bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3783: Talin-1 phosphorylation promotes invasion and migration of prostate tumor cells through activation of β1 integrins.
Authors: Jin Jung-Kang , Lee Yu-Chen , Lin Sue-Hwa , Gallick Gary E. 
Published: August 2014

Abstract
Integrins have been shown to play a critical role in cell survival. We recently demonstrated that integrins are constitutively activated in highly metastatic prostate cancer cell PC3-mm2. Activation of integrins increases their binding affinity with extracellular matrix, resulting in increased migration and cancer metastasis. Talin is a 270 kDa cytoskeletal protein that has been shown to regulate integrin activity. Previous reports showed that the S425 residue in the N-terminal domain of talin was phosphorylated by Cdk5 to increase talin stability. In this study, we determined whether talin S425 phosphorylation regulates β1 integrin activation. We found that β1 integrin activation in prostate tumor cells correlates with talin S425 phosphorylation but not total talin levels. To examine the role of talin-pS425 in β1 integrin activation, endogenous talin-1 in PC3-mm2 cells was knocked down by shRNA, followed by re-expression of a phosphorylation-deficient S425A or phosphorylation-mimicking S425D talin-1 mutant. Re-expressing phosphorylation-deficient S425A-talin-1 in talin-1-knockdown PC3-mm2 cells showed reduced activation of β1 integrins, and decreased migration and invasion, compared to cells re-expressing wild type talin-1. In contrast, re-expressing the phosphorylation-mimicking S425D mutant in talin-1-knockdown PC3-mm2 cells restored β1 integrin activation and increased migratory and invasive properties of these cells. Inhibition of Cdk5 by roscovitine, a Cdk5 inhibitor, decreases talin-1 S425 phosphorylation and also inhibits downstream integrin signaling, including FAK and Src phosphorylation. Treatment of PC3-mm2 cells with roscovitine decreases β1 integrin activation and migration of PC3-mm2 cells. These results suggest that phosphorylation of talin-1 at S425 plays a role in promoting β1 integrin activation, leading to increased metastatic potential of prostate tumor cells.
Citation Format: Jung-Kang Jin, Yu-Chen Lee, Sue-Hwa Lin, Gary E. Gallick. Talin-1 phosphorylation promotes invasion and migration of prostate tumor cells through activation of β1 integrins. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3783. doi:10.1158/1538-7445.AM2013-3783
Abstract 3789: The alternatively spliced PRMT1 isoform PRMT1v2 promotes breast cancer cell survival and invasiveness.
Authors: Baldwin Robert Mitchell , Morettin Alan , Paris Genevieve , Goulet Isabelle , Cote Jocelyn 
Published: August 2014

Abstract
Breast cancer is the leading cause of cancer-related deaths in women. Despite intensive treatment to overcome this disease, recurrence is common and often incurable due to the highly aggressive nature of the recurrent tumour. Protein arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs) and plays an important role in many cellular processes. Aberrant PRMT expression has been observed in several common cancer types, however their precise contribution to the cell transformation process and cancer progression is not well understood. Previously, we reported that the PRMT1 gene generates several alternatively spliced isoforms and our initial biochemical characterization of these isoforms revealed that they exhibit distinct substrate specificity and sub-cellular localization. Here we have focused on the PRMT1v2 isoform, which is the only predominantly cytoplasmic isoform and has increased relative expression in breast cancer cell lines and tumours. Specific depletion of PRMT1v2 using RNA interference caused a significant decrease in breast cancer cell survival due to an induction of apoptosis. Furthermore, depletion of PRMT1v2 in MDA-MB-231, an aggressive breast cancer cell line, resulted in significantly decreased cell invasion. Alternatively, PRMT1v2 overexpression in a non-aggressive breast cancer cell line, MCF7, was sufficient to enhance their invasiveness. This novel activity is specific to PRMT1v2, as overexpression of other isoforms did not enhance invasion. It also requires both proper subcellular localization and methylase activity. Consistent with an invasive phenotype, PRMT1v2 overexpression caused altered cell morphology and reduced cell-cell adhesion. Finally, we observed a significant reduction in β-catenin protein levels, a critical cell-cell adhesion protein, and show that this reduction is pivotal to PRMT1v2-enhanced cell invasion. Our study underscores the importance of characterizing the distinct functional differences between PRMT1 isoforms. Overall, we demonstrate a specific role for PRMT1v2 in promoting breast cancer cell survival and invasion, and propose that it may represent a promising therapeutic target.
*RMB is a Postdoctoral Fellow of the Canadian Institute of Health Research
Citation Format: Robert Mitchell Baldwin, Alan Morettin, Genevieve Paris, Isabelle Goulet, Jocelyn Cote. The alternatively spliced PRMT1 isoform PRMT1v2 promotes breast cancer cell survival and invasiveness. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3789. doi:10.1158/1538-7445.AM2013-3789
Abstract 3793: S100A8/A9 promotes invasion and migration through p38 MAPK-dependent NF-κB activation in gastric cancer cells.
Authors: Kwon Chae Hwa , Moon Hyun Jung , Park Hye Ji , Choi Jin Hwa , Park Do Youn 
Published: August 2014

Abstract
S100A8 and S100A9 (S100A8/A9) are low-molecular weight members of the S100 family of calcium-binding proteins. Recent studies have reported S100A8/A9 promote tumorigenesis. We have previously reported that S100A8/A9 is mostly expressed in stromal cells and inflammatory cells between gastric tumor cells. However, the role of environmental S100A8/A9 in gastric cancer has not been defined. We observed in the present study the effect of S100A8/A9 on migration and invasion of gastric cancer cells. S100A8/A9 treatment increased migration and invasion at lower concentrations that did not affect cell proliferation and cell viability. S100A8/A9 caused activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). The phosphorylation of p38 MAPK was not affected by the NF-κB inhibitor Bay whereas activation of NF-κB was blocked by p38 MAPK inhibitor SB203580, indicating that S100A8/A9-induced NF-κB activation is mediated by phosphorylation of p38 MAPK. S100A8/A9-induced cell migration and invasion was inhibited by SB203580 and Bay, suggesting that activation of p38 MAPK and NF-κB is involved in the S100A8/A9 induced cell migration and invasion. S100A8/A9 caused an increase in matrix metalloproteinase 2 (MMP2) and MMP12 expression, which were inhibited by SB203580 and Bay. S100A8/A9-induced cell migration and invasion was inhibited by MMP2 siRNA and MMP12 siRNA, indicating that MMP2 and MMP12 is related to the S100A8/A9 induced cell migration and invasion. Taken together, these results suggest that S100A8/A9 promotes cell migration and invasion through p38 MAPK-dependent NF-κB activation leading to an increase of MMP2 and MMP12 in gastric cancer.
Citation Format: Chae Hwa Kwon, Hyun Jung Moon, Hye Ji Park, Jin Hwa Choi, Do Youn Park. S100A8/A9 promotes invasion and migration through p38 MAPK-dependent NF-κB activation in gastric cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3793. doi:10.1158/1538-7445.AM2013-3793
Abstract 3795: Vangl2 and Prickle1 expression, interaction and regulation of Wnt/PCP signaling in medulloblastoma and neuroblastoma.
Authors: Dyberg Cecilia H. , Papachristou Panagiotis , Lagercrantz Hugo , Johnsen John I , Wickström Malin 
Published: August 2014

Abstract
Background /Aims: Wnt are a family of intercellular signaling factors that regulates a wide range of functions during embryonic development including cell proliferation, cell fate determination, differentiation, cell polarity and cell migration. They bind to Frizzled receptors and thereafter proceed via Dishevelled to several intracellular pathways known as the canonical and non-canonical signaling pathways. Activation of the canonical pathway results in an accumulation of cytoplasmic beta-catenin levels. Increased Wnt/beta-catenin signaling is associated with many forms of cancer, including the embryonic neural childhood tumors medulloblastoma and neuroblastoma. The non-canonical Wnt signaling pathways can inhibit the canonical signaling pathway, although the mechanism is still unclear. In this study, we investigate the roles of Prickle1 and Van Gogh-Like 2 (Vangl2), two planar cell polarity (PCP) genes in regulation of the cytoskeleton, Wnt/beta-catenin activity and tumorigenicity in neuroblastoma and medulloblastoma.
Methods: mRNA and protein expression of human Prickle1, Vangl2 and beta-catenin were examined in neuroblastoma and medulloblastoma cell lines. siRNA and cDNA transfection were performed together with co-immunoprecipitation and immunocytochemistry.
Results and conclusions: We show that Prickle1 and Vangl2 are expressed in neuroblastoma and medulloblastoma cell lines at different levels. Decreased Prickle1 expression correlates with increased levels of Wnt/beta-catenin in both medullo- and neuroblastoma cell lines, demonstrating a downregulation of PCP components and a possible activation of the canonical Wnt signaling pathway. Immunoprecipitation demonstrated that Prickle1 is present in complex with Vangl2. However, the exact mode of interaction between Prickle1 and Vangl2 remains to be eluciated. Microarray analysis revealed that low expressions of Prickle1 or Vangl2 are both associated significantly worse clinical outcome in neuroblastoma. Additionally, siRNA experiments revealed that knockdown of Prickle1 and Vangl2 increased cell proliferation of neuroblastoma cells. Taken together this indicate that the non-canonical Wnt pathway may be an interesting therapeutic target in embryanol neural childhood tumors.
Citation Format: Cecilia H. Dyberg, Panagiotis Papachristou, Hugo Lagercrantz, John I Johnsen, Malin Wickström. Vangl2 and Prickle1 expression, interaction and regulation of Wnt/PCP signaling in medulloblastoma and neuroblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3795. doi:10.1158/1538-7445.AM2013-3795
Abstract 3796: Endophilin II promotes breast tumor progression and metastasis.
Authors: Baldassarre Tomas , Meens Jalna , Craig Andrew W. 
Published: August 2014

Abstract
Invadopodia are filamentous actin-based membrane protrusions with extracellular matrix (ECM) degrading activity that are implicated in tumor progression and metastasis. A key step in invadopodia formation involves the recruitment of the membrane type 1 matrix metalloprotease (MT1-MMP) to invadopodia precursors. Surface expression of MT1-MMP promotes ECM degradation and cell invasiveness, and this is dependent on Src kinase-induced phosphorylation and inhibition of endocytic proteins. In fibroblasts, MT1-MMP internalization was regulated by Endophilin II (Endo II), a widely expressed protein implicated in synaptic vesicle uncoating and recycling in neurons. Here, we tested the role of Endo II in invadopodia formation in basal-like breast cancer cells, and in tumor progression and metastasis in mice. High levels of Endo II expression were observed in basal breast cancer cell lines with high Src kinase and ECM-degrading activity. Immunohistochemistry staining also identified Endo II expression in primary breast tumors and lymph node metastases. To define the functions of Endo II, we achieved stable silencing of Endo II in two basal breast cancer cell lines (MDA-MB-231, HCC1806). Although Endo II was not required for uptake of receptors via clathrin-mediated endocytosis (EGFR, TfR), we observed a significant reduction in numbers of invadopodia and ECM degradation upon Endo II silencing. Consistent with invadopodia defects in vitro, Endo II silencing led to a significant reduction in tumor growth and metastases in mouse orthotopic tumor xenografts assays performed with both basal breast cancer cell models. This study provides novel insights into roles of Endo II as a positive regulator of invadopodia and basal breast cancer metastasis.
Citation Format: Tomas Baldassarre, Jalna Meens, Andrew W. Craig. Endophilin II promotes breast tumor progression and metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3796. doi:10.1158/1538-7445.AM2013-3796
Abstract 3798: Heat shock cognate protein HSPA8 (Hsc70) regulates migration and xenograft growth of breast tumor cell lines.
Authors: Pino Maria F. , Zhang Ge , Rosser Charles J. , Goodison Steve , Urquidi Virginia 
Published: August 2014

Abstract
In order to identify genes involved in the metastatic phenotype we had previously developed isogenic cell lines from the human breast carcinoma cell line MDA-MB-435 that have different metastatic phenotypes in immunocompromised mice. Proteomic profiling of the extracellular component of this model identified the heat shock cognate protein HSPA8 (Hsc70) as over-expressed in the metastatic cell line (M4A4) relative to its non-metastatic counterpart (NM2C5). Heat shock proteins are primarily implicated in a cytoprotective role when cells are exposed to stressful stimuli. They are intracellular molecular chaperones but are also found in the surface of embryonic stem cells and a variety of tumor cells. With the purpose of investigating the role of HSPA8 in tumor growth and metastasis, we first verified that this protein was expressed on the cell surface and in the conditioned medium of M4A4 cells, in addition to its intracellular location. Then we generated stable HSPA8 knockdown clones of the M4A4 cells and cell behavior was tested in a panel of analyses in vitro and xenograft growth was tested in immunocompromised mice. Knockdown of HSPA8 expression in M4A4 cells resulted in reduction of cell doubling time and of their migration potential in vitro. When individual M4A4-HSPA8 knocked down cell clones were injected into the mammary fat pad of immunocompromised mice significant reduction of the tumor size was observed relative to non-silencing control cells. The invasive and metastatic potential of the M4A4-HSPA8 knockdown clones as well as their transcriptional profile are currently under investigation. Our findings suggest that HSPA8 plays a role in cell growth in vitro and in vivo and may be involved in metastasis of breast cancer cells. Extracellular heat shock proteins have recently been shown to mediate a range of powerful effects in inflammatory, neuronal and immune cells through a number of cell surface receptors. The mechanisms involved in tumor dissemination and metastasis are potential targets for therapeutic intervention
Citation Format: Maria F. Pino, Ge Zhang, Charles J. Rosser, Steve Goodison, Virginia Urquidi. Heat shock cognate protein HSPA8 (Hsc70) regulates migration and xenograft growth of breast tumor cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3798. doi:10.1158/1538-7445.AM2013-3798
Abstract 3799: HTS performance and high-content analysis of antimigratory compound phenotypes using the Oris Pro 384 cell migration assay.
Authors: Fronczak Jennifer , Vollmer Laura , Krishnan Gopal , Vogt Andreas 
Published: August 2014

Abstract
The discovery of anti-metastatic agents that inhibit cancer cell motility has been hindered by a dearth of high-throughput screening (HTS) -compatible cell motility assays. The Oris™ Pro 384 well cell migration assay, developed by Platypus Technologies, is an innovative cell motility assay designed to enable HTS of potential anti-cancer compounds and wound healing agents on adherent tumor and endothelial cell lines. The assay utilizes a centrally located, non-toxic, biocompatible gel (BCG) to form a uniformly sized, cell-free detection zone into which cells migrate. The assay is logistically simple and does not require any mechanical processing steps, such as cell wounding or removal of physical barriers. The assay is fully compatible with laboratory automation, including robotic liquid handlers, plate washers, and high-content screening (HCS) readers.
A formal investigation of the accuracy, robustness, and HTS performance of the assay was conducted following guidelines in place at the University of Pittsburgh Drug Discovery Institute (UPDDI). Using MDA-MB-231 human breast cancer cells, the assay was optimized for migration kinetics, cell seeding density, and DMSO tolerance. In multi-day variability studies, the assay delivered signal-to-background ratios &gt; 10 and Z-factors above 0.5 on three consecutive days, was insensitive to process errors or edge-effects, and passed UPDDI Assay Protocol Approval Committee (APAC) criteria. The assay delivered equal HTS performance on two different HCS platforms – the Thermo Scientific Cellomics ArrayScan II and the Molecular Devices ImageXpress®Ultra point scanning confocal reader. Screening of a test cassette of 1280 compounds with known biological activities identified several agents with mechanisms associated with cell motility. The multiparametric nature of the HCS assay permitted correlation of antimigratory activity with cellular toxicity. Our results validate the Oris™ Pro 384 cell migration assay as a logistically simple and information-rich cell motility analysis platform that meets the demands of large scale compound screening.
Citation Format: Jennifer Fronczak, Laura Vollmer, Gopal Krishnan, Andreas Vogt. HTS performance and high-content analysis of antimigratory compound phenotypes using the Oris Pro 384 cell migration assay. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3799. doi:10.1158/1538-7445.AM2013-3799
Abstract 380: Serine-Arginine protein kinase 1 (SRPK1) - A potential target of angiogenesis in prostate cancer.
Authors: Mavrou Athina , Oltean Sebastian , Bates Dave 
Published: August 2014

Abstract
Angiogenesis is required for all tumors to grow and metastasize and is mainly induced by the vascular endothelial growth factor (VEGF). Alternative spliced isoforms associated with cancer progression have been described in all areas of hallmarks of cancer, including angiogenesis. VEGF mRNA is alternatively spliced at the terminal exon, to produce two families of isoforms. The pro- angiogenic family, VEGFxxx, was shown to be up-regulated in all cancers studied so far, where as the anti- angiogenic family is preferentially expressed in normal non-angiogenic tissues, but down-regulated in most cancers. One of the factors involved in the regulation of VEGF alternative splicing is SRPK1. This is a protein kinase that phosphorylates the splicing factor SRSF1 and favours the production of the pro-angiogenic VEGF isoform. We therefore tested the hypothesis that down - regulation of SRPK1 in prostate cancer cells would increase the production of the anti-angiogenic isoform, preventing angiogenesis and tumor growth.
PC-3, DU145 and LnCap prostate cancer cells showed an increased expression of SRPK1 when compared to Primary Prostate epithelial cells. Stable SRPK1 knock-down (KD) in PC-3 and LnCap prostate cancer cells was obtained using a lentiviral system (Dharmacon). This resulted in a reduction in splice factor expression, mainly SRSF1, and induced a switch in the expression of VEGF towards the anti-angiogenic isoform, VEGF165b, when compared to control cells (transfected with non-targeting shRNA). PC-3 SRPK1 KD and control cell lines were injected subcutaneously in male nude mice. Knock down of SRPK1 resulted in an inhibition of tumour growth, as shown by the significant difference in tumor size between the SRPK1 KD (250.0 ± 82.28 n=9) and control cell line (994.7 ± 243.5 n=9)(Day 29 post-injection). In addition to the reduction in tumor volume, SRPK1 inhibition resulted in decrease in vascular density of the tumors, as shown by the significant reduction in blood vessel number in PC-3 SRPK1 KD (2.714 ± 0.3686 n=7) mice compared with control (4.292 ± 0.5426 n=8). These in vitro and in vivo data suggest that the regulation of VEGF splicing by SRPK1 alters prostate cancer tumour growth and angiogenesis.
Citation Format: Athina Mavrou, Sebastian Oltean, Dave Bates. Serine-Arginine protein kinase 1 (SRPK1) - A potential target of angiogenesis in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 380. doi:10.1158/1538-7445.AM2013-380
Abstract 3800: Osteonectin suppresses proliferation and migration of human prostate cancer cells.
Authors: Shin Minkyoung 
Published: August 2014

Abstract
Osteonectin/SPARC(Secreted Protein Acidic and Rich in Cysteine)/BM-40 is an extracellular protein that has been studied in ECM(Extra Cellular Matrix) organization, immune modulation, proliferation, adhesion, invasion and migration in various cancers. Advanced prostate cancer (PCa) is significantly affected by cross-talk among cancer cells, stromal cells and ECM. Such communication is particularly could contribute to migration and invasion of prostate cancer cells. However, the precise mechanism in migration and invasion of PCa cells are poorly understood. In this report, we investigated the effect of osteonectin on proliferation, migration and invasion of PCa cells. Indeed, Prostate-derived stromal cells (PrSC) has been shown to express high mRNA levels of osteonectin and secret relatively high levels of osteonectin. We revealed that osteonectin from PrSC and refined osteonectin protein also inhibited activation of AKT-p21 signaling, which plays an important role in prostate cancer cell growth, and affected down-regulation of migration and invasion of LNCaP cells. Together, these studies support a conclusion that interaction of stromal cells and PCa cells as osteonectin play an important role in progression of prostate cancer.
Citation Format: Minkyoung Shin. Osteonectin suppresses proliferation and migration of human prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3800. doi:10.1158/1538-7445.AM2013-3800