Pharmaceutical Sciences Faculty Publications

Sulfiredoxin-Peroxiredoxin IV Axis Promotes Human Lung Cancer Progression Through Modulation of Specific Phosphokinase Signaling

Document Type

Article

Publication Date

4-26-2011

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

ISSN

1091-6490

Volume

108

Issue

17

First Page

7004

Last Page

7009

DOI

10.1073/pnas.1013012108

PubMed ID

21487000

PubMed Central® ID

PMC3084097

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.

Keywords

Cell line, tumor, gene knockdown techniques, lung neoplasms, neoplasm invasiveness, oxidative stress, signal transduction

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