Growth factor induction of cripto-1 shedding by glycosylphosphatidylinositol-phospholipase D and enhancement of endothelial cell migration

Kazuhide Watanabe, Caterina Bianco, Luigi Strizzi, Shin Hamada, Mario Mancino, Veronique Bailly, Wenjun Mo, Dingyi Wen, Konrad Miatkowski, Monica Gonzales, Michele Sanicola, Masaharu Seno, David S. Salomon

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Cripto-1 (CR-1) is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that has been shown to play an important role in embryogenesis and cellular transformation. CR-1 is reported to function as a membrane-bound co-receptor and as a soluble ligand. Although a number of studies implicate the role of CR-1 as a soluble ligand in tumor progression, it is unclear how transition from the membrane-bound to the soluble form is physiologically regulated and whether differences in biological activity exist between these forms. Here, we demonstrate that CR-1 protein is secreted from tumor cells into the conditioned medium after treatment with serum, epidermal growth factor, or lysophosphatidic acid, and this soluble form of CR-1 exhibits the ability to promote endothelial cell migration as a paracrine chemoattractant. On the other hand, membrane-bound CR-1 can stimulate endothelial cell sprouting through direct cell-cell interaction. Shedding of CR-1 occurs at the GPI-anchorage site by the activity of GPI-phospholipase D (GPI-PLD), because CR-1 shedding was suppressed by siRNA knockdown of GPI-PLD and enhanced by overexpression of GPI-PLD. These findings describe a novel molecular mechanism of CR-1 shedding, which may contribute to endothelial cell migration and possibly tumor angiogenesis.

Original languageEnglish
Pages (from-to)31643-31655
Number of pages13
JournalJournal of Biological Chemistry
Volume282
Issue number43
DOIs
Publication statusPublished - Oct 26 2007

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Phospholipase D
Glycosylphosphatidylinositols
Endothelial cells
Cell Movement
Intercellular Signaling Peptides and Proteins
Endothelial Cells
Tumors
Membranes
Ligands
Neoplasms
Chemotactic Factors
Membrane Glycoproteins
Conditioned Culture Medium
Bioactivity
Epidermal Growth Factor
Cell Communication
Small Interfering RNA
Embryonic Development
Cells
Serum

ASJC Scopus subject areas

  • Biochemistry

Cite this

Growth factor induction of cripto-1 shedding by glycosylphosphatidylinositol-phospholipase D and enhancement of endothelial cell migration. / Watanabe, Kazuhide; Bianco, Caterina; Strizzi, Luigi; Hamada, Shin; Mancino, Mario; Bailly, Veronique; Mo, Wenjun; Wen, Dingyi; Miatkowski, Konrad; Gonzales, Monica; Sanicola, Michele; Seno, Masaharu; Salomon, David S.

In: Journal of Biological Chemistry, Vol. 282, No. 43, 26.10.2007, p. 31643-31655.

Research output: Contribution to journalArticle

Watanabe, K, Bianco, C, Strizzi, L, Hamada, S, Mancino, M, Bailly, V, Mo, W, Wen, D, Miatkowski, K, Gonzales, M, Sanicola, M, Seno, M & Salomon, DS 2007, 'Growth factor induction of cripto-1 shedding by glycosylphosphatidylinositol-phospholipase D and enhancement of endothelial cell migration', Journal of Biological Chemistry, vol. 282, no. 43, pp. 31643-31655. https://doi.org/10.1074/jbc.M702713200
Watanabe, Kazuhide ; Bianco, Caterina ; Strizzi, Luigi ; Hamada, Shin ; Mancino, Mario ; Bailly, Veronique ; Mo, Wenjun ; Wen, Dingyi ; Miatkowski, Konrad ; Gonzales, Monica ; Sanicola, Michele ; Seno, Masaharu ; Salomon, David S. / Growth factor induction of cripto-1 shedding by glycosylphosphatidylinositol-phospholipase D and enhancement of endothelial cell migration. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 43. pp. 31643-31655.
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