RECK

A novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodeling

Makoto Noda, Jun Seo Oh, Rei Takahashi, Shunya Kondo, Hitoshi Kitayama, Chiaki Takahashi

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

RECK was first isolated as a transformation suppressor gene by cDNA expression cloning in a mouse fibroblast cell line transformed by an activated RAS oncogene. Subsequently, reduced expression of RECK in transformed cells and cancer cells were demonstrated. Moreover, in several types of tumors, positive correlation between RECK expression and survival of patients have been noted. RECK encodes a GPI-anchored glycoprotein harboring three protease inhibitor-like domains. The RECK protein regulates at least three members of the matrix metalloproteinase (MMP) family, MMP-2, MMP-9, and MT1-MMP, in vitro or in cultured cells. Restored expression of RECK in cancer cell lines results in strong suppression of invasion, metastasis, and tumor angiogenesis. Mice lacking RECK die in utero with reduced integrity of blood vessels, the neural tube, and mesenchymal tissues. In these mice, MMP activity is elevated, and the amount of collagen type I greatly reduced. The RECK null phenotype is partially rescued (half day delay of death and marked recovery of tissue integrity) by MMP-2 null mutation, demonstrating functional interaction between RECK and MMP-2 in vivo and involvement of other target(s) for RECK in the lethal phenotype. These findings indicate that (i) RECK is an important regulator of extracellular matrix remodeling and that (ii) down-regulation of RECK by oncogenic signaling leads to the excessive activation of MMPs thereby promoting malignant behavior of cancer cells such as invasion, metastasis, and angiogenesis.

Original languageEnglish
Pages (from-to)167-175
Number of pages9
JournalCancer and Metastasis Reviews
Volume22
Issue number2-3
DOIs
Publication statusPublished - 2003 Jun 1
Externally publishedYes

Fingerprint

Extracellular Matrix
Matrix Metalloproteinase 2
Matrix Metalloproteinases
Neoplasms
Neoplasm Metastasis
Matrix Metalloproteinase 14
Suppressor Genes
Phenotype
Transformed Cell Line
Neural Tube
Matrix Metalloproteinase 9
Collagen Type I
Protease Inhibitors
Oncogenes
Blood Vessels
Organism Cloning
Cultured Cells
Glycoproteins
Down-Regulation
Complementary DNA

Keywords

  • Angiogenesis
  • ECM remodeling
  • MMP
  • Prognostic indicator
  • Protease inhibitor
  • RAS

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

RECK : A novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodeling. / Noda, Makoto; Oh, Jun Seo; Takahashi, Rei; Kondo, Shunya; Kitayama, Hitoshi; Takahashi, Chiaki.

In: Cancer and Metastasis Reviews, Vol. 22, No. 2-3, 01.06.2003, p. 167-175.

Research output: Contribution to journalArticle

Noda, Makoto ; Oh, Jun Seo ; Takahashi, Rei ; Kondo, Shunya ; Kitayama, Hitoshi ; Takahashi, Chiaki. / RECK : A novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodeling. In: Cancer and Metastasis Reviews. 2003 ; Vol. 22, No. 2-3. pp. 167-175.
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