BackgroundY-box binding protein-1 is an evolutionary conserved transcription and translation regulating protein that is overexpressed in various human malignancies, including breast cancer. Despite reports of YB-1 and its association with distant spread of breast cancer, the intrinsic mechanism underlying this observation remains elusive. This study investigates the role of YB-1 in mediating metastasis in highly invasive breast cancer cell lines.MethodsSilencing the YBX1 gene (which encodes the YB-1 protein) by small interfering RNA (siRNA) was performed in MDA-MB-231 and Hs578T breast cancer cell lines, followed by phenotypic assays including cell migration and invasion assays. Gene expression profiling using Affymetrix GeneChip® Human Transcriptome 2.0 array was subsequently carried out in YB-1 silenced MDA-MB-231 cells. Overexpression and silencing of YBX1 were performed to assess the expression of CORO1C, one of the differentially regulated genes from the transcriptomic analysis. A Gaussia luciferase reporter assay was used to determine if CORO1C is a putative YB-1 downstream target. siRNA-mediated silencing of CORO1C and down-regulation of YBX1 in CORO1C overexpressing MDA-MB-231 cells were performed to evaluate cell migration and invasion.ResultsDownregulation of the YB-1 protein inhibited cell migration and invasion in MDA-MB-231 breast cancer cells. Global gene expression profiling in the YBX1 silenced MDA-MB-231 cells identified differential expression of several genes, including CORO1C (which encodes for an actin binding protein, coronin-1C) as a potential downstream target of YB-1. While knockdown of YBX1 gene decreased CORO1C gene expression, the opposite effects were seen in YB-1 overexpressing cells. Subsequent verification using the reporter assay revealed that CORO1C is an indirect downstream target of YB-1. Silencing of CORO1C by siRNA in MDA-MB-231 cells was also observed to reduce cell migration and invasion. Silencing of YBX1 caused a similar reduction in CORO1C expression, concomitant with a significant decrease in migration in Hs578T cells. In coronin-1C overexpressing MDA-MB-231 cells, increased migration and invasion were abrogated by YB-1 knockdown.ConclusionIt would appear that YB-1 could regulate cell invasion and migration via downregulation of its indirect target coronin-1C. The association between YB-1 and coronin-1C offers a novel approach by which metastasis of breast cancer cells could be targeted and abrogated.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3187-7) contains supplementary material, which is available to authorized users.

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Complement component 1, q subcomponent binding protein (C1QBP), is a multi-compartmental protein with higher mRNA expression reported in breast cancer tissues. This study evaluated the association between immunohistochemical expression of the C1QBP protein in breast cancer tissue microarrays (TMAs) and clinicopathological parameters, in particular tumor size. In addition, an in vitro study was conducted to substantiate the breast cancer TMA findings. Breast cancer TMAs were constructed from pathological specimens of patients diagnosed with invasive ductal carcinoma. C1QBP protein and proliferating cell nuclear antigen (PCNA) immunohistochemical analyses were subsequently performed in the TMAs. C1QBP immunostaining was detected in 131 out of 132 samples examined. The C1QBP protein was predominantly localized in the cytoplasm of the breast cancer cells. Univariate analysis revealed that a higher C1QBP protein expression was significantly associated with older patients (P = 0.001) and increased tumor size (P = 0.002). Multivariate analysis showed that C1QBP is an independent predictor of tumor size in progesterone-positive tumors. Furthermore, C1QBP was also significantly correlated with expression of PCNA, a known marker of proliferation. Inhibition of C1QBP expression was performed by transfecting C1QBP siRNA into T47D breast cancer cells, a progesterone receptor-positive breast cancer cell line. C1QBP gene expression was analyzed by real-time RT-PCR, and protein expression by Western blot. Cell proliferation assays were also performed by commercially available assays. Down-regulation of C1QBP expression significantly decreased cell proliferation and growth in T47D cells. Taken together, our findings suggest that the C1QBP protein could be a potential proliferative marker in breast cancer.

Serglycin is a multifunctional molecule and one of the first proteoglycans to be cloned. In this manuscript, we examine the physiological roles of serglycin in immunity, hemostasis, cell growth, apoptosis, and reproduction. In addition, we review recent studies on the involvement of serglycin in various pathological conditions, including cancer, inflammatory diseases, and platelet disorders. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.

The Y-Box protein- associated acidic protein (YBAP1), also known as Complement component 1, q subcomponent binding protein, is a multifunctional protein which is involved in in the regulation of complement activation, pre-mRNA splicing and mitochondrial function. As YBAP1 has been implicated in tumorigenesis, this study evaluates its role in breast cancer metastasis. YBAP1 mRNA expression was analysed by quantitative real time RT-PCR and YBAP1 protein by Western blot, immunocytochemical and immunofluorescence staining in a panel of breast cancer cell lines. Down-regulation of the YBAP1 gene in MDA-MB-231 breast cancer cells was performed by siRNA-mediated silencing and overexpression of the gene by transfection with the pCI-neo-YBAP1 plasmid, before analysis of the effects on cell migration and invasion. YBAP1 gene profiling was also performed in samples from the commercially available TissueScan Human Breast Cancer Panel 1 (Origene, Rockville, MD). YBAP1 immunohistochemical staining was carried out in breast cancer tissue microarrays constructed from 168 patients diagnosed with invasive ductal breast carcinoma. The YBAP1 immunostaining was performed using rabbit polyclonal anti-YBAP1 (RIKEN) at a dilution of 1:500. The percentage and intensity of YBAP1 immunopositive staining in malignant epithelial cells were recorded. YBAP1 was observed to be expressed in all the breast cancer cell lines (MCF-7, ZR-75, T47D and MDA-MB-231) examined. The protein was observed to be localized in the cytoplasm of breast cancer cells. Overexpression of YBAP1 increased cell migration and invasion in the highly malignant MDA-MB-231 breast cancer cells. Conversely silencing of the YBAP1 gene had the opposite effect, resulting in reduced cell migration and invasion. YBAP1 gene expression was also found to be up-regulated in the more advanced stages of breast cancer (grouped as Stage 0, I and IIa and compared with Stage II b, IIIa and IIIc; P <0.05). For the tissue microarrays, a positive correlation was observed between YBAP1 immunostaining and axillary lymph node status. YBAP1 augments the spread of breast cancer by enhancing cell migration and invasion. Hence, YBAP1 is a potential metastatic biomarker and targeting YBAP1 could be a strategy to combat breast cancer metastasis. Citation Format: Olivia J. Scully, Aye Aye Thike, George Wai-Cheong Yip, Puay Hoon Tan, Ken Matsumoto, Boon Huat Bay. Y-box protein-associated acidic protein promotes breast cancer progression and is a potential molecular target. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1992. doi:10.1158/1538-7445.AM2014-1992

The findings suggest that CLDN 12 expression could be clinically useful for predicting the survival of the ER-negative subgroup of patients with breast cancer.

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The preoperative diagnosis of intraosseous schwannoma is challenging because of its rarity. We report a resected case of sternal intraosseous schwannnoma mimicking late recurrence of breast cancer. A 60-year-old Japanese woman with a history of breast cancer was diagnosed as having a sternal tumor by chest computed tomography (CT) demonstrating a round, well-defined, low-density nodule measuring 3.3 × 2.8 cm, which was located almost at the center of the sternum and associated with bone lysis and erosion. [18 F]Fluorodeoxyglucose positron emission tomography (FDG-PET)/CT demonstrated FDG accumulation in the tumor, suggesting malignancy. Therefore, late isolated recurrence of breast cancer was suspected. Surgical resection was performed for both confirmation of the diagnosis and treatment. Pathological examination revealed that the tumor was composed predominantly of spindle-shaped cells arranged in a typical palisading pattern, being compatible with schwannoma. Although the periosteum was intact, the tumor was found to have destroyed the cortex of the sternum and proceeded forward to the bone marrow. Additionally, immunohistochemical staining revealed that the lesion was diffusely and strongly positive for S-100 protein. Thus metastasis from breast cancer was ruled out on the basis of the features revealed by microscopy.