title: Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis.
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.
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Deng
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Bai
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Likun
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Haiou
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Tianjin First Center Hospital, Tianjin 300192, China.
authors.forename: Jialu
authors.initials: J
authors.lastname: Li
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ning
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Dingzhi
authors.initials: D
authors.lastname: Huang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Guoguang
authors.initials: G
authors.lastname: Ying
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ba
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D066246:ErbB Receptors / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D066246:ErbB Receptors; D017228:Hepatocyte Growth Factor; D035683:MicroRNAs; D019859:Proto-Oncogene Proteins c-met; C066855:HGF protein, human; C528163:MIRN26 microRNA, human