Intracellular CD24 Inhibits Cell Invasion by Posttranscriptional Regulation of BART through Interaction with G3BP
Intracellular CD24 Inhibits Cell Invasion by Posttranscriptional Regulation of BART through Interaction with G3BP
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DOI：
10.1158/0008-5472.can-10-2743
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发表时间：
2011-02-01
期刊：
影响因子：
11.2
通讯作者：
Hollingsworth, Michael A.
中科院分区：
文献类型：
--
作者：
Taniuchi, Keisuke;Nishimori, Isao;Hollingsworth, Michael A.
我们报告了 CD24 分子在胰腺癌细胞中的新功能。细胞内 CD24 与应激颗粒相关，应激颗粒含有调节 mRNA 稳定性和翻译的特定 mRNA 和 RNA 结合蛋白。应激颗粒中的细胞内 CD24 与 G3BP（一种磷酸化依赖性核糖核酸内切酶）相关。 CD24/G3BP 复合物定位的囊泡被运输至迁移细胞中的细胞突起。我们发现 G3BP 结合并降解 Arl 二结合物 (BART) mRNA。 BART 最初被确定为 ARL2 的结合伴侣，ARL2 是一种小 G 蛋白，被认为是微管动力学和折叠的调节因子。细胞内 CD24 抑制应激颗粒中 G3BP 对 BART mRNA 的特异性核糖核酸内切酶活性。我们发现，在原位异种移植模型中，CD24 的敲低会增加胰腺癌细胞的腹膜后侵袭和肝转移，并且 BART 还可以预防胰腺癌细胞的腹膜后侵袭和肝转移。我们的结果表明表面CD24可能在抑制细胞侵袭和转移中发挥作用，而细胞内CD24通过G3BP RNase活性影响BART mRNA水平的转录后调节来抑制侵袭和转移。癌症研究； 71(3)； 895-905。 (C)2011 AACR。
We report a novel function for the CD24 molecule in pancreatic cancer cells. Intracellular CD24 is associated with stress granules that contain specific mRNAs and RNA-binding proteins that regulate mRNA stability and translation. Intracellular CD24 in stress granules is associated with G3BP, a phosphorylation-dependent endoribonuclease. The vesicles in which the CD24/G3BP complex localizes are transported toward cell protrusions in migrating cells. We show that G3BP binds to and degrades Binder of Arl Two (BART) mRNA. BART was originally identified as a binding partner of ARL2, a small G-protein implicated as a regulator of microtubule dynamics and folding. Intracellular CD24 inhibits the specific endoribonuclease activity of G3BP toward BART mRNA in stress granules. We show that knockdown of CD24 increases retroperitoneal invasion and liver metastasis of pancreatic cancer cells in an orthotopic xenograft model, and that BART also prevents retroperitoneal invasion and liver metastasis of pancreatic cancer cells. Our results imply that surface CD24 may play a role in the inhibition of cell invasion and metastasis, and that intracellular CD24 inhibits invasiveness and metastasis through its influence on the posttranscriptional regulation of BART mRNA levels via G3BP RNase activity. Cancer Res; 71(3); 895-905. (C)2011 AACR.