Tumor promoter-induced sulfiredoxin is required for mouse skin tumorigenesis

Lisha Wu, Hong Jiang, Hedy A. Chawsheen, Murli Mishra, Matthew R. Young, Matthieu Gerard, Michel B. Toledano, Nancy H. Colburn, Qiou Wei

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Sulfiredoxin (Srx), the exclusive enzyme that reduces the hyperoxidized inactive form of peroxiredoxins (Prxs), has been found highly expressed in several types of human skin cancer. To determine whether Srx contributed to skin tumorigenesis in vivo, Srx null mice were generated on an FVB background. Mouse skin tumorigenesis was induced by a 7,12-dimethylbenz[α]anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) protocol. We found that the number, volume and size of papillomas in Srx-/- mice were significantly fewer compared with either wild-type (Wt) or heterozygous (Het) siblings. Histopathological analysis revealed more apoptotic cells in tumors from Srx-/- mice. Mechanistic studies in cell culture revealed that Srx was stimulated by TPA in a redox-independent manner. This effect was mediated transcriptionally through the activation of mitogen-activated protein kinase and Jun-N-terminal kinase. We also demonstrated that Srx was capable of reducing hyperoxidized Prxs to facilitate cell survival under oxidative stress conditions. These findings suggested that loss of Srx protected mice, at least partially, from DMBA/TPA-induced skin tumorigenesis. Therefore, Srx has an oncogenic role in skin tumorigenesis and targeting Srx may provide novel strategies for skin cancer prevention or treatment.

Original languageEnglish
Pages (from-to)1177-1184
Number of pages8
JournalCarcinogenesis
Volume35
Issue number5
DOIs
StatePublished - Apr 2014

ASJC Scopus subject areas

  • Cancer Research

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