QSOX sulfhydryl oxidase in rat adenohypophysis: localization and regulation by estrogens

Tury, Anna; Mairet-Coello, Georges; Poncet, Fabrice; Jacquemard, Claude; Risold, Pierre‐Yves; Fellmann, D; Griffond, Beŕnadette

doi:10.1677/joe.1.05842

Cited by 28 publications

(25 citation statements)

References 44 publications

(55 reference statements)

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“…The primary enzymatic function of QSOX1 is oxidation of sulfhydryl groups, generating disulfide bonds in proteins, ultimately reducing oxygen to hydrogen peroxide [6-8]. Previous work has reported the localization of QSOX1 to the Golgi apparatus and endoplasmic reticulum in human embryonic fibroblasts where it works independently as well as with protein disulfide isomerase to help fold nascent proteins in the cell [9-11]. …”

Section: Introductionmentioning

confidence: 99%

Expression of quiescin sulfhydryl oxidase 1 is associated with a highly invasive phenotype and correlates with a poor prognosis in Luminal B breast cancer

et al. 2013

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IntroductionQuiescin sulfhydryl oxidase 1 (QSOX1) oxidizes sulfhydryl groups to form disulfide bonds in proteins. Tumor specific expression of QSOX1 has been reported for numerous tumor types. In this study, we investigate QSOX1 as a marker of breast tumor progression and evaluate the role of QSOX1 as it relates to breast tumor growth and metastasis.MethodsCorrelation of QSOX1 expression with breast tumor grade, subtype and estrogen receptor (ER) status was gathered through informatic analysis using the "Gene expression based Outcome for Breast cancer Online" (GOBO) web-based tool. Expression of QSOX1 protein in breast tumors tissue microarray (TMA) and in a panel of breast cancer cell lines was used to confirm our informatics analysis. To investigate malignant cell mechanisms for which QSOX1 might play a key role, we suppressed QSOX1 protein expression using short hairpin (sh) RNA in ER+ Luminal A-like MCF7, ER+ Luminal B-like BT474 and ER- Basal-like BT549 breast cancer cell lines.ResultsGOBO analysis revealed high levels of QSOX1 RNA expression in ER+ subtypes of breast cancer. In addition, Kaplan Meyer analyses revealed QSOX1 RNA as a highly significant predictive marker for both relapse and poor overall survival in Luminal B tumors. We confirmed this finding by evaluation of QSOX1 protein expression in breast tumors and in a panel of breast cancer cell lines. Expression of QSOX1 in breast tumors correlates with increasing tumor grade and high Ki-67 expression. Suppression of QSOX1 protein slowed cell proliferation as well as dramatic inhibition of MCF7, BT474 and BT549 breast tumor cells from invading through Matrigel™ in a modified Boyden chamber assay. Inhibition of invasion could be rescued by the exogenous addition of recombinant QSOX1. Gelatin zymography indicated that QSOX1 plays an important role in the function of MMP-9, a key mediator of breast cancer invasive behavior.ConclusionsTaken together, our results suggest that QSOX1 is a novel biomarker for risk of relapse and poor survival in Luminal B breast cancer, and has a pro-proliferative and pro-invasive role in malignant progression partly mediated through a decrease in MMP-9 functional activity.

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Section: Introductionmentioning

confidence: 99%

Expression of quiescin sulfhydryl oxidase 1 is associated with a highly invasive phenotype and correlates with a poor prognosis in Luminal B breast cancer

et al. 2013

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“…QSOX1 is located on chromosome 1q24 and is an ancient gene fusion from thioredoxin (TRX) and ERV1, a yeast sulfhydryl oxidase (20). Bioinformatic searches revealed a signal sequencesuggesting secretion, but no KDEL endoplasmic reticulumretention sequence, despite subsequent findings of QSOX1 localization in the ER and, more recently, in the Golgi (44,82,85). QSOX1 homology domains with sequence similarity to protein disulfide isomerase (PDI) were identified at the N-terminus of the protein followed by one functional and one nonfunctional TRX domain.…”

Section: Brief History Of Qsox1mentioning

confidence: 99%

The Emerging Role of QSOX1 in Cancer

Lake

Faigel

2014

Antioxidants & Redox Signaling

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Significance: Quiescin sulfhydryl oxidase 1 (QSOX1) is an enzyme that oxidizes thiols during protein folding, reducing molecular oxygen to hydrogen peroxide. Tumor cells may take advantage of oxidative environments at different stages of tumorigenesis, but QSOX1 may also serve additional functions in tumors. Recent Advances: Several groups have reported the over-expression of QSOX1 in breast, pancreas, and prostate cancers. A consensus is building that QSOX1 over-expression is important during tumor cell invasion, facilitating tumor cell migration at the tumor-stroma interface. As such, QSOX1 may be considered a prognostic indicator of metastatic potential or even indicate that cancer is present in a host. Critical Issues: However, some controversy exists between QSOX1 as a marker of poor or favorable outcome in breast cancer. More studies are required to reveal what advantage QSOX1 provides to breast and other types of cancer. More specifically, it is critical to learn which tumor types over-express QSOX1 and use its enzymatic activity to their advantage. Future Directions: As interest increases in understanding the mechanisms of tumorigenesis within the extracellular matrix and how tumor cells influence fibroblasts and other stromal cells, QSOX1 may be revealed as an important player in cancer detection and prognosis. Defining the mechanism(s) of QSOX1 activity in tumors and in in vivo models will provide important insights into how to target QSOX1 with anti-neoplastic agents. Antioxid. Redox Signal. 21, 485-496.

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“…Moreover, no signal for permanent retention in the endoplasmic reticulum (KDEL sequence) was identified, suggesting an extracellular destination [4]. In addition, QSOX1 proteins have been detected in the endoplasmic reticulum, the Golgi apparatus and the secretion vesicles [5]. These proteins can also be found in culture supernatant and in extracellular spaces, confirming that they are secreted [1].…”

Section: Introductionmentioning

confidence: 99%

High expression of QSOX1 reduces tumorogenesis, and is associated with a better outcome for breast cancer patients

et al. 2012

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IntroductionThe gene quiescin/sulfhydryl oxidase 1, QSOX1, encodes an enzyme directed to the secretory pathway and excreted into the extracellular space. QSOX1 participates in the folding and stability of proteins and thus could regulate the biological activity of its substrates in the secretory pathway and/or outside the cell. The involvement of QSOX1 in oncogenesis has been studied primarily in terms of its differential expression in systemic studies. QSOX1 is overexpressed in prostate cancers and in pancreatic adenocarcinoma. In contrast, QSOX1 gene expression is repressed in endothelial tumors. In the present study, we investigated the role of QSOX1 in breast cancer.MethodsWe analyzed QSOX1 mRNA expression in a cohort of 217 invasive ductal carcinomas of the breast. Moreover, we investigated QSOX1's potential role in regulating tumor growth and metastasis using cellular models in which we overexpressed or extinguished QSOX1 and xenograft experiments.ResultsWe showed that the QSOX1 expression level is inversely correlated to the aggressiveness of breast tumors. Our results show that QSOX1 leads to a decrease in cell proliferation, clonogenic capacities and promotes adhesion to the extracellular matrix. QSOX1 also reduces the invasive potential of cells by reducing cell migration and decreases the activity of the matrix metalloproteinase, MMP-2, involved in these mechanisms. Moreover, in vivo experiments show that QSOX1 drastically reduces the tumor development.ConclusionsTogether, these results suggest that QSOX1 could be posited as a new biomarker of good prognosis in breast cancer and demonstrate that QSOX1 inhibits human breast cancer tumorogenesis.

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QSOX sulfhydryl oxidase in rat adenohypophysis: localization and regulation by estrogens

Cited by 28 publications

References 44 publications

Expression of quiescin sulfhydryl oxidase 1 is associated with a highly invasive phenotype and correlates with a poor prognosis in Luminal B breast cancer

Expression of quiescin sulfhydryl oxidase 1 is associated with a highly invasive phenotype and correlates with a poor prognosis in Luminal B breast cancer

The Emerging Role of QSOX1 in Cancer

High expression of QSOX1 reduces tumorogenesis, and is associated with a better outcome for breast cancer patients

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