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Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ
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Sulfiredoxin is an AP-1 target gene that is required for transformation and shows elevated expression in human skin

Qiou Wei1, Hong Jiang, Connie P Matthews

  • 1Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 6, 2008
PubMed

Insights

Sulfiredoxin (Srx) is a novel target of activator protein-1 (AP-1) that plays a critical role in skin cancer. Inhibiting Srx may offer a new strategy for cancer prevention and treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Dominant-negative c-Jun (TAM67) inhibits skin carcinogenesis.
  • Activator protein-1 (AP-1) is a key transcription factor in carcinogenesis.

Purpose of the Study:

  • Identify novel targets of AP-1 activation and TAM67 inhibition.
  • Investigate the role of Sulfiredoxin (Srx) in skin carcinogenesis and redox homeostasis.

Main Methods:

  • Utilized short hairpin RNA (shRNA) and overexpression to manipulate Srx levels.
  • Assessed Srx function in JB6 cells regarding transformation and oxidative stress sensitivity.
  • Examined c-Jun phosphorylation and AP-1 activity.
  • Screened patient skin cancer tissues using tissue microarrays.

Main Results:

  • Identified Sulfiredoxin (Srx) as a unique target of AP-1 and TAM67.
  • Demonstrated Srx's critical role in maintaining redox homeostasis by reducing hyperoxidized peroxiredoxins.
  • Showed that Srx knockdown abolishes tumor promoter-induced transformation and increases oxidative stress sensitivity in JB6 cells.
  • Found that Srx knockdown impairs c-Jun phosphorylation, suggesting a feedback role in AP-1 regulation.
  • Observed elevated Srx expression in human skin cancers.

Conclusions:

  • Srx is a significant target of AP-1 blockade.
  • Srx plays a crucial role in redox balance and cellular transformation.
  • Targeting Srx presents a potential therapeutic strategy for skin cancer prevention and treatment.

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