SOD1 regulates ribosome biogenesis in KRAS mutant non-small cell lung cancer

Xiaowen Wang1,2,3, Hong Zhang1,2, Russell Sapio4

  • 1Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.

Nature Communications
|April 16, 2021
PubMed

Insights

Nuclear superoxide dismutase 1 (SOD1) is crucial for KRAS-driven lung cancer cell growth by regulating ribosome biogenesis. Knocking out SOD1 significantly reduces tumor burden and blocks cancer cell proliferation.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Superoxide dismutase 1 (SOD1) is a key antioxidant enzyme.
  • Its precise role in cancer, particularly non-small cell lung cancer (NSCLC), remains incompletely understood.
  • SOD1 is a potential anticancer target.

Purpose of the Study:

  • To investigate the function of SOD1 in KRAS-driven NSCLC.
  • To elucidate the specific mechanisms by which SOD1 influences lung cancer cell proliferation.

Main Methods:

  • Generation of an inducible Sod1 knockout in a KRAS-driven NSCLC mouse model.
  • In vitro and in vivo assessment of tumor burden and cell growth.
  • Subcellular localization studies of SOD1.
  • Analysis of SOD1 interaction with the PeBoW complex and its role in ribosome biogenesis.

Main Results:

  • Sod1 knockout significantly reduced tumor burden in vivo and inhibited KRAS mutant NSCLC cell growth in vitro.
  • SOD1 was found to be enriched in the nucleus and nucleolus of NSCLC cells.
  • Nuclear/nucleolar SOD1, not cytoplasmic, was essential for lung cancer cell proliferation.
  • SOD1 interacts with the PeBoW complex, controlling its assembly and pre-60S ribosomal subunit maturation.
  • SOD1 regulates pre-ribosomal RNA processing and cytoplasmic 60S ribosomal subunit maturation.

Conclusions:

  • Nuclear SOD1 plays a critical role in ribosome biogenesis and proliferation in KRAS-driven NSCLC.
  • This study reveals a novel nuclear function of SOD1 essential for lung cancer cell survival.

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