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

Haiyang Zhang, Ting Deng, Rui Liu, Ming Bai, Likun Zhou, Xia Wang, Shuang Li, Xinyi Wang, Haiou Yang, Jialu Li, Tao Ning, Dingzhi Huang, Hongli Li, Le Zhang, Guoguang Ying () and Yi Ba ()
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Haiyang Zhang: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Ting Deng: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Rui Liu: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Ming Bai: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Likun Zhou: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Xia Wang: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Shuang Li: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Xinyi Wang: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Haiou Yang: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Jialu Li: Tianjin First Center Hospital
Tao Ning: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Dingzhi Huang: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Hongli Li: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Le Zhang: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Guoguang Ying: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer
Yi Ba: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms15016

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