊：
影响因子：
--
通讯作者：
Prehn JHM
中科院分区：
文献类型：
--
作者：
Bozkurt E;Düssmann H;Salvucci M;Cavanagh BL;Van Schaeybroeck S;Longley DB;Martin SJ;Prehn JHM
Bozkurt等人发现，除了激活凋亡外，TRAIL信号还通过TRAIL受体和caspase-8的结构存在而非催化活性诱导结肠癌细胞内倾。此外，它们为CRC中TRAIL信号、细胞内结构和临床结果的关联提供了证据。内吞是一个活细胞进入另一个活细胞的非吞噬细胞间相互作用的一种形式。肿瘤表现为内吞；然而，控制内毒素的因素仍有待阐明。本研究发现，除了诱导细胞凋亡外，TRAIL信号还是结肠癌细胞内吞的有效激活因子。凋亡和内吞的启动都需要TRAIL受体DR4和DR5；然而，凋亡和内吞的诱导在caspase-8上是不同的，因为它的结构存在足以诱导内吞而不是凋亡。虽然凋亡和内吞在形态和生化上是不同的，但敲除Bax和Bak或抑制caspase也会抑制内吞细胞死亡，促进内细胞的存活和释放。对结直肠癌肿瘤的分析揭示了TRAIL信号和CIC结构之间的显著关联。最后，结直肠肿瘤侵袭性前部存在CIC结构与患者不良预后密切相关。
Bozkurt et al. find that besides activating apoptosis, TRAIL signaling induces entosis in colon cancer cells through TRAIL receptors and structural presence but not catalytic activity of caspase-8. Moreover, they provide evidence for an association of TRAIL signaling, cell-in-cell structures, and clinical outcome in CRC. Entosis is a form of nonphagocytic cell-in-cell (CIC) interaction where a living cell enters into another. Tumors show evidence of entosis; however, factors controlling entosis remain to be elucidated. Here, we find that besides inducing apoptosis, TRAIL signaling is a potent activator of entosis in colon cancer cells. Initiation of both apoptosis and entosis requires TRAIL receptors DR4 and DR5; however, induction of apoptosis and entosis diverges at caspase-8 as its structural presence is sufficient for induction of entosis but not apoptosis. Although apoptosis and entosis are morphologically and biochemically distinct, knockout of Bax and Bak, or inhibition of caspases, also inhibits entotic cell death and promotes survival and release of inner cells. Analysis of colorectal cancer tumors reveals a significant association between TRAIL signaling and CIC structures. Finally, the presence of CIC structures in the invasive front regions of colorectal tumors shows a strong correlation with adverse patient prognosis.
登录
查看更多内容
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
5.8
作者：
Brooks, AD;Sayers, TJ
通讯作者：
Sayers, TJ
影响因子：
4.6
作者：
Garanina AS;Kisurina-Evgenieva OP;Erokhina MV;Smirnova EA;Factor VM;Onishchenko GE
通讯作者：
Onishchenko GE
影响因子：
2
作者：
Flusberg, Deborah A.;Sorger, Peter K.
通讯作者：
Sorger, Peter K.
影响因子：
3.3
作者：
Flusberg DA;Roux J;Spencer SL;Sorger PK
通讯作者：
Sorger PK