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Quiescin 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.    Methods  Correlation 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.    Results  GOBO 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.    Conclusions  Taken 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.

breast cancer research

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