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

First Author  Zhang H Year  2017
Journal  Nat Commun Volume  8
Pages  15016 PubMed ID  28393839
Mgi Jnum  J:250348 Mgi Id  MGI:5921848
Doi  10.1038/ncomms15016 Citation  Zhang H, et al. (2017) Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis. Nat Commun 8:15016
abstractText  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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