UCH-L1 promotes invasion of breast cancer cells through activating Akt signaling pathway.
UCH-L1 promotes invasion of breast cancer cells through activating Akt signaling pathway.
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DOI：
10.1002/jcb.26232
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发表时间：
2018-01
影响因子：
4
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Luo Y;He J;Yang C;Orange M;Ren X;Blair N;Tan T;Yang JM;Zhu H
作为一种去泛素化酶，泛素C-末端水解酶（UCH）-L1已被证明在几种人类癌症中过表达。然而，UCH-L1在乳腺癌侵袭中的功能仍不清楚。在这里，我们报告了UCH-L1的表达在具有较高侵袭能力的癌细胞中显著较高。虽然异位UCH-L1表达未能改变MCF-7细胞的细胞增殖，但它引起了细胞侵袭的显著上调。此外，siRNA介导的UCH-L1敲低导致UCH-L1过表达MCF-7细胞中的侵袭抑制。为了确定这些观察结果背后的分子机制，通过将UCH-L1蛋白与细菌生物素连接酶（E. coli BirA R118G，BioID）。链霉亲和素磁珠下拉实验显示UCH-L1在MCF-7细胞中可与Akt相互作用。用His标记的重组UCH-L1蛋白和来自MCF-7细胞的细胞裂解物的下拉测定进一步证明UCH-L1优先结合Akt 2以激活Akt。最后，我们证明了UCH-L1的过表达导致Akt的激活，这通过磷酸化Akt的上调来证明。因此，这些发现表明UCH-L1促进乳腺癌细胞的侵袭，并可能作为治疗乳腺癌患者的潜在治疗靶点。
As a de-ubiquitin enzyme, ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to be overexpressed in several human cancers. However, the function of UCH-L1 in invasion of breast cancers is still unclear. Here we report that the expression of UCH-L1 is significantly higher in cancer cells with higher invasive ability. While ectopic UCH-L1 expression failed to alter cell proliferation in MCF-7 cells, it caused a significant upregulation of cellular invasion. Furthermore, siRNA mediated knockdown of UCH-L1 led to suppression of invasion in UCH-L1 overexpressing MCF-7 cells. In order to identify molecular mechanisms underlying these observations, a novel in vitro proximity-dependent biotin identification method was developed by fusing UCH-L1 protein with a bacterial biotin ligase (E. coli BirA R118G, BioID). Streptavidin magnetic beads pulldown assay revealed that UCH-L1 can interact with Akt in MCF-7 cells. Pulldown assay with His tagged recombinant UCH-L1 protein and cell lysate from MCF-7 cells further demonstrated that UCH-L1 preferentially binds to Akt2 for Akt activation. Finally, we demonstrated that overexpression of UCH-L1 led to activation of Akt as evidenced by upregulation of phosphorylated Akt. Thus, these findings demonstrated that UCH-L1 promotes invasion of breast cancer cells and might serve as a potential therapeutic target for treatment of human patients with breast cancers.
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影响因子：
3.9
作者：
Jin C;Yu W;Lou X;Zhou F;Han X;Zhao N;Lin B
通讯作者：
Lin B
影响因子：
11.4
作者：
通讯作者：
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影响因子：
8
作者：
Hui, L.;Zheng, Y.;Foster, D. A.
通讯作者：
Foster, D. A.
影响因子：
4.8
作者：
Choi, J;Levey, AI;Li, L
通讯作者：
Li, L
DOI：
10.1073/pnas.0911516107
发表时间：
2010-01-26
影响因子：
11.1
作者：
Chen, Fujun;Sugiura, Yoshie;Lin, Weichun
通讯作者：
Lin, Weichun