Grb7 signal transduction protein mediates metastatic progression of esophageal carcinoma

Shinji Tanaka, Keishi Sugimachi, Hidetoshi Kawaguchi, Hiroshi Saeki, Shinji Ohno, Jack R. Wands, Keizo Sugimachi

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

We have previously reported the association of tumor cell invasion with expression of growth factor receptor-bound protein 7 (Grb7). This molecule contains a Src homology 2 (SH2) domain and shares structural homology with a cell migration molecule designated Mig-10 found in Caenorhabditis elegans. In the present study, Grb7 expression was analyzed in human esophageal carcinomas with or without metastatic spread. The Grb7 protein was overexpressed in 14 of 31 esophageal carcinomas as compared to the adjacent normal mucosa (45%) and this finding was significantly correlated with the presence of lymph node metastases. We also identified that Grb7 protein in esophageal carcinoma cells was phosphorylated on tyrosine by epidermal growth factor as well as attachment to extracellular matrix proteins including fibronectin. Such fibronectin-dependent phosphorylation of Grb7 was regulated by integrin signaling that leads to the interaction with focal adhesion kinase protein. Furthermore, ectopic expression of a Grb7-SH2 dominant- negative fragment inhibited the fibronectin-dependent phosphorylation of endogenous Grb7, and reduced migration of esophageal carcinoma cells into fibronectin. Our results suggest a role of Grb7 mediated signal transduction in generation of an invasive cell phenotype against extracellular matrix, and thus contributes to metastatic progression of human esophageal carcinoma. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)411-415
Number of pages5
JournalJournal of cellular physiology
Volume183
Issue number3
DOIs
Publication statusPublished - May 17 2000

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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