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      Phosphorylation of ephrin-B1 regulates dissemination of gastric scirrhous carcinoma.

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          Abstract

          Interaction of the Eph family of receptor protein tyrosine kinase and its ligand ephrin family induces bidirectional signaling via cell-cell contacts. High expression of B-type ephrin is frequently found in various cancer cells, and their expression levels are associated with high invasion of tumors and poor prognosis. However, whether ephrin-B1 actually promotes invasion of cancer cells in vivo has not been shown. We investigated the involvement of ephrin-B1 in regulating the invasiveness of scirrhous gastric cancer, which is a diffusely infiltrative carcinoma with high invasion potential. Reduction of ephrin-B1 expression by short inter-fering RNA or overexpression of phosphorylation-defective mutant suppressed migration and invasion of scirrhous gastric cancer cells in vitro without affecting tumor cell proliferation and apoptosis. Blocking of tyrosine phosphorylation of ephrin-B1 attenuates not only dissemination of cancer cells injected intraperitoneally but also local invasion and dissemination of orthotopically implanted cancer cells in the gastric wall of nude mice. Furthermore, blocking of ephrin-B1 phosphorylation attenuated the activation of Rac1 GTPase in these invasive gastric cancer cells. Our results suggest that tyrosine phosphorylation of ephrin-B1 promotes invasion of cancer cells in vivo and is a potential therapeutic target in some types of gastrointestinal cancers.

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          Author and article information

          Journal
          Am. J. Pathol.
          The American journal of pathology
          Elsevier BV
          0002-9440
          0002-9440
          Jul 2007
          : 171
          : 1
          Affiliations
          [1 ] Growth Factor Division, Central Animal Laboratory, National Cancer Center Research Institute, 5-1-1 Tsukiji, Tokyo, Japan.
          Article
          S0002-9440(10)61943-8
          10.2353/ajpath.2007.070033
          1941588
          17591954
          40d98163-f5ef-4ff0-bda8-3bc6905a5232

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