bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1978: The tyrosine kinase Syk plays a role in the maintenance of intercellular adhesive junctions in human breast cancer cells
Authors: Kassouf Toufic , Montcourrier Philippe , Larive Romain , Bettache Nadir , Morel Anne , Merezegue Fabrice , Urbach Serge , Coopman Peter J. 
Published: May 2015

Abstract
The non-receptor spleen tyrosine kinase Syk has mainly been studied in hematopoietic cells in which it plays a key role in the immune-response signalling. We previously demonstrated that Syk is also present in mammary epithelial cells and that its expression is lost during malignant progression of breast cancer cell lines. Clinical studies confirmed loss of Syk expression, not only in breast tumors but also in other carcinomas and melanoma. Xenotransplantation animal experiments evidenced that Syk acts as a tumor and metastasis suppressor in breast cancer and melanoma. The mechanisms by which Syk exerts its anti-oncogenic activity remain, however, unrevealed. Using a quantitative phospho-proteomic SILAC approach in breast cancer cells, we identified new potential Syk substrates involved in intercellular adhesion and epithelial cell polarity, both characters of cell differentiation that are lost during tumor progression.
Using in vitro kinase assays, we demonstrated that E-cadherin and various catenins are direct Syk substrates. The tyrosine residues phosphorylated by Syk were identified by mass spectrometry and phospho-peptide-specific antibodies were generated. By immunofluorescence, we observed that endogenous Syk and E-cadherin colocalize at adherens junctions and that transient DsRed-Syk transfection induces phospho-E-cadherin- and phospho-catenin epitopes at cell-cell contacts. Immunoprecipitation experiments indicate that phosphorylated E-cadherin and catenins are associated in a complex. Syk-mediated phosphorylation of E-cadherin seems to be important for the proper localization of p120-catenin at adherens junctions. Syk knockdown in breast cancer cells partially inhibits the re-aggregation of cells and increases invasion in Matrigel. Using Syk knockdown and overexpression we explored its potential role in the maintenance of an epithelial phenotype, preventing EMT.
In conclusion, Syk might play a role in the establishment and maintenance of intercellular junctions via the phosphorylation of the E-cadherin/catenin complex. Loss of Syk expression or function might lead to the destabilization of these complexes and promote invasion (supported by Fondation ARC SL220110603480)
Citation Format: Toufic Kassouf, Philippe Montcourrier, Romain Larive, Nadir Bettache, Anne Morel, Fabrice Merezegue, Serge Urbach, Peter J. Coopman. The tyrosine kinase Syk plays a role in the maintenance of intercellular adhesive junctions in human breast cancer cells. [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 1978. doi:10.1158/1538-7445.AM2014-1978
Abstract 198: Ex vivo expansion of hematopoietic stem cells in nonhuman primate using optimal cytokine combinations
Authors: Zhang Yu , Shen Bin , Ren Zhihua , Dai Wei , Ma Yupo , Jiang Yongping 
Published: May 2015

Abstract
Hematopoietic stem cell (HSC) or hematopoietic progenitor cell (HPC) transplantation has been widely accepted for the treatment of malignant blood diseases, as well as immunological disorders. Due to insufficient amounts of HLA-matched stem/progenitor cells, multiple strategies have been developed for expansion of hematopoietic stem cells ex vivo in the past. Here, we report for the first time that HSCs/HPCs from cynomolgus could be expanded at a high efficiency with an optimal cytokine combination. CD34+ cells were isolated from mobilized peripheral blood (PB) of cynomolgus (n=4) that had received a joint application of rhG-CSF (200 µg/kg) and rhSCF (200 µg/kg) s.c. for 5 (successive) days. Peripheral blood (15 ml each) was collected 24 and 48 h after the final injection of cytokines. A liquid suspension culture system that contained SCF, TPO, FL, IL-3, G-CSF and GM-CSF was employed for CD34+ cells expansion. We observed that PB-derived HSCs/HPCs underwent a significant expansion by day 15 of culture. Total nucleated cells were expanded for 1839 folds (Mean value) by day 33 whereas CD34+ cells increased about 80 folds (Mean value) by day 28. Further in vivo studies will be carried out to evaluate short-term and long-term engraftments of ex vivo expanded CD34+ cells. Nevertheless, our current study demonstrates that optimal cytokine combinations can be used for promoting CD34+ cell expansion efficiently ex vivo in a non-human primate model. This line of study is likely to provide an effective approach for expansion of human hematopoietic stem cells for various therapeutic applications.
Citation Format: Yu Zhang, Bin Shen, Zhihua Ren, Wei Dai, Yupo Ma, Yongping Jiang. Ex vivo expansion of hematopoietic stem cells in nonhuman primate using optimal cytokine combinations. [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 198. doi:10.1158/1538-7445.AM2014-198
Abstract 1987: The role of lipolysis-stimulated lipoprotein receptor in directing breast cancer cell behavior and subtype
Authors: Fleming Jodie M. , Reaves Denise K. , Fagan-Solis Katerina D. , Dunphy Karen , Oliver Shannon D. 
Published: May 2015

Abstract
The claudin-low molecular subtype of breast cancer is of particular interest for clinically the majority of these tumors are poor prognosis, triple negative, invasive ductal carcinomas. Claudin-low tumors are characterized by low gene expression of cell junction and adhesion proteins, and de-regulation of tight junction proteins is often been implicated in tumorigenesis. Herein, we sought to define the role of tricellular tight junction (tTJ) proteins in breast cancer and cancer cell behavior with a focus on lipolysis-stimulated lipoprotein receptor (LSR). LSR was expressed in epithelium, endothelium, adipose and stromal cells within the healthy breast tissue, as well as in tumor epithelium. LSR expression was significantly correlated with invasive ductal carcinomas compared to invasive lobular carcinomas, and ERα positive tumors and breast cancer cell lines. Consistent with the role of LSR in tTJs, LSR levels were significantly reduced in claudin-low breast cancer cell lines. Functional studies illustrated that that re-introduction of LSR into a claudin-low cell line suppressed the EMT phenotype and reduced individual cell migration. However, our data suggest that LSR may direct collective cell migration. Moreover, re-introduction of LSR in claudin-low breast cancer cell lines reestablished a family of TJ expression, thereby reverting claudin-low lines to other molecular subtypes. Overexpression of LSR enhanced proliferation and survival in anchorage independent conditions, suggesting that reestablishment of tight junctions is not sufficient to inhibit aggressive cell behaviors in vitro. Collectively, these data highlight an unanticipated role for the tTJ protein, LSR in directing aggressive breast cancer behavior.
Citation Format: Jodie M. Fleming, Denise K. Reaves, Katerina D. Fagan-Solis, Karen Dunphy, Shannon D. Oliver. The role of lipolysis-stimulated lipoprotein receptor in directing breast cancer cell behavior and subtype. [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 1987. doi:10.1158/1538-7445.AM2014-1987
Abstract 1991: Axl overexpression drives migration and invasion in colon cancer
Authors: Uribe Diana J. , Bosurgi Lidia , Gagliani Nicola , Joannas Leonel , Watson Adam , Martinez Jesse D. , Rothlin Carla V. , Ghosh Sourav 
Published: May 2015

Abstract
Receptor tyrosine kinases (RTK) of the TAM family have been described as oncogenes. Axl and Mertk, two members of the TAM family, are also potent negative regulators of the inflammatory response. Inflammation is an enabling characteristic of cancer hallmarks and can promote tumorigenesis and tumor progression. Genetic ablation of Axl and Mertk in mice, results in heightened inflammation in the gut and increased susceptibility to inflammation-driven colon cancer (azoxymethane/dextran sodium sulfate treatment paradigm). We sought to understand the role of Axl and Mertk, individually, in colon cancer cells to identify the key TAM oncogene in this disease.
Here we show that Axl, but not Mertk, was highly expressed and correlated with grade of metastatic colon cancer. Silencing Axl expression in RKO-AS45-1 and HCT116 colon cancer cells had no significant effect on proliferation and survival, but markedly decreased migration and invasion. R428, a selective Axl small molecule inhibitor, also drastically reduced migration in these colon cancer cell lines. Analyses of Axl knockout mice revealed that single, genetic ablation of this TAM RTK does not increase susceptibility to DSS-induced colitis, in contrast to that observed in Axl and Mertk double knockout mice.
These results are consistent with a redundant function of Axl and Mer in the regulation of the inflammatory response. Our findings suggest that the selective targeting of Axl in colon cancer might disable the oncogenic function of TAM RTKs, while sparing the protective, anti-inflammatory function of this RTK family in this disease.
Citation Format: Diana J. Uribe, Lidia Bosurgi, Nicola Gagliani, Leonel Joannas, Adam Watson, Jesse D. Martinez, Carla V. Rothlin, Sourav Ghosh. Axl overexpression drives migration and invasion in colon cancer. [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 1991. doi:10.1158/1538-7445.AM2014-1991
Abstract 1992: Y-box protein-associated acidic protein promotes breast cancer progression and is a potential molecular target
Authors: Scully Olivia J. , Thike Aye Aye , Yip George Wai-Cheong , Tan Puay Hoon , Matsumoto Ken , Bay Boon Huat 
Published: May 2015

Abstract
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 &lt;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
Abstract 1994: Cd44s is of functional importance for hepatocellular carcinoma (hcc) extra-hepatic metastases through activation of sdf-1a/cxcr4 axis
Authors: Zhu Wenwei , Guo Lei , Ye Qinhai 
Published: May 2015

Abstract
Background: CD44 has been reported as a promoter of metastasis in several tumors, including HCC. In this study, we elucidated the critical role of CD44 in HCC metastasis, especially in distant metastasis as well as the underling mechanism.
Methods: The expression of CXCR4, CD44 and their associated cellular signaling cascades, involving Akt and MAP Kinases, were determined by Western blotting. We also established CD44-deficient MHCC-97H cell lines by transfection with miRNA-CXCR4 plasmids and determined cell migration/invasion activity in a transwell assay.The prognostic value of CD44 and it's combination with CXCR4 was further evaluated.
Results: HCC patients with higher CD44 have poor prognosis, including reduced disease-free and overall survival, and individuals with distinct metastasis have higher frequency expression of CD44. We found that expression of CD44 was positively related to metastatic potential of HCC cell lines, and modified cells with CD44high showed higher aggressiveness in vitro, and higher metastatic ability in vivo. Furthermore, the mechanism of CD44 improving the invasion activity of HCC cells was though the SDF-1a/CXCR4 axis. CD44 can activate the PI-3K/Akt pathway through binding HA, which can up-regulate the expression of CXCR4. CD44 combined with CXCR4 is a promising independent predictor of tumor recurrence and survival in hepatocellular carcinoma patients.
CONCLUSIONS: CD44s is a potent predictor for extra-hapatic metastasis and overall survival of HCC patients. Our findings also provided evidence that the process of HA/CD44-induced CXCR4 expression is functional important for the invasiveness and metastasis of HCC. Therefore, the CD44-SDF-1α/CXCR4 system may be a new therapeutic target for treating HCC metastasis.
Note: This abstract was not presented at the meeting.
Citation Format: Wenwei Zhu, Lei Guo, Qinhai Ye. Cd44s is of functional importance for hepatocellular carcinoma (hcc) extra-hepatic metastases through activation of sdf-1a/cxcr4 axis. [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 1994. doi:10.1158/1538-7445.AM2014-1994
Abstract 2004: S100A4 in colorectal cancer - biological function of nuclear localization
Authors: Egeland Eivind V. , Boye Kjetil , Flatmark Kjersti , Pettersen Solveig J. , Oyjord Tove , Maelandsmo Gunhild M. 
Published: May 2015

Abstract
S100A4 is a Ca2+-binding protein promoting metastasis in several types of tumors. The protein possesses a wide variety of biological functions, and locates to different subcellular compartments including the nucleus, cytoplasm and extracellular space. Even though S100A4 is mainly localized in the latter two compartments, we have previosusly shown that the protein is localized to the nucleus in more aggressive forms of colorectal cancer (CRC) and that nuclear S100A4 has prognostic impact. This may suggest a function of nuclear S100A4 in the regulation of tumor progression and metastasis formation.
The CRC cell line SW620 shows heterogeneity in nuclear S100A4 expression and in preliminary experiments we sorted cells into three distinct phases of the cell cycle using Fluorescent-activated cell sorting (FACS). When comparing the phases, the G2/M cells showed increased accumulation of nuclear S100A4 compared to cells in the G1 and S phase, respectively. Further validation was done using treatment with the cell cycle inhibitors nocodazole or thymidine, followed by subsequent release of cells. Protein expression of S100A4 at selected time points after release did also show accumulation in the nucleus around the G2/M transition making this subcellular translocation interesting for further investigation. Cancer cells are known to have a dysfunctional cell division apparatus and these results made it tempting to speculate whether S100A4 may be involved in cell cycle regulation. To further study the functional importance of the nuclear expression two different approaches were followed.
First, CRC cells exclusively expressing S100A4 in the nucleus were made and used to identify downstream targets of nuclear S100A4. At the moment potential targets are being validated.
Furthermore, we searched for factors known to be associated with the G2/M phase. Of great interest, the Proximity Ligation Assay (PLA) demonstrated that S100A4 and Cyclin B1, an important regulator of the G2/M transition, are within the same protein complex, and we are currently in the process of further characterizing this interaction.
With clinical data linking nuclear expression of S100A4 with aggressive CRC, elucidation of the biological processes involved might unravel novel therapeutic possibilities.
Citation Format: Eivind V. Egeland, Kjetil Boye, Kjersti Flatmark, Solveig J. Pettersen, Tove Oyjord, Gunhild M. Maelandsmo. S100A4 in colorectal cancer - biological function of nuclear localization. [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 2004. doi:10.1158/1538-7445.AM2014-2004
Abstract 201: The combination treatment of TNF-α and poly (dA:dT) preactivated hMSCs with doxorubicin enhances antitumorigenic activity
Authors: Yoon Nara , Park Min Sung , Peltier Grant , Reneau John C. , Prockop Darwin J. , Prockop Darwin J. , Lee Ryang Hwa 
Published: May 2015

Abstract
Our recent study showed that human mesenchymal stem/stromal cells (hMSCs) were activated to express TRAIL by exposure to TNF-α. These TRAIL expressing hMSCs effectively induced apoptosis in MDA-MB-231 (MDA) cells in vitro and in vivo. TRAIL was further up-regulated by RNA released by dead MDA cells in a TLR3-dependent manner. Here, we show that the further increase of TRAIL in hMSCs was also mediated by feed-forward stimulation of AIM2 or IFIH1 by DNA and RNA released from dead MDA cells. Poly(dA:dT), a synthetic ligand for AIM2, most effectively activated hMSCs to express TRAIL and increased the killing efficacy of hMSCs in MDA cells compared to TNF-α or poly(I:C), a synthetic ligand for TLR3 or IFIH1. Furthermore, weekly infusions of hMSCs pre-activated with TNF-α and poly(dA:dT) effectively inhibited the progression of lung tumor formation in mice, compared to TNF-α pre-activated hMSCs. Such anti-tumorigenic effect of hMSCs upon activation with TNF-α and poly(dA:dT) was enhanced when combined with chemotherapeutic drug, doxorubicin and thereby, this combination treatment significantly reduced the size of tumor burden in mice compared to TNF-α pre-activated hMSC treatment. These results suggest that treatment of pre-activated hMSCs combined with doxorubicin enhances their tumor-suppressive properties and may provide a potential novel therapy for cancer treatment.
Citation Format: Nara Yoon, Min Sung Park, Grant Peltier, John C. Reneau, Darwin J. Prockop, Darwin J. Prockop, Ryang Hwa Lee. The combination treatment of TNF-α and poly (dA:dT) preactivated hMSCs with doxorubicin enhances antitumorigenic activity. [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 201. doi:10.1158/1538-7445.AM2014-201
Abstract 2014: SHP2 stabilizes EGFR and beta-catenin to promote the transformation and tumorigenic potential of basal-like and triple-negative breast cancer cells
Authors: Zhao Hua , Agazie Yehenew M. 
Published: May 2015

Abstract
Basal-like and triple-negative breast cancer (BTBC) causes disproportionately high mortalities in women. One of the major reasons is lack of targeted therapy, and the other is the highly aggressive and metastatic nature of the disease. The primary complication in finding viable drug targets has been the dysregulation of multiple signaling pathways, making one pathway inhibition an unlikely strategy to lead to effective treatment for BTBC. Therefore, targeting multiple pathways or finding proteins that control multiple signaling pathways and targeting them remain to be the only hope. In line with this, we have discovered that the Src homology phosphotyrosyl phosphatase 2 (SHP2) controls EGFR and Wnt/β-catenin signaling, major pathways known to be dysregulated in BTBC. We show that SHP2 overexpression in BTBC tumors is associated with elevated EGFR expression and cytoplasmic and nuclear accumulation of β-catenin. Silencing SHP2 expression in BTBC cells destabilizes EGFR and β-catenin and inhibits respective downstream signaling, confirming that SHP2 overexpression is essential for dysregulation of EGFR and β-catenin in this subtype of breast cancer. Furthermore, we demonstrate that inhibition of SHP2 in BTBC cells induces luminal epithelial morphology, suppresses cell proliferation, reverses transformation, blocks invasiveness in 3D matrigel, and abolishes tumorigenesis and metastasis. These findings suggest that SHP2 controls the EGFR and the Wnt/β-catenin signaling pathways to promote BTBC.
Citation Format: Hua Zhao, Yehenew M. Agazie. SHP2 stabilizes EGFR and beta-catenin to promote the transformation and tumorigenic potential of basal-like and triple-negative breast cancer cells. [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 2014. doi:10.1158/1538-7445.AM2014-2014