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ROME, an Ancient Gene with a Novel Function in Vertebrates, Is a Key Modulator of Embryonal Development and Cancer

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  • 1Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia.

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Regulator of Metastasis (ROME) drives cancer metastasis by interacting with beta-catenin and vimentin. This protein is critical for development and its elevated expression correlates with poorer patient survival in multiple cancers.

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cancer Research

Background:

  • INAFM2, a predicted membrane protein, has an unknown function in vertebrates.
  • A genome-wide screen identified INAFM2 as a key regulator of metastasis.

Purpose of the Study:

  • To investigate the function of INAFM2, proposing the name Regulator of Metastasis (ROME).
  • To elucidate ROME's role in development, metastasis, and its molecular mechanisms.

Main Methods:

  • Genome-wide transcriptional activation screen in vivo.
  • Subcellular localization and posttranslational modification analysis.
  • Zebrafish and immunodeficient mouse models for metastasis studies.
  • Western blot and co-immunoprecipitation assays.

Main Results:

  • ROME negatively regulates the Wnt pathway by binding beta-catenin.
  • Blocking ROME in zebrafish causes developmental defects, reversible by Wnt inhibition.
  • ROME enhances cancer cell motility, invasion, and metastasis in vitro and in vivo.
  • ROME interacts with vimentin, increasing cancer cell intravasation.
  • Elevated ROME expression correlates with poor patient survival across multiple cancers.

Conclusions:

  • ROME is a biologically active plasma membrane glycoprotein critical for vertebrate development and metastasis.
  • ROME represents a novel therapeutic target for inhibiting cancer progression.