Modulation of E-Cadherin Function through the AmotL2 Isoforms Promotes Ameboid Cell Invasion.
Modulation of E-Cadherin Function through the AmotL2 Isoforms Promotes Ameboid Cell Invasion.
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通过AMOTL2同工型调节E-钙粘蛋白功能可促进运动细胞的侵袭。
DOI：
10.3390/cells12131682
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发表时间：
2023-06-21
期刊：
影响因子：
6
通讯作者：
Holmgren, Lars
中科院分区：
文献类型：
--
作者：
Subramani, Aravindh;Cui, Weiyingqi;Zhang, Yuanyuan;Friman, Tomas;Zhao, Zhihai;Huang, Wenmao;Fonseca, Pedro;Lui, Weng-Onn;Narayanan, Vani;Bobrowska, Justyna;Lekka, Malgorzata;Yan, Jie;Conway, Daniel E. E.;Holmgren, Lars
肿瘤细胞的扩散和远处转移的形成仍然是癌症患者死亡的主要原因。然而，控制细胞从微环境限制中释放的机制仍然不清楚。E-钙粘附素通过维持细胞与细胞之间的接触，负向控制上皮细胞的侵袭。此外，E-钙粘附素的失活会在体外触发侵袭。然而，E-钙粘蛋白的作用是复杂的，因为转移细胞维持E-钙粘蛋白的表达，这似乎对肿瘤细胞的生存有积极的作用。在这份报告中，我们提出了一种新的机制，描述了E-钙粘蛋白功能是如何被调节以促进侵袭的。我们以前已经证明E-钙粘素与p100AmotL2相关，p100AmotL2是放射状肌动蛋白形成和机械力传递所必需的。在这里，我们提出的证据是，p60AmotL2在侵袭性肿瘤细胞中表达，与p100AmotL2亚型结合，解偶联放射状肌动蛋白细丝的机械约束。我们首次发现E-钙粘蛋白通过p100AmotL2与肌动蛋白细胞骨架的偶联直接连接到核膜上。P60AmotL2的表达使这种连接失活，并改变了核层的性质，增强了细胞对细胞外基质微孔的侵袭。综上所述，我们认为两个AmotL2亚型的平衡在E-钙粘蛋白功能的调节中起重要作用，并且这个轴的不平衡促进了阿米巴细胞的侵袭。
The spread of tumor cells and the formation of distant metastasis remain the main causes of mortality in cancer patients. However, the mechanisms governing the release of cells from micro-environmental constraints remain unclear. E-cadherin negatively controls the invasion of epithelial cells by maintaining cell–cell contacts. Furthermore, the inactivation of E-cadherin triggers invasion in vitro. However, the role of E-cadherin is complex, as metastasizing cells maintain E-cadherin expression, which appears to have a positive role in the survival of tumor cells. In this report, we present a novel mechanism delineating how E-cadherin function is modulated to promote invasion. We have previously shown that E-cadherin is associated with p100AmotL2, which is required for radial actin formation and the transmission of mechanical force. Here, we present evidence that p60AmotL2, which is expressed in invading tumor cells, binds to the p100AmotL2 isoform and uncouples the mechanical constraint of radial actin filaments. We show for the first time that the coupling of E-cadherin to the actin cytoskeleton via p100AmotL2 is directly connected to the nuclear membrane. The expression of p60AmotL2 inactivates this connection and alters the properties of the nuclear lamina, potentiating the invasion of cells into micropores of the extracellular matrix. In summary, we propose that the balance of the two AmotL2 isoforms is important in the modulation of E-cadherin function and that an imbalance of this axis promotes ameboid cell invasion.
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DOI：
10.12703/p5-35
发表时间：
2013-09-02
期刊：
F1000prime reports
影响因子：
--
作者：
Budnar, Srikanth;Yap, Alpha S
通讯作者：
Yap, Alpha S
影响因子：
8
作者：
Bell ES;Shah P;Zuela-Sopilniak N;Kim D;Varlet AA;Morival JLP;McGregor AL;Isermann P;Davidson PM;Elacqua JJ;Lakins JN;Vahdat L;Weaver VM;Smolka MB;Span PN;Lammerding J
通讯作者：
Lammerding J
影响因子：
14.2
作者：
Groschwitz, Katherine R.;Hogan, Simon P.
通讯作者：
Hogan, Simon P.
DOI：
10.1016/j.bbamcr.2007.11.018
发表时间：
2008-03-01
影响因子：
5.1
作者：
Ernkvist, Mira;Birot, Olivier;Holmgren, Lars
通讯作者：
Holmgren, Lars
影响因子：
4.8
作者：
Chan, Siew Wee;Lim, Chun Jye;Hong, Wanjin
通讯作者：
Hong, Wanjin