title: Growth arrest-specific gene 6 and Axl signaling enhances gastric cancer cell survival via Akt pathway.
abstract: Activation of tyrosine kinases is an important factor during cancer development. Axl, one of the receptor tyrosine kinases, binds to the specific ligand growth arrest-specific gene 6 (Gas6), which encodes a vitamin K-dependent gamma-carboxyglutamyl protein. Although many receptor tyrosine kinases and their ligands are involved in gastric carcinogenesis, whether Gas6-Axl signaling is involved in gastric carcinogenesis has not been elucidated. The aim of this study was to investigate the expression of Gas6 and Axl in gastric cancer and also their roles during gastric carcinogenesis. mRNA and protein of Gas6 and Axl were highly expressed in a substantial proportion of human gastric cancer tissue and cell lines, and Gas6 expression was significantly associated with lymph node metastasis. With recombinant Gas6 and a decoy-receptor of Axl in vitro, we demonstrated that Gas6-Axl signaling pathway enhanced cellular survival and invasion and suppressed apoptosis via Akt pathway. Our results suggests that Gas6-Axl signaling plays a role during gastric carcinogenesis, and that targeting Gas6-Axl signaling could be a novel therapeutic for gastric cancer.
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tateo
authors.initials: T
authors.lastname: Sawabu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Seno
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kawashima
authors.forename: Akihisa
authors.initials: A
authors.lastname: Fukuda
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Uenoyama
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kawada
authors.forename: Naoki
authors.initials: N
authors.lastname: Kanda
authors.forename: Akira
authors.initials: A
authors.lastname: Sekikawa
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Fukui
authors.forename: Motoko
authors.initials: M
authors.lastname: Yanagita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshibayashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Satoh
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Sakai
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014812:Vitamin K / Q000494:pharmacology; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D020794:Receptor Protein-Tyrosine Kinases; D014812:Vitamin K; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C000722289:AXL protein, human