Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis.

Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis.
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DOI:
10.1016/j.ccr.2014.03.007
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发表时间:
2014-04-14
期刊:
影响因子:
50.3
通讯作者:
Wang SE
Wang SE
中科院分区:
医学1区
文献类型:
--
作者:
Zhou W;Fong MY;Min Y;Somlo G;Liu L;Palomares MR;Yu Y;Chow A;O'Connor ST;Chin AR;Yen Y;Wang Y;Marcusson EG;Chu P;Wu J;Wu X;Li AX;Li Z;Gao H;Ren X;Boldin MP;Lin PC;Wang SE

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癌症分泌的miRNA是癌症-宿主串扰的新兴介质。在这里,我们表明,miR-105,这是典型的表达和分泌的转移性乳腺癌细胞,是一个有效的调节迁移通过靶向紧密连接蛋白ZO-1。在内皮细胞单层中,外来体介导的癌症分泌的miR-105的转移有效地破坏了紧密连接和这些天然屏障的完整性。非转移性癌细胞中miR-105的过表达会诱导远处器官的转移和血管渗透性,而高转移性肿瘤中miR-105的抑制会缓解这些影响。miR-105可在转移前阶段的循环中检测到,并且其在血液和肿瘤中的水平与早期乳腺癌中的ZO-1表达和转移进展相关。
Cancer-secreted miRNAs are emerging mediators of cancer–host crosstalk. Here we show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in non-metastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas inhibition of miR-105 in highly metastatic tumors alleviates these effects. MiR-105 can be detected in the circulation at the pre-metastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer.
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