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Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis
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Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis
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Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis
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Journal Article
Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis
2017
Overview
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.
EGFR signalling has been linked to cancer development but whether it has any role in pre-metastatic niche formation is not known. Here the authors show that gastric cancer cells send EGFR through exosomes to the liver where it causes the establishment of a favourable microenvironment thus promoting metastasis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
3' Untranslated Regions - genetics
/ 82/51
/ 82/80
/ 96/1
/ 96/35
/ 96/63
/ Cancer
/ Epidermal growth factor receptors
/ Exosomes
/ Gene Expression Regulation, Neoplastic
/ Hepatocyte Growth Factor - genetics
/ Hepatocyte Growth Factor - metabolism
/ Humanities and Social Sciences
/ Humans
/ Liver
/ Proto-Oncogene Proteins c-met - metabolism
/ Science
/ Soils
/ Stomach Neoplasms - genetics
/ Stomach Neoplasms - pathology
/ Tumors
