title: Asialoglycoprotein receptor promotes cancer metastasis by activating the EGFR-ERK pathway.
abstract: Although the importance of glycans in malignant cell behavior is well documented, the potential involvement of endogenous lectins as modifiers of progression and metastasis in the tumor microenvironment has not been explored. In this study, we show that loss of the hepatic asialoglycoprotein receptor (ASGPR) in mice severely reduces the frequency of spontaneous lung metastasis after intrahepatic implantation of murine Lewis lung carcinoma (3LL) cells. Conversely, in vitro treatment with recombinant ASGPR increased the invasive and metastatic capacity of 3LL cells before intrahepatic implantation. ASGPR treatment in vitro increased the expression and production of matrix metalloproteinase-9 through activation of the epidermal growth factor receptor-extracellular signal-regulated kinase (EGFR-ERK) pathway. Our findings identify ASGPR as a novel important factor that responds to endogenous lectins in the tumor microenvironment to promote cancer metastasis by activating the EGFR-ERK pathway through interactions with counter-receptors on cancer cells.
authors.affiliation: Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Ueno
authors.forename: Marija
authors.initials: M
authors.lastname: Mojic
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Higashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Irimura
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000378:metabolism / Q000556:secondary*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D037263:Asialoglycoprotein Receptor; D066246:ErbB Receptors; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse