Cancer-Secreted miR-105 destroys vascular endothelial barriers to promote metastasis

Weiying Zhou, Miranda Y. Fong, Yongfen Min, George Somlo, Liang Liu, Melanie R. Palomares, Yang Yu, Amy Chow, Sean Timothy Francis O'Connor, Andrew R. Chin, Yun Yen, Yafan Wang, Eric G. Marcusson, Peiguo Chu, Jun Wu, Xiwei Wu, Arthur Xuejun Li, Zhuo Li, Hanlin Gao, Xiubao RenMark P. Boldin, Pengnian Charles Lin, Shizhen Emily Wang

Research output: Contribution to journalArticlepeer-review

618 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)501-515
Number of pages15
JournalCancer Cell
Volume25
Issue number4
DOIs
Publication statusPublished - Apr 14 2014
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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