Nuclear fascin regulates cancer cell survival.
Nuclear fascin regulates cancer cell survival.
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DOI：
10.7554/elife.79283
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发表时间：
2022-08-30
期刊：
影响因子：
7.7
通讯作者：
Parsons, Maddy
中科院分区：
文献类型：
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作者：
Lawson, Campbell D.;Peel, Samantha;Jayo, Asier;Corrigan, Adam;Iyer, Preeti;Dalrymple, Mabel Baxter;Marsh, Richard J.;Cox, Susan;Van Audenhove, Isabel;Gettemans, Jan;Parsons, Maddy
Fascin是F-肌动蛋白捆绑的重要调节剂，从而导致丝状组装增强。在大多数实体瘤中，FASCIN也通过控制外围和核包膜的F-肌动蛋白结构来支持侵袭。最近，在广泛的细胞类型的细胞核中鉴定了Fascin，但核筋膜对癌细胞行为的贡献仍然未知。在这里，我们证明fascin在细胞核内捆绑F-肌动蛋白，以支持染色质组织和有效的DDR。 FASTIN与磷酸化的组蛋白H3直接相关，从而导致核筋膜的调节水平支持这些表型。通过表达核靶标特异性纳米体的表达或抑制组蛋白H3激酶会迫使核筋膜积累，从而增强和持续的核F-肌动蛋白捆绑，从而降低侵入性，侵入性和核筋膜特异性/驱动的凋亡。这些发现代表了Fascin可以支持肿瘤发生的另一种重要途径，并深入了解靶向fascin依赖性癌细胞杀死的潜在途径。
Fascin is an important regulator of F-actin bundling leading to enhanced filopodia assembly. Fascin is also overexpressed in most solid tumours where it supports invasion through control of F-actin structures at the periphery and nuclear envelope. Recently, fascin has been identified in the nucleus of a broad range of cell types but the contributions of nuclear fascin to cancer cell behaviour remain unknown. Here, we demonstrate that fascin bundles F-actin within the nucleus to support chromatin organisation and efficient DDR. Fascin associates directly with phosphorylated Histone H3 leading to regulated levels of nuclear fascin to support these phenotypes. Forcing nuclear fascin accumulation through the expression of nuclear-targeted fascin-specific nanobodies or inhibition of Histone H3 kinases results in enhanced and sustained nuclear F-actin bundling leading to reduced invasion, viability, and nuclear fascin-specific/driven apoptosis. These findings represent an additional important route through which fascin can support tumourigenesis and provide insight into potential pathways for targeted fascin-dependent cancer cell killing.
DOI：
10.1083/jcb.200709082
发表时间：
2008-03-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Pederson T
通讯作者：
Pederson T