The Sulfiredoxin-peroxiredoxin (Srx-Prx) Axis in Cell Signal Transduction and Cancer Development

Overview

Journal Cancer Lett

Specialty Oncology

Date 2015 Jul 15

PMID 26170166

Citations 43

Authors

Murli Mishra

Hong Jiang

Lisha Wu

Hedy A Chawsheen

Qiou Wei

Affiliations

Soon will be listed here.

Abstract

Redox signaling is a critical component of cell signaling pathways that are involved in the regulation of cell growth, metabolism, hormone signaling, immune regulation and variety of other physiological functions. Peroxiredoxin (Prx) is a family of thiol-based peroxidase that acts as a regulator of redox signaling. Members of Prx family can act as antioxidants and chaperones. Sulfiredoxin (Srx) is an antioxidant protein that exclusively reduces over-oxidized typical 2-Cys Prx. Srx has different affinities for individual Prx and it also catalyzes the deglutathionylation of variety of substrates. Individual component of the Srx-Prx system plays critical role in carcinogenesis by modulating cell signaling pathways involved in cell proliferation, migration and metastasis. Expression levels of individual component of the Srx-Prx axis have been correlated with patient survival outcome in multiple cancer types. This review will summarize the molecular basis of differences in the affinity of Srx for individual Prx and the role of individual component of the Srx-Prx system in tumor progression and metastasis. This enhanced understanding of molecular aspects of Srx-Prx interaction and its role in cell signal transduction will help define the Srx-Prx system as a future therapeutic target in human cancer.

Citing Articles

Neuronal Injury after Ischemic Stroke: Mechanisms of Crosstalk Involving Necroptosis.

Zhang X, Li H, Zhao Y, Zhao T, Wang Z, Tang Q J Mol Neurosci. 2025; 75(1):15.

PMID: 39903429 DOI: 10.1007/s12031-025-02313-y.

CRL3 E3 ligase facilitates ubiquitin-mediated degradation of oncogenic SRX to suppress colorectal cancer progression.

Zhu F, Li L, Chen Y, Pan Y, Zhang W, Li L Nat Commun. 2024; 15(1):10536.

PMID: 39627198 PMC: 11615322. DOI: 10.1038/s41467-024-54919-2.

Glutathione-Dependent Pathways in Cancer Cells.

Kalinina E Int J Mol Sci. 2024; 25(15).

PMID: 39125992 PMC: 11312684. DOI: 10.3390/ijms25158423.

Protein Oxidative Modifications in Neurodegenerative Diseases: From Advances in Detection and Modelling to Their Use as Disease Biomarkers.

Anjo S, He Z, Hussain Z, Farooq A, McIntyre A, Laughton C Antioxidants (Basel). 2024; 13(6).

PMID: 38929122 PMC: 11200609. DOI: 10.3390/antiox13060681.

Mitochondrial Physiology of Cellular Redox Regulations.

Jezek P, Dlaskova A, Engstova H, Spackova J, Tauber J, Pruchova P Physiol Res. 2024; 73(S1):S217-S242.

PMID: 38647168 PMC: 11412358. DOI: 10.33549/physiolres.935269.

References

Dietz K . Plant peroxiredoxins. Annu Rev Plant Biol. 2003; 54:93-107. DOI: 10.1146/annurev.arplant.54.031902.134934. View

Lee T, Kim S, Yu S, Kim S, Park D, Moon H . Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice. Blood. 2003; 101(12):5033-8. DOI: 10.1182/blood-2002-08-2548. View

Chen L, Na R, Gu M, Salmon A, Liu Y, Liang H . Reduction of mitochondrial H2O2 by overexpressing peroxiredoxin 3 improves glucose tolerance in mice. Aging Cell. 2008; 7(6):866-78. PMC: 4431549. DOI: 10.1111/j.1474-9726.2008.00432.x. View

Wei Q, Jiang H, Baker A, Dodge L, Gerard M, Young M . Loss of sulfiredoxin renders mice resistant to azoxymethane/dextran sulfate sodium-induced colon carcinogenesis. Carcinogenesis. 2013; 34(6):1403-10. PMC: 3670259. DOI: 10.1093/carcin/bgt059. View

Roumes H, Pires-Alves A, Gonthier-Maurin L, Dargelos E, Cottin P . Investigation of peroxiredoxin IV as a calpain-regulated pathway in cancer. Anticancer Res. 2010; 30(12):5085-9. View

Wonsey D, Zeller K, Dang C . The c-Myc target gene PRDX3 is required for mitochondrial homeostasis and neoplastic transformation. Proc Natl Acad Sci U S A. 2002; 99(10):6649-54. PMC: 124457. DOI: 10.1073/pnas.102523299. View

Hanschmann E, Godoy J, Berndt C, Hudemann C, Lillig C . Thioredoxins, glutaredoxins, and peroxiredoxins--molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling. Antioxid Redox Signal. 2013; 19(13):1539-605. PMC: 3797455. DOI: 10.1089/ars.2012.4599. View

Kim Y, Ahn J, Liang P, Ip C, Zhang Y, Park Y . Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation: implication to tumor biology. Cancer Res. 2007; 67(2):546-54. DOI: 10.1158/0008-5472.CAN-06-2401. View

Li K, Pang J, Lau K, Zhou L, Mao Y, Wang Y . MiR-383 is downregulated in medulloblastoma and targets peroxiredoxin 3 (PRDX3). Brain Pathol. 2012; 23(4):413-25. PMC: 8029115. DOI: 10.1111/bpa.12014. View

10.

Hu J, Gao Q, Li L . Peroxiredoxin 3 is a novel marker for cell proliferation in cervical cancer. Biomed Rep. 2014; 1(2):228-230. PMC: 3956212. DOI: 10.3892/br.2012.43. View

11.

Molin M, Yang J, Hanzen S, Toledano M, Labarre J, Nystrom T . Life span extension and H(2)O(2) resistance elicited by caloric restriction require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae. Mol Cell. 2011; 43(5):823-33. DOI: 10.1016/j.molcel.2011.07.027. View

12.

Yi N, Xiao M, Ni W, Jiang F, Lu C, Ni R . High expression of peroxiredoxin 4 affects the survival time of colorectal cancer patients, but is not an independent unfavorable prognostic factor. Mol Clin Oncol. 2014; 2(5):767-772. PMC: 4106752. DOI: 10.3892/mco.2014.317. View

13.

Randall L, Manta B, Hugo M, Gil M, Batthyany C, Trujillo M . Nitration transforms a sensitive peroxiredoxin 2 into a more active and robust peroxidase. J Biol Chem. 2014; 289(22):15536-43. PMC: 4140909. DOI: 10.1074/jbc.M113.539213. View

14.

Cho C, Yoon H, Kim J, Woo H, Rhee S . Circadian rhythm of hyperoxidized peroxiredoxin II is determined by hemoglobin autoxidation and the 20S proteasome in red blood cells. Proc Natl Acad Sci U S A. 2014; 111(33):12043-8. PMC: 4142998. DOI: 10.1073/pnas.1401100111. View

15.

McKean D, Sisbarro L, Ilic D, Kaplan-Alburquerque N, Nemenoff R, Weiser-Evans M . FAK induces expression of Prx1 to promote tenascin-C-dependent fibroblast migration. J Cell Biol. 2003; 161(2):393-402. PMC: 2172901. DOI: 10.1083/jcb.jcb.200302126. View

16.

Hoshino I, Matsubara H, Hanari N, Mori M, Nishimori T, Yoneyama Y . Histone deacetylase inhibitor FK228 activates tumor suppressor Prdx1 with apoptosis induction in esophageal cancer cells. Clin Cancer Res. 2005; 11(21):7945-52. DOI: 10.1158/1078-0432.CCR-05-0840. View

17.

Merikallio H, Paakko P, Kinnula V, Harju T, Soini Y . Nuclear factor erythroid-derived 2-like 2 (Nrf2) and DJ1 are prognostic factors in lung cancer. Hum Pathol. 2011; 43(4):577-84. DOI: 10.1016/j.humpath.2011.05.024. View

18.

Riddell J, Maier P, Sass S, Moser M, Foster B, Gollnick S . Peroxiredoxin 1 stimulates endothelial cell expression of VEGF via TLR4 dependent activation of HIF-1α. PLoS One. 2012; 7(11):e50394. PMC: 3503895. DOI: 10.1371/journal.pone.0050394. View

19.

Ummanni R, Barreto F, Venz S, Scharf C, Barett C, Mannsperger H . Peroxiredoxins 3 and 4 are overexpressed in prostate cancer tissue and affect the proliferation of prostate cancer cells in vitro. J Proteome Res. 2012; 11(4):2452-66. DOI: 10.1021/pr201172n. View

20.

Biteau B, Labarre J, Toledano M . ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin. Nature. 2003; 425(6961):980-4. DOI: 10.1038/nature02075. View