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Growth arrest‐specific gene 6 and Axl signaling enhances gastric cancer cell survival via Akt pathway
Author(s) -
Sawabu Tateo,
Seno Hiroshi,
Kawashima Tomoko,
Fukuda Akihisa,
Uenoyama Yoshito,
Kawada Mayumi,
Kanda Naoki,
Sekikawa Akira,
Fukui Hirokazu,
Yanagita Motoko,
Yoshibayashi Hiroshi,
Satoh Seiji,
Sakai Yoshiharu,
Nakano Toru,
Chiba Tsutomu
Publication year - 2007
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20211
Subject(s) - gas6 , receptor tyrosine kinase , axl receptor tyrosine kinase , biology , cancer research , carcinogenesis , protein kinase b , cancer , signal transduction , receptor protein tyrosine kinases , tyrosine kinase , microbiology and biotechnology , jak stat signaling pathway , genetics
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 γ‐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. © 2006 Wiley‐Liss, Inc.