Growth arrest-specific gene 6 and Axl signaling enhances gastric cancer cell survival via Akt pathway.
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.
Sawabu
Tateo
T
Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Seno
Hiroshi
H
Kawashima
Tomoko
T
Fukuda
Akihisa
A
Uenoyama
Yoshito
Y
Kawada
Mayumi
M
Kanda
Naoki
N
Sekikawa
Akira
A
Fukui
Hirokazu
H
Yanagita
Motoko
M
Yoshibayashi
Hiroshi
H
Satoh
Seiji
S
Sakai
Yoshiharu
Y
Nakano
Toru
T
Chiba
Tsutomu
T
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
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