Synaptopodin-2 induces assembly of peripheral actin bundles and immature focal adhesions to promote lamellipodia formation and prostate cancer cell migration.
Synaptopodin-2 induces assembly of peripheral actin bundles and immature focal adhesions to promote lamellipodia formation and prostate cancer cell migration.
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DOI：
10.18632/oncotarget.3578
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发表时间：
2015-05-10
期刊：
影响因子：
--
通讯作者：
Duncan R
中科院分区：
文献类型：
--
作者：
Kai F;Fawcett JP;Duncan R
Synaptopodin-2 （Synpo2）是一种肌动蛋白结合蛋白和侵袭性癌症生物标志物，在细胞体中诱导复杂应激纤维网络的形成，促进PC3前列腺癌细胞在血清刺激下的迁移。这些肌动蛋白网络在增强癌细胞迁移中的作用尚不清楚。通过模拟和Synpo2转导的PC3细胞的时间过程分析和活细胞成像，我们现在发现Synpo2诱导肌动蛋白纤维在细胞周围的组装和arp2 /3依赖性板足的形成。板足以无方向性的方式形成或反复改变方向，解释了PC3细胞在血清刺激下的趋化动力学活性增强。肌球蛋白收缩促进前沿synpo2相关肌动蛋白丝的逆行流动，并与细胞体中的肌动蛋白网络合并。增强的PC3细胞迁移与synpo2诱导的板足和未成熟局灶粘连（FAs）的形成相关，但不依赖于肌球蛋白收缩或FA成熟。因此，先前报道的Synpo2诱导的应激纤维组装与增强的PC3细胞迁移之间的相关性反映了Synpo2作为一种新发现的肌动蛋白束形成和前缘细胞附近新生FA组装的调节剂的作用。
Synaptopodin-2 (Synpo2), an actin-binding protein and invasive cancer biomarker, induces formation of complex stress fiber networks in the cell body and promotes PC3 prostate cancer cell migration in response to serum stimulation. The role of these actin networks in enhanced cancer cell migration is unknown. Using time-course analysis and live cell imaging of mock- and Synpo2-transduced PC3 cells, we now show that Synpo2 induces assembly of actin fibers near the cell periphery and Arp2/3-dependent lamellipodia formation. Lamellipodia formed in a non-directional manner or repeatedly changed direction, explaining the enhanced chemokinetic activity of PC3 cells in response to serum stimulation. Myosin contraction promotes retrograde flow of the Synpo2-associated actin filaments at the leading edge and their merger with actin networks in the cell body. Enhanced PC3 cell migration correlates with Synpo2-induced formation of lamellipodia and immature focal adhesions (FAs), but is not dependent on myosin contraction or FA maturation. The previously reported correlation between Synpo2-induced stress fiber assembly and enhanced PC3 cell migration therefore reflects the role of Synpo2 as a newly identified regulator of actin bundle formation and nascent FA assembly near the leading cell edge.
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影响因子：
7.8
作者：
Nemethova, Maria;Auinger, Sonja;Small, J. Victor
通讯作者：
Small, J. Victor
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1083/jcb.200802081
发表时间：
2008-06-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fackler OT;Grosse R
通讯作者：
Grosse R
DOI：
10.1038/nrm2867
发表时间：
2010-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4
作者：
Kovac, Bianca;Teo, Jessica L.;Vallenius, Tea
通讯作者：
Vallenius, Tea