BlyS is up-regulated by hypoxia and promotes migration of human breast cancer cells

Abstract

BackgroundThe role of B Lymphocyte Stimulator (BLyS) in the survival of malignant B cells and the maintenance of normal B cell development and homeostasis has been intensively studied in the literature. However, the influence of BLyS on breast cancer progression remains unclear. The study aimed to investigate the effect of hypoxia on BLyS regulation, cell migratory response to BLyS and the possible molecular mechanisms.MethodsIn this study, we examined the role of BLyS in the migration of human breast cancer cells by transwell assay. We also explored whether BLyS and its receptors expressed in human breast cancer cell lines by immunofluorescence and Western Blotting. Then we detected the expression level of BLyS in both normoxic and hypoxic conditions by real time-PCR and Western Blotting. Pathways involved were confirmed by Western Blotting, immunofluorescence, transwell assay and luciferase assay.ResultsAccording to our study, the expression level of BlyS was increased in human breast cancer cell lines in hypoxic conditions. Up-regulation of this protein led to activation and nuclear translocation of NF-kappa B p65. We also found that the number of migrated cells was increased in the presence of BLyS and inhibition of phosphorylation of Akt attenuated the enhanced migratory response.ConclusionsIt suggested that better understanding of BLyS, an immunopotentiator, may offer a potential therapeutic target for the treatment of human breast cancers. In addition, BLyS promoted breast cancer cells migration, underscoring the necessity of appropriate applications of immunopotentiators to cancer treatment.

Gankyrin is essential for hypoxia enhanced metastatic potential in breast cancer cells

“…A previous study showed that HIF-1α and HIF-2α accumulated in breast cancer cells with hypoxia and potentiated Notch signaling (20). The hypoxic conditions increased the expression of BlyS in human breast cancer cell lines, and upregulation of BlyS led to activation and nuclear translocation of NF-κB p65, which also increased the migration and invasion of breast cancer cells (21). A recent study showed that gankyrin binds to and sequesters factors inhibiting FIH-1, resulting in a decreased interaction between FIH-1 and HIF-1α, which increased activity of HIF-1 to promote VEGF production (16), indicating that gankyrin is significant in the hypoxia-associated phenotype in breast cancer cells.…”

Epithelial-Mesenchymal Transition and Breast Cancer

“…The stem-like characteristics of the cells which had undergone an EMT were confirmed by in vitro spheres assay and in vivo mouse model. Clinical studies have shown that the CD44 high /CD24 low phenotype was more prevalent in triple negative (ER/PR- and HER2-) breast cancer (TNBC) and is associated with increased risk for metastases to distant organs compared to other types of breast cancer [ 37 , 38 , 39 , 40 , 41 ].…”

Frequency and prognostic significant of CYP3A4-A-290G polymorphism in acute myeloid leukemia

“…Recent evidence indicates that enzymes involved in carcinogen activation or deactivation as well as their encoding genes, might play critical roles in determining individual susceptibility to cancers. Polymorphisms in these genes encoding the enzymes, possibly by altering their functions, could affect carcinogen activation (either increase or decrease) and modulating DNA repair processes [3] . Cytochrome P450 enzymes are essential role in the phase I dependent metabolism of drugs and all other xenobiotics [4] .…”