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RNAi screens in mice identify physiological regulators of oncogenic growth

Slobodan Beronja1, Peter Janki, Evan Heller

  • 1Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology & Development, The Rockefeller University, New York, New York 10065, USA.

Nature
|August 16, 2013
PubMed

Insights

This study used genome-wide RNA interference screens in mice to identify regulators of skin development and cancer. Researchers discovered new genes, including Mllt6 and β-catenin, that control tissue growth and hyperproliferation.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cancer Research

Background:

  • Tissue growth is complex, involving cell capabilities and environmental interactions.
  • Understanding tissue growth is crucial for human development and cancer research.
  • Previous research lacked comprehensive in vivo genome-wide screens for tissue growth regulators.

Purpose of the Study:

  • To perform the first genome-wide RNA-interference-mediated screens in mice.
  • To identify regulators of embryonic epidermal growth and oncogenic hyperplasia.
  • To validate the role of identified regulators in mouse and human cancers.

Main Methods:

  • Conducted genome-wide RNA-interference screens in mice.
  • Focused on skin development and Hras(G12V)-induced oncogenic hyperplasia.
  • Validated findings in mouse and human cancer models.

Main Results:

  • Identified novel and known regulators of embryonic epidermal growth.
  • Mllt6 and β-catenin were top hits, maintaining Hras(G12V)-dependent hyperproliferation.
  • β-catenin antagonizes normal epidermal growth via Wnt-independent adhesion.

Conclusions:

  • In vivo mammalian genome-wide investigations are feasible for dissecting tissue development and tumorigenesis.
  • Identified oncogenic growth regulators provide potential targets for cancer therapies.
  • This work establishes a framework for future studies on tissue growth and cancer.

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