title: Sulfiredoxin-Peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling.
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.
authors.affiliation: Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. weiqiou@mail.nih.gov
authors.forename: Qiou
authors.initials: Q
authors.lastname: Wei
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xiao
authors.forename: Alyson
authors.initials: A
authors.lastname: Baker
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Young
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Colburn
mesh_terms: D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D018808:Transcription Factor AP-1; C515980:PRDX4 protein, human; D054464:Peroxiredoxins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C504024:SRXN1 protein, human; D010770:Phosphotransferases