- Zhou, Weiying;
- Fong, Miranda Y;
- Min, Yongfen;
- Somlo, George;
- Liu, Liang;
- Palomares, Melanie R;
- Yu, Yang;
- Chow, Amy;
- O’Connor, Sean Timothy 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
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.