The membrane-anchored MMP-regulator RECK is a target of myogenic regulatory factors

Michiko Echizenya1, Shunya Kondo, Rei Takahashi

  • 1Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Japan.

Oncogene
|July 12, 2005
PubMed

Insights

RECK protein suppresses muscle cell (myotube) formation. MyoD reduces RECK to aid myotube development, while MRF4 increases RECK for other muscle-building processes, highlighting RECK

Area of Science:

  • Molecular and Developmental Biology
  • Cancer Research
  • Muscle Development

Background:

  • The RECK protein, a regulator of matrix metalloproteinases, is downregulated in many solid tumors, correlating with poor prognosis.
  • Forced RECK expression in tumor cells inhibits angiogenesis, invasion, and metastasis.
  • Understanding RECK's role in normal development offers insights into tumor cell malignancy and control.

Purpose of the Study:

  • To investigate the role and regulation of the RECK gene during normal embryonic development, specifically in skeletal muscle.
  • To elucidate the relationship between RECK expression and key muscle development factors like MyoD and MRF4.

Main Methods:

  • Analysis of RECK expression patterns in later-stage wild-type mouse embryos.
  • Investigated RECK promoter activity in cultured cells in response to MyoD and MRF4.
  • Assessed myotube formation efficiency in myoblastic cells with varying RECK expression levels.

Main Results:

  • RECK is abundantly expressed in skeletal muscles of wild-type embryos, particularly where MRF4 is present.
  • MRF4 activates the RECK promoter, whereas MyoD suppresses it.
  • Absence of RECK enhances myotube formation efficiency, indicating RECK suppresses this process.

Conclusions:

  • MyoD downregulates RECK to promote myotube formation.
  • MRF4 upregulates RECK to support other aspects of myogenesis requiring extracellular matrix integrity.
  • RECK plays a dual role in myogenesis, balancing myotube formation with extracellular matrix maintenance.

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