Sulfiredoxin-peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling

Qiou Wei, Hong Jiang, Zhen Xiao, Alyson Baker, Matthew R. Young, Timothy D. Veenstra, Nancy H. Colburn

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Oxidative stress is known to cause tumorigenesis through induction of DNA and lipid damage. It also promotes cancer progression through a largely unknown mechanism. Sulfiredoxin (Srx) is a novel oxidative stress-induced antioxidant protein whose function in tumorigenesis and cancer progression has not been well studied. We report that Srx is highly expressed in human lung cancer. Knockdown of Srx reduces anchorage-independent colony formation, cell migration, and invasion of human lung cancer cells. Srx preferentially interacts with Peroxiredoxin (Prx) IV relative to other Prxs due to its intrinsic higher binding affinity. Knockdown of Prx IV recapitulates the phenotypic changes of depleting Srx. Disruption or enhancement of the Srx-Prx IV axis leads respectively to reduction or acceleration of tumor growth and metastasis formation in vivo. Through identification and validation of the downstream mediators we unraveled the Srx-mediated signaling network that traverses AP-1-activating and other phosphokinase signaling cascades. Our work reveals that the Srx-Prx IV axis is critical for lung cancer maintenance and metastasis, suggesting that targeting the Srx-Prx IV axis may provide unique effective strategies for cancer prevention and treatment.

Original languageEnglish
Pages (from-to)7004-7009
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number17
DOIs
StatePublished - Apr 26 2011

Funding

FundersFunder number
National Childhood Cancer Registry – National Cancer InstituteZIABC010025

    Keywords

    • Oncogene
    • Signal transduction

    ASJC Scopus subject areas

    • General

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