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Sphingosine 1‐phosphate transactivates c‐Met as well as epidermal growth factor receptor (EGFR) in human gastric cancer cells
Author(s) -
Shida Dai,
Kitayama Joji,
Yamaguchi Hironori,
Yamashita Hiroharu,
Mori Ken,
Watanabe Toshiaki,
Yatomi Yutaka,
Nagawa Hirokazu
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.10.024
Subject(s) - transactivation , epidermal growth factor receptor , receptor tyrosine kinase , sphingosine 1 phosphate , cancer research , sphingosine , g protein coupled receptor , ror1 , phosphorylation , tyrosine kinase , cancer , growth factor receptor , epidermal growth factor , biology , chemistry , receptor , signal transduction , microbiology and biotechnology , platelet derived growth factor receptor , medicine , growth factor , biochemistry , transcription factor , gene
Receptor tyrosine kinases (RTKs) are transactivated by the stimulation of G protein‐coupled receptors (GPCRs). Sphingosine 1‐phosphate (S1P), a ligand of GPCR, is known as a tumor‐promoting lipid, but its signaling pathways are not fully understood. We here demonstrated that S1P induces rapid and transient tyrosine phosphorylation of epidermal growth factor receptor (EGFR) and c‐Met in gastric cancer cells, both of which have been proposed as prognostic markers of gastric cancers. The pathway of S1P‐induced c‐Met transactivation is Gi‐independent and matrix metalloproteinase‐independent, which differs from that of EGFR transactivation. Our results indicate that S1P acts upstream of various RTKs and thus may act as a potent stimulator of gastric cancer.