TY - JOUR
T1 - Cancer-Secreted miR-105 destroys vascular endothelial barriers to promote metastasis
AU - Zhou, Weiying
AU - Fong, Miranda Y.
AU - Min, Yongfen
AU - Somlo, George
AU - Liu, Liang
AU - Palomares, Melanie R.
AU - Yu, Yang
AU - Chow, Amy
AU - O'Connor, Sean Timothy Francis
AU - Chin, Andrew R.
AU - Yen, Yun
AU - Wang, Yafan
AU - Marcusson, Eric G.
AU - Chu, Peiguo
AU - Wu, Jun
AU - Wu, Xiwei
AU - Li, Arthur Xuejun
AU - Li, Zhuo
AU - Gao, Hanlin
AU - Ren, Xiubao
AU - Boldin, Mark P.
AU - Lin, Pengnian Charles
AU - Wang, Shizhen Emily
N1 - Funding Information:
This work was supported by the City of Hope Women’s Cancer Program, National Institutes of Health (NIH)/National Cancer Institute (NCI) grants R01CA166020 (to S.E.W.) and R01CA163586 (to S.E.W.), California Breast Cancer Research Program grant 17IB-0054 (to S.E.W.), Breast Cancer Research Foundation-American Association for Cancer Research grant 12-60-26-WANG (to S.E.W.), and National Key Basic Research Development Program (973 Program) of China No. 2012CB9333004 (to X.R.). Research reported in this publication included work performed at core facilities supported by the NIH/NCI under grant P30CA33572. We thank the Center for Cancer Research, NCI, for funding support to P.C.L. We acknowledge Dr. Alan Fanning for kindly providing the ZO-1 plasmid. We also thank Drs. John Rossi, Hua Yu, John Shively, Linda Malkas, Andrew Raubitschek, Ren-Jang Lin, Michael Barish, Susan Kane, Shiuan Chen, and Joanne Mortimer for valuable comments as well as the City of Hope Core Facilities for highly professional services. G.S. had grant support from Celgene. E.G.M. was a full-time employee of a company developing miRNA therapeutics, Regulus Therapeutics.
PY - 2014/4/14
Y1 - 2014/4/14
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2014.03.007
DO - 10.1016/j.ccr.2014.03.007
M3 - Article
C2 - 24735924
AN - SCOPUS:84898476721
SN - 1535-6108
VL - 25
SP - 501
EP - 515
JO - Cancer Cell
JF - Cancer Cell
IS - 4
ER -
