PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position.
PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position.
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DOI：
10.1242/jcs.190215
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发表时间：
2016-11-01
影响因子：
4
通讯作者：
Köhn M
中科院分区：
文献类型：
--
作者：
Luján P;Varsano G;Rubio T;Hennrich ML;Sachsenheimer T;Gálvez-Santisteban M;Martín-Belmonte F;Gavin AC;Brügger B;Köhn M
上皮结构的破坏是上皮肿瘤发生过程中的一个基本事件。我们发现，促癌磷酸酶PRL-3 （PTP4A3）在几种上皮癌中过表达，在极化上皮MDCK和Caco2细胞中表达，导致囊肿中侵袭和形成多个异位、完全极化的管腔。这两个过程都破坏上皮结构，是癌症的标志。这些发现的病理学相关性得到了在三维分支结构中生长的MCF-7乳腺癌细胞中内源性PRL-3的敲低的支持，显示了从多腔到单腔的分支末端的拯救。从机制上讲，以前的研究表明，异位管腔可能是由于有丝分裂纺锤体取向的丧失或不对称脱落的丧失而导致的中间体定位错误而产生的。在这里，我们发现PRL-3通过中间体错位触发异位管腔形成，而不改变纺锤体取向或不对称脱落，相反，PRL-3加速细胞分裂，这表明这一过程是MDCK囊肿异位管腔形成的另一种新机制。本文揭示的PRL-3对上皮结构的破坏是PRL-3促进癌症进展的新机制。摘要：促癌磷酸酶PRL-3通过加速细胞分裂，通过中体错位触发异位管腔形成，提示一种新的致癌机制。
Disruption of epithelial architecture is a fundamental event during epithelial tumorigenesis. We show that the expression of the cancer-promoting phosphatase PRL-3 (PTP4A3), which is overexpressed in several epithelial cancers, in polarized epithelial MDCK and Caco2 cells leads to invasion and the formation of multiple ectopic, fully polarized lumens in cysts. Both processes disrupt epithelial architecture and are hallmarks of cancer. The pathological relevance of these findings is supported by the knockdown of endogenous PRL-3 in MCF-7 breast cancer cells grown in three-dimensional branched structures, showing the rescue from multiple-lumen- to single-lumen-containing branch ends. Mechanistically, it has been previously shown that ectopic lumens can arise from midbodies that have been mislocalized through the loss of mitotic spindle orientation or through the loss of asymmetric abscission. Here, we show that PRL-3 triggers ectopic lumen formation through midbody mispositioning without altering the spindle orientation or asymmetric abscission, instead, PRL-3 accelerates cytokinesis, suggesting that this process is an alternative new mechanism for ectopic lumen formation in MDCK cysts. The disruption of epithelial architecture by PRL-3 revealed here is a newly recognized mechanism for PRL-3-promoted cancer progression. Summary: The cancer-promoting phosphatase PRL-3 triggers ectopic lumen formation through midbody mispositioning by accelerating cytokinesis, suggesting a new oncogenic mechanism.
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影响因子：
9.2
作者：
Kwon, Sang-Ho;Nedvetsky, Pavel I.;Mostov, Keith E.
通讯作者：
Mostov, Keith E.
影响因子：
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作者：
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影响因子：
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影响因子：
4
作者：
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通讯作者：
Echard, Arnaud
DOI：
10.1016/j.bbamcr.2007.11.004
发表时间：
2008-02-01
影响因子：
5.1
作者：
Forte, Eleonora;Orsatti, Laura;Tomei, Licia
通讯作者：
Tomei, Licia