Cancer-Secreted miR-105 Destroys Vascular Endothelial Barriers to Promote Metastasis

被引：1296

作者：

Zhou, Weiying ^{[1
,13
]}

Fong, Miranda Y. ^{[1
]}

Min, Yongfen ^{[17
]}

Somlo, George ^{[2
]}

Liu, Liang ^{[1
,14
,15
]}

Palomares, Melanie R. ^{[2
,3
]}

Yu, Yang ^{[1
,14
,15
]}

Chow, Amy ^{[1
]}

O'Connor, Sean Timothy Francis ^{[1
]}

Chin, Andrew R. ^{[1
,12
]}

Yen, Yun ^{[4
,9
]}

Wang, Yafan ^{[9
]}

Marcusson, Eric G. ^{[16
]}

Chu, Peiguo ^{[5
]}

Wu, Jun ^{[6
]}

Wu, Xiwei ^{[10
]}

Li, Arthur Xuejun ^{[7
]}

Li, Zhuo ^{[11
]}

Gao, Hanlin ^{[1
,10
]}

Ren, Xiubao ^{[14
,15
]}

Boldin, Mark P. ^{[8
]}

Lin, Pengnian Charles ^{[17
]}

Wang, Shizhen Emily ^{[1
]}

机构：

[1] City Hope Beckman Res Inst & Med Ctr, Dept Canc Biol, Duarte, CA 91010 USA

[2] City Hope Beckman Res Inst & Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA

[3] City Hope Beckman Res Inst & Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA

[4] City Hope Beckman Res Inst & Med Ctr, Dept Mol Pharmacol, Duarte, CA 91010 USA

[5] City Hope Beckman Res Inst & Med Ctr, Dept Pathol, Duarte, CA 91010 USA

[6] City Hope Beckman Res Inst & Med Ctr, Dept Comparat Med, Duarte, CA 91010 USA

[7] City Hope Beckman Res Inst & Med Ctr, Dept Informat Sci, Duarte, CA 91010 USA

[8] City Hope Beckman Res Inst & Med Ctr, Dept Mol & Cellular Biol, Duarte, CA 91010 USA

[9] City Hope Beckman Res Inst & Med Ctr, Core Translat Res Lab, Duarte, CA 91010 USA

[10] City Hope Beckman Res Inst & Med Ctr, Core Integrat Genom, Duarte, CA 91010 USA

[11] City Hope Beckman Res Inst & Med Ctr, Core Electron Microscopy, Duarte, CA 91010 USA

[12] City Hope Irell & Manella Grad Sch Biol Sci, Duarte, CA 91010 USA

[13] Third Mil Med Univ, Coll Pharm, Dept Pharmacol, Chongqing 400038, Peoples R China

[14] Tianjin Med Univ Canc Inst & Hosp, Dept Biotherapy, Tianjin 300060, Peoples R China

[15] Tianjin Med Univ Canc Inst & Hosp, Key Lab Canc Immunol, Tianjin 300060, Peoples R China

[16] Regulus Therapeut, Oncol & Basic Mech, San Diego, CA 92121 USA

[17] NCI, Ctr Canc Res, Frederick, MD 21702 USA

来源：

CANCER CELL | 2014年 / 25卷 / 04期

基金：

美国国家卫生研究院;

关键词：

ADVANCED BREAST-CANCER; BLOOD-BASED MARKERS; CIRCULATING MICRORNAS; CELL-MIGRATION; DIAGNOSTIC BIOMARKERS; TIGHT JUNCTIONS; SMALL GTPASES; IN-SITU; EXOSOMES; EXPRESSION;

D O I：

10.1016/j.ccr.2014.03.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cancer-secreted microRNAs (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 nonmetastatic 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 premetastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer.

引用

页码：501 / 515

页数：15

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