Sphingosine 1-phosphate transactivates c-Met as well as epidermal growth factor receptor (EGFR) in human gastric cancer cells.
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.
Shida
Dai
D
Department of Surgical Oncology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. SHIDA-DIS@h.u-tokyo.ac.jp
Kitayama
Joji
J
Yamaguchi
Hironori
H
Yamashita
Hiroharu
H
Mori
Ken
K
Watanabe
Toshiaki
T
Yatomi
Yutaka
Y
Nagawa
Hirokazu
H
D015153:Blotting, Western; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D011233:Precipitin Tests; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism*; D015533:Transcriptional Activation; D014443:Tyrosine / Q000378:metabolism
D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D014443:Tyrosine; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D013110:Sphingosine