Zhu et al. Journal of Experimental & Clinical Cancer Research 2012, 31:31 http://www.jeccr.com/content/31/1/31 R E S E A R C H Open Access BlyS is up-regulated by hypoxia and promotes migration of human breast cancer cells Jing Zhu1†, Li Sun2†, Sensen Lin1, Renping Zhao2, Liqiang Zhou1, Dongdong Fang1, Liang Chen2, Jin Liu2, Wenting Shi2, Luyong Zhang2 and Shengtao Yuan1* Abstract Background: The 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. Methods: In 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. Results: According 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. Conclusions: It 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. Keywords: Hypoxia, BLyS, Cell migration Background B Lymphocyte Stimulator (BLyS), a key member of the tumor necrosis factor superfamily, binds to three recep- tors: B-cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI), and B cell-acti- vating factor receptor (BAFF-R). BLyS promotes survival of splenic immature transitional and mature B cells [1]. Over-expression of BLyS has been associated with mul- tiple myeloma (MM) [2], Systemic lupus erythematosus (SLE) [3] and B cell lymphoma [4]. It has also been reported that this ligand/receptor dyad plays a critical role in the growth and survival of malignant plasma * Correspondence: yuanst2@yahoo.com.cn † Contributed equally 1National Nanjing New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, Peoples Republic of China Full list of author information is available at the end of the article cells and B cells [5]. Recent studies in ductal breast can- cer patients have suggested a role of BLyS in the devel- opment of breast cancer. But its molecular mechanisms remain to be elucidated [6]. Hypoxia plays a significant role in the pathogenesis of heart disease, cancer, neuron death, etc. [7]. Inflamma- tory factors have been shown to be transcriptional regu- lated by hypoxia induced factor-1a (HIF-1a) or NF- kappa B in hypoxic conditions [8]. The expression of BLyS is up-regulated by hypoxia, while the mechanism is still uncertain. We hypothesized that HIF-1a or NF- kappa B pathway might be responsible for the up-regu- lation. In addition, the inflammatory factors such as TNF-a, IL-1a lead to increased cancer cell migration [9]. Therefore, the human breast cancer cell migration in response to BLyS and possible molecular mechanisms were explored in this study. © 2012 Zhu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.