Abstract
BackgroundSyndecan binding protein (SDCBP), an adapter protein containing PDZ domains, contributes to the tumorigenicity and metastasis of many malignant tumors, such as malignant melanoma. Our study aimed in revealing the expression profile of SDCBP in breast cancer (BCa) and its role in tumor cell proliferation, and then exploring its value in the targeted treatment of BCa.Methodology/Principal FindingsWe first evaluated the SDCBP expression by immunohistochemistry in normal breast and BCa tissues. Then we explored the expression profile of SDCBP in different BCa cell lines. By constructing SDCBP-silenced BCa cell clones, we further assessed the effects of SDCBP suppression on tumor cells in vitro by cell culture and in vivo by tumorigenicity. SDCBP expression was detected in 80.6% (n = 160) of BCa tissues, in contrast to its expression in 13% (n = 23) of normal breast tissues (P<0.001). Among the tumors, the level of its expression was positively correlated with histological grade and tumor staging while negatively correlated with the estrogen receptor (ER) expression. Higher expression of SDCBP was also noted in ER-negative BCa cell lines. It was also identified that SDCBP expression was down-regulated in a dose-dependent mode by 17-β estradiol in estrogen-responsive MCF-7. Furthermore, SDCBP silence inhibited ER-negative tumor cell growth in vivo and in vitro. Cell cycle studies showed that SDCBP silence increased G1 cell population and resulted in related cell-cycle-regulator changes: up-regulation of p21 and p27 while down-regulation of cyclin E.Conclusion/SignificanceOur results suggested that SDCBP played an important role in tumor growth of ER-negative BCas. In these tumors where the estrogen signaling pathway is not available, SDCBP probably contribute to tumor growth through an alternative signaling pathway by promoting tumor cells passing the G1/S checkpoint into the cell cycle. Suppression of SDCBP expression may have its potential to become a targeted therapy for ER-negative BCas.
Highlights
Breast cancer (BCa) is a heterogeneous disease including multiple subgroups with different molecular signatures, clinical characteristics, and responses to therapies [1]
The estrogen receptor (ER) negative BCa, particular the triple negative breast cancer (TNBC) which refers to any BCa that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) or Human Epidermal Growth Factor Receptor 2 (HER-2/neu), has more aggressive clinical course and less effective treatments due to lack of specific targets
SCDBP is investigated as a candidate marker that may participate in the alternative pathways to maintain the growth of BCa cells without functional ER
Summary
Breast cancer (BCa) is a heterogeneous disease including multiple subgroups with different molecular signatures, clinical characteristics, and responses to therapies [1]. Syndecan binding protein (SDCBP), known as ‘‘syntenin’’ and melanoma differentiation associated gene-9 (MDA-9), was initially identified as a molecule linking syndecan-mediated signaling to the cytoskeleton [3]. It is a PDZ-domain-containing molecule that has many interaction partners, and regulates transmembrane-receptor trafficking, tumor-cell metastasis and neuronal-synapse function [4]. Li et al found, when eukaryotic translation initiation factor 5A (eIF5A) interacted with SDCBP, the eIF5A-induced increase in p53 protein level was significantly inhibited. This study is undertaken to evaluate the expression profile of SDCBP in BCa and to explore its role in the tumor cell proliferation, and to assess its potential value in the targeted treatment of BCa
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