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Open Access Publications from the University of California

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

  • Author(s): Zhou, Weiying
  • Fong, Miranda Y.
  • Min, Yongfen
  • Somlo, George
  • Liu, Liang
  • Palomares, Melanie R.
  • Yu, Yang
  • Chow, Amy
  • O’Connor, Sean Francis
  • Chin, Andrew R.
  • Yen, Yun
  • Wang, Yafan
  • Marcusson, Eric G.
  • Chu, Peiguo
  • Wu, Jun
  • Wu, Xiwei
  • Li, Arthur Xuejun
  • Li, Zhuo
  • Gao, Hanlin
  • Ren, Xiubao
  • Boldin, Mark P.
  • Lin, Pengnian Charles
  • Wang, Shizhen Emily
  • et al.
Abstract

SUMMARYCancer-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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