Arf6 and its ZEB1-EPB41L5 mesenchymal axis are required for both mesenchymal- and amoeboid-type invasion of cancer cells.
Arf6 and its ZEB1-EPB41L5 mesenchymal axis are required for both mesenchymal- and amoeboid-type invasion of cancer cells.
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DOI：
10.1080/21541248.2016.1249043
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发表时间：
2018-09-03
期刊：
影响因子：
--
通讯作者：
Sabe H
中科院分区：
文献类型：
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作者：
Handa H;Hashimoto A;Hashimoto S;Sabe H
肿瘤侵袭的方式在间叶型和阿米巴样型之间转换，以响应微环境，其中RhoA和rac1被选择性地要求执行不同的肌动蛋白-细胞骨架重塑模式。膜重塑是侵袭的另一个组成部分。ARF6调节细胞外周分子的循环，在恶性肿瘤中经常与其效应因子AMAP1/ASAP1/DDEF1一起过度表达。当AMAP1与ZEB1诱导的间充质特异性蛋白EPB41L5结合时，这一途径促进了间叶型侵袭。在这里，我们表明，Arf6-AMAP1-EPB41L5途径和ZEB1，也是关键的阿米巴类型的入侵，通过受体酪氨酸激酶和G蛋白偶联受体信号。因此，Arf6似乎对RhoA和rac1驱动的癌症侵袭都是必要的。此外，阿米巴样癌的侵袭可能需要在癌细胞内激活某种类型的间充质程序。
Modes of cancer invasion interchange between the mesenchymal type and amoeboid type in response to the microenvironment, in which RhoA and Rac1 are selectively required to perform different modes of actin-cytoskeletal remodeling. Membrane remodeling is another integral part of invasion. Arf6 regulates the recycling of molecules at the cell periphery, and is often overexpressed in malignant cancers together with its effector AMAP1/ASAP1/DDEF1. This pathway promotes mesenchymal-type invasion when AMAP1 binds to EPB41L5, a mesenchymal-specific protein induced by ZEB1. Here we show that the Arf6-AMAP1-EPB41L5 pathway, and ZEB1, are also crucial for amoeboid-type invasion, via receptor tyrosine kinase and G-protein-coupled receptor signaling. Thus, Arf6 appears to be necessary for both RhoA- and Rac1-driven cancer invasion. Moreover, amoeboid-type cancer invasion may require the activation of some type of mesenchymal program within the cancer cells.