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Nat Commun. 2017 Apr 10;8:15016. doi: 10.1038/ncomms15016.

Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis.

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Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
Department of Gastroenterology, Tianjin First Center Hospital, Tianjin 300192, China.


The metastatic organotropism has been one of the cancer's greatest mysteries since the 'seed and soil' hypothesis. Although the role of EGFR in cancer cells is well studied, the effects of secreted EGFR transported by exosomes are less understood. Here we show that EGFR in exosomes secreted from gastric cancer cells can be delivered into the liver and is integrated on the plasma membrane of liver stromal cells. The translocated EGFR is proved to effectively activate hepatocyte growth factor (HGF) by suppressing miR-26a/b expression. Moreover, the upregulated paracrine HGF, which binds the c-MET receptor on the migrated cancer cells, provides fertile 'soil' for the 'seed', facilitating the landing and proliferation of metastatic cancer cells. Thus, we propose that EGFR-containing exosomes derived from cancer cells could favour the development of a liver-like microenvironment promoting liver-specific metastasis.

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