bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2305: Role of ST3Gal1 sialyltransferase in breast cancer cells
Authors: Fan Tan-chi , Lin Wen-der , Chang Chih-hao , Chang Lan-yi , Chen Zhin-mei , Khoo Kay-hooi , Yu Alice 
Published: June 2012

Abstract
Alteration of glycan structures on glycoproteins or glycolipids is a common phenomenon observed in malignancy. The premature sialylation of core carbohydrate structure leading to shorter truncated glycans has been well documented. Mucin O-glycans from normal breast are mostly composed of elongated core 2 structures. It has been shown that MUC1 O-glycans from breast cancer cell lines are often truncated and mainly consist of core 1-based structures from mass spectrometry sequencing. It may be due to down-regulated C2GnT (core 2 enzymes) or increased sialyltransferase activities which add sialic acid in an α2,3 linkage to Galβ1-3GalNAc, producing sialyl3 T antigen, which is no longer recognized by C2GnT as a substrate donor. Six different α2,3-sialyltransferases catalyze the transfer of sialic acids to Gal. Among which, ST3Gal1 and ST3Gal2 are capable of producing sialyl3 T antigens; however, only the expression of ST3Gal1 mRNA is elevated in primary breast carcinoma cells compared to normal or benign breast tissues. In ductal carcinomas, the expression of ST3Gal1 appeared to correlate with histology grade. However, not much is known about the role of ST3Gal1 in breast cancers. We investigated the role of ST3Gal1-mediated sialylation in the function of proteins and further characterize the molecular mechanism underlying ST3Gal1-mediated cancer metastasis.
To confirm the relationship of ST3Gal1 expression in breast cancers, we performed qPCR analysis of sialyltransferase gene expression in 93 breast cancer patients. ST3Gal1 expression was statistically higher in ER-, PR-, and HER2-negative category (p&lt;0.037). Using MALDI-MS analysis, the glycome profiles showed that ST3Gal1 silencing in MDA-MB-231 breast cancer cells resulted in reduced α2,3-linked sialic acid-containing O-glycosylation including sialyl3T antigen, without significant differences in N-glycosylation. We observed that ST3Gal1 silenced MDA-MB-231 cells have the tendency to aggregate compared to control cells. To test the hypothesis that decrease of sialylation in beast cancer cells will affect the metastatic behavior, cell migration and invasion were assayed. Indeed, Transwell migration of ST3Gal1 silenced MDA-MB-231 significantly decreased to ∼30% of control cells. More strikingly, the Transwell invasion of ST3Gal1 silenced cells were down-regulated to less than 10% of control cell. Furthermore, the enzyme activities of MMP9 and m-calpain which are known to regulate the invasion ability of cancer cells were both down-regulated upon silencing of ST3Gal1. In conclusion, these data strongly suggest that cell surface α2,3-sialylation contributes to breast cancer cells invasiveness.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2305. doi:10.1158/1538-7445.AM2011-2305
Abstract 2316: Therapeutic targeting of novel human stem cell and cancer associated glycans
Authors: Saunders Mary R. , An Hyun Joo , Olivos David J. , Maeda Yoshiko , Lim Ryan G. , Lebrilla Carlito B. , Lam Kit S. 
Published: June 2012

Abstract
Host and tumor surface glycans are important in regulating pivotal pathophysiological events during the development of cancer and tumor progression. Changes in glycosylation allow tumorigenic cells to seize control over developmental processes which allow cells to proliferate, invade, promote angiogenesis, and metastasize. Malignant transformation is accompanied by the expression of oncofetal antigens which are expressed on embryonic cells, tumor cells, and a few adult cells. Glycans common to human embryonic stem cells and cancer cells can be targeted using combinatorial chemistry. Several peptidomimetic ligands have been discovered using One Bead One Compound (OBOC) and One Bead Two Compound (OB2C) methods. These cell adhering ligands possess the potential to target tumorigenic cells and mediate intracellular signaling events by binding to high mannose glycans expressed on the surface of Jurkat, TK6, Her2 expressing MCF7, chemoresistant MCF7, HeLa, and SiHa cell lines. Three lead linear peptides with alternating natural and unnatural amino acids have been investigated for their in vivo targeting potential in the lymphoid leukemia, breast, and cervical cancer mouse xenograph models. In vitro and in vivo stem and cancer cell experiments, which demonstrate genetically altered glycan function, are currently being investigated for their anticancer potential. These novel agents may be used alone or in combination with chemoradiation and anti-angiogenesis strategies for treating cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2316. doi:10.1158/1538-7445.AM2011-2316
Abstract 2328: 15N-backbone and side-chain dynamics of the mutant calcium-binding protein S100B D63N
Authors: Liriano Melissa , Varney Kristen M. , Ishima Rieko , Weber David J. 
Published: June 2012

Abstract
Similar to calmodulin and other EF-hand-containing proteins, S100 proteins have no inherent enzymatic activity and perform their biological functions via calcium-dependent protein-protein interactions. Elevated protein levels of S100B have been linked to various types of cancers, including malignant melanomas, glioblastomas, and anaplastic astrocytomas. In the case of malignant melanomas, S100B contributes to cell proliferation by binding to p53 and inhibiting its tumor suppressing properties. However, one property of S100 proteins, including S100B, is that it only binds to calcium tightly when its target protein is bound, a feature that drug design studies for restoring p53 in melanoma must mimic. Therefore, the purpose of this study is to determine the mechanism for how target protein binding to S100B causes an increase in calcium-binding affinity. Previous studies suggest that the increase in calcium affinity in the presence of target is not the result of a structural modification. As an alternative explanation, the mechanism behind this event may involve a reduction in the ligand dynamics coordinating calcium in the canonical EF-hand when target peptide is present. To test this hypothesis with S100B, an asparagine mutant was made in order to have an 15N-probe in the tight-binding EF-hand of S100B for NMR side-chain dynamics with and without target peptide. 15N backbone dynamic experiments (T1, T2, and hetNOE) were collected for the S100B D63N mutant (+/- TRTK-12) at two magnetic fields to determine the effects of peptide binding at multiple time scales. Relaxation dispersion experiments were also collected for backbone and side-chain amides of S100B in the presence and absence of TRTK-12. For the backbone dynamic experiments, motion was detected in the hinge region and C-terminus of helix-4 at multiple timescales in the absence of TRTK-12 (ns-sec timescale). A similar profile was observed for those backbone residues undergoing motion in the chemical exchange time scale seen with the relaxation dispersion data. However, when a molecular target was introduced, the majority of these backbone amides that make up the hydrophobic pocket displayed a general decrease in dynamics. Side chain dynamics in the EF-hand was appreciated in the absence of TRTK-12 peptide, however when the target was present, no chemical exchange was seen with the 15N-D63N probe in the EF-hand. These findings imply that In the presence of target peptide, S100 proteins undergo a decrease in protein dynamics that translates from the site of target binding to the EF-hand.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2328. doi:10.1158/1538-7445.AM2011-2328
Abstract 2330: Role of RET finger protein in the integrin beta1 expression in cancer cells and its significance in cancer patients
Authors: Kato Takuya , Enomoto Atsushi , Asai Naoya , Murakumo Yoshiki , Takahashi Masahide 
Published: June 2012

Abstract
Integrins play central roles in the biology by regulating cell adhesion to the extracellular matrix and cell migration, growth, differentiation and apoptosis. Although contribution of integrins on cancer development has been well studied, the mechanism of the regulation of integrins expression remains elusive. Here we report that RET finger protein (RFP) regulates integrin beta1 expression in cancer cells. RNAi-mediated depletion of RFP resulted in decrease of integrin beta1 expression and impaired cell migration/invasion. RNA immunoprecipitation assay revealed that RFP interacts with integrin beta1 mRNA, and RFP knockdown caused destabilization of the mRNA. Furthermore, we examined the expression of RFP in human colon cancer and endometrial cancer, and assessed its clinical significance. High levels of RFP expression correlated with poor clinical outcome in colon cancer and endometrial cancer patients. These findings suggest that RFP regulates the cancer cell migration/invasion through the upregulation of integrin beta1 expression by stabilization of its mRNA, and expression of RFP can be a prognostic marker for an unfavorable clinical outcome in patients with colon cancer and endometrial cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2330. doi:10.1158/1538-7445.AM2011-2330
Abstract 2336: SFRP4 expression as a marker of invasion in gastric cancer
Authors: Busuttil Rita A. , George Joshy , Scott Kylie , Tan Patrick , Lade Stephen , Bowtell David D. , Boussioutas Alex 
Published: June 2012

Abstract
Gastric cancer (GC) is the fourth most common cancer in the world with approximately 1 million patients being diagnosed annually and is the second highest cause of cancer related deaths worldwide resulting in 700,000 deaths per year. The advanced stage at diagnosis and limited curative treatments for this stage of disease explains the mortality rate for GC. Early and late GC can usually be differentiated by their T-stage, which is a measure of invasion of the tumour through the gastric wall. T1 tumours exhibit minimal invasion whilst T4 tumours have invaded into adjacent structures.
Through our genomic research we have identified SFRP4 as a gene that is consistently over-expressed in gastric cancer when compared to normal gastric tissue, particularly advanced stage cancer. Its gene expression levels are directly proportional to the degree of invasion suggesting a potential role in this process. Analysis of the clinical data in conjunction with the genomics data shows that elevated levels of SFRP4 have also been correlated with poor prognosis in patients with GC independent of their T-stage.
We have used shRNA knockdown of SFRP4 in a gastric cell line to validate these findings in vitro. The invasive phenotype is able to be restored in these cells with the addition of recombinant SFRP4 protein. Evidence from this study suggests that SFRP4 plays a role in invasion which is a fundamental property of all cancers. In vivo studies are currently underway to determine whether the functional effects of SFRP4 observed in vitro in gastric cancer lines can be recapitulated in vivo.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2336. doi:10.1158/1538-7445.AM2011-2336
Abstract 2345: Identification of epithelial stromal interaction 1 as a novel target of KLF8
Authors: Li Tianshu , Lu Heng , Wang Xianhui , Yu Lin , Zhao Jihe 
Published: June 2012

Abstract
Epithelial stromal interaction 1 (EPSTI1) is a recently identified novel gene with two splicing variants that is highly upregulated in breast cancer cells when co-cultured with the stromal fibroblasts and in invasive breast carcinomas as compared with normal breast biopsies. The regulation and function of EPSTI1 are largely unknown. Interestingly, our microarray studies showed that EPSTI1 is one of the most upregulated genes in MCF-10A cells expressing ectopic Kruppel-like factor 8 (KLF8), a transcriptional factor is highly over-expressed in breast cancer and critical for cell cycle progression, oncogenic transformation, epithelial to mesenchymal transition (EMT) and metastatic progression of breast cancer. Real time qRT-PCR and western blotting demonstrated that EPSTI1 mRNA and protein levels are upregulated in a panel of invasive breast cancer cell lines that are known for aberrant overexpression of KLF8 as compared to noninvasive cell lines. Promoter reporter analysis indicated that KLF8 may activate EPSTI1 gene promoter. These results identified EPSTI1 as a novel target of KLF8 and suggest that EPSTI1 may play an important role for KLF8 signaling in the regulation of breast cancer invasion and metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2345. doi:10.1158/1538-7445.AM2011-2345
Abstract 2357: The TROY/TNFRSF19 receptor is overexpressed in human glioblastoma multiforme and regulates glioma cell survival via the NFkB pathway activation
Authors: Tuncali Serdar M. 
Published: June 2012

Abstract
Glial tumors progress to malignant grades by heightened proliferation and aggressive invasion of the surrounding normal brain. Understanding the genetic and biochemical processes that foster these behaviors is likely to reveal specific and effective targets for therapeutic intervention. We have identified TROY / TNFRSF19 as a novel transmembrane receptor that is overexpressed in glioblastoma multiforme. TROY is an orphan member of the tumor necrosis factor receptor (TNFR) superfamily that lacks a cytoplasmic death domain. Our previous data demonstrates that the level of TROY mRNA expression directly correlates with increasing glial tumor grade and inversely with overall patient survival. In addition, TROY overexpression in glioma cells activates Rac1 signaling in a Pyk2-dependent manner to drive invasion and migration. Here, we show that TROY over-expression enhances glioma cell survival against chemotherapy-induced cell death. TROY expressing glioma cells also displayed an increased resistance to temozolomide (TMZ) treatment. Conversely, siRNA mediated-depletion of TROY expression enhanced TMZ-induced cell death. To investigate the mechanism of TROY-induced cell survival, we surveyed a panel of known cancer signaling pathways by immunoblot analysis of cell lysates from untransfected glioma cells and lysates from glioma cells overexpressing TROY. Of the signaling pathways surveyed, we observed an increased activation of the Akt and NFκB pathways in TROY overexpressing cells relative to the untransfected cells. Inhibition of the NFκB pathway by expression of the super-repressor IκBα mutant abrogated TROY-induced cell survival to TMZ treatment. Similarly, inhibition of the Akt pathway by treatment of cells with the pharmacological inhibitor, LY294002, increased TMZ-induced cell death in TROY expressing cells. Together, these data indicate that TROY-stimulated glioma cell migration and invasion increases resistance to chemotherapy-induced cell death in glioma. Understanding the function of TROY in glioma biology may lead to the development of effective therapies against invasive gliomas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2357. doi:10.1158/1538-7445.AM2011-2357
Abstract 2358: Molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer
Authors: Chiu Ching-Chi , Cheng Ann-Joy 
Published: June 2012

Abstract
Purpose: The goal of this study was to establish a common set of molecules that regulate cell invasion in head and neck cancer (HNC). Experimental design: Five invasive sublines derived from HNC cell lines were established using the Matrigel selection method. Proteomic technology, MetaCore™ algorithm, and RT-PCR methods were used to search for molecules that contribute to the invasion phenotype. Cellular functional analyses and clinical association studies were applied to examine the significance of the molecules. Results: Fifty-two proteins were identified in more than two of the four independent proteomic experiments, including 10 (19%) molecular chaperones. Seven chaperones were confirmed to be differentially expressed in five sublines: Hsp90α, Hsp90β, Hsp90-B1/Gp96, Hsp70-A5/Grp78, HYOU1 up-regulation, while Hsp60 and GANAB down-regulation. Four molecules with the highest differential expressions (&gt; 4-fold) were further investigated. In all cell lines, knockdown of Hsp60 or GANAB and silencing of Gp96 or Grp78 considerably enhanced or reduced cell migration and invasion, respectively. Clinical association studies consistently revealed that low levels of Hsp60 or GANAB and high levels of Gp96 or Grp78 are significantly associated with advanced cancer (P&lt;0.001 to P = 0.047, respectively, for the four molecules) and poor survival (P&lt;0.001 to P=0.025, respectively, for the four molecules). Conclusion: In conclusion, our study defined molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer. Loss of the tumor suppression function of Hsp60 or GANAB and acquisition of the oncogenic function of Gp96 or Grp78 contribute to aggressive cancers. These molecules may serve as prognostic markers and targets for cancer drug development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2358. doi:10.1158/1538-7445.AM2011-2358
Abstract 2360: Dimethyl sulfoxide induces upregulation of tumor suppressor HLJ1 through activator protein-1 activation in human lung adenocarcinoma CL1-5 cells
Authors: Wang Chi-Chung , Lin Ai-Me , Lai Yi-Hua , Lin Sheng-Yi , Yang Pan-Chyr , Chen Jeremy J. W. 
Published: June 2012

Abstract
Dimethyl sulfoxide (DMSO) is an amphipathic molecule and has a diversity of antitumor activities. Previous studies demonstrated that DMSO could modulate AP-1 activity and lead to cell cycle arrest at G1 phase. HLJ1 is a newly identified tumor and invasion suppressor that inhibits tumorigenesis and cancer metastasis. Its transcriptional activity is also regulated by transcription factor AP-1. However, the effect of DMSO on HLJ1 is still unknown. In this study, low-HLJ1 expressing highly invasive CL1-5 lung adenocarcinoma cells were subjected to DMSO treatment. We found that DMSO can significantly inhibit cancer cell invasion and migration capabilities through up-regulation of HLJ1 in a concentration-dependent manner. In addition, knockdown of HLJ1 expression by siRNA was able to block the effects of DMSO-induction. The HLJ1 promoter and enhancer reporter assay revealed that DMSO transcriptionally upregulates HLJ1 expression through an AP-1 site within the HLJ1 enhancer. Furthermore, AP-1 subfamily members, JunD and JunB, were significantly upregulated by DMSO in a concentration-dependent manner. In conclusion, our results suggest that DMSO could be an important stimulator of the tumor suppressor protein, HLJ1, through AP-1 activation in highly invasive lung adenocarcinoma CL1-5 cells. Our findings provide some important information for further investigations to develop new drugs such as DMSO-derived analogues which may inhibit cancer invasion and progression by targeting HLJ1.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2360. doi:10.1158/1538-7445.AM2011-2360
Abstract 2379: Cyclin D3 is important for ErbB2-induced mammary cancer initiation and progression in the absence of Cyclin D1
Authors: Zhang Qian , Sakamoto Kazuhito , Triplett Aleata A. , Lin Wan-chi , Creamer Bradley A. , Wagner Kay-Uwe 
Published: June 2012

Abstract
The cell cycle regulatory protein Cyclin D1 has been reported to be essential for both normal mammary gland development during pregnancy and the malignant transformation of the mammary epithelium in response to receptor tyrosine kinase (RTK) signaling. We have recently reported that the prolactin receptor-associated kinase Jak2 controls the transcriptional activation and, more importantly, the nuclear accumulation of Cyclin D1 in normal mammary epithelial cells via expression and activation of Akt1. We also demonstrated that the functional ablation of Jak2 and Stat5 in ErbB2-expressing mammary epithelial cells protects against the onset of mammary tumorigenesis. Jak2, however, is not required for the survival and proliferation of neoplastic cells. The constitutive activation of ErbB2 signaling, which is an initial event in the formation of mammary cancer in this model, was able to override the functional role of Jak2 in regulating the expression of Akt1 and Cyclin D1. To further define the role of the downstream effector Cyclin D1 during cancer initiation and progression in response to Jak2 and RTK signaling, we generated an ErbB2-associated mammary cancer model that allows a functional ablation of Cyclin D1 either prior to or following neoplastic transformation. Surprisingly, and in sharp contrast to previous reports, nearly all Cyclin D1-deficient females expressing wildtype ErbB2 developed mammary tumors. While Cyclin D1 deficiency extended the tumor-free survival, this particular cell cycle regulatory protein was clearly not required for tumor maintenance and progression. Growth and proliferation of the vast majority of Cyclin D1-deficient primary mammary cancers was accompanied by an upregulation of Cyclin D3. Since Cyclin D2 expression remained very low, knocking down the last remaining D-type cyclin (i.e. Cyclin D3) in tumor-derived primary cancer cells using three different shRNA constructs was sufficient to attenuate the proliferation rates. Interestingly, the ablation of the pool of all three D-type cyclins did not result in an upregulation of Cyclin E. Collectively, the results of this study show that Cyclin D1 is dispensable for neoplastic transformation of mammary epithelial cells and it might therefore not serve as a sole therapeutic target to treat ErbB2-associated breast cancers as previously suggested. In addition, these observations indicate that Cyclin D1 is most likely not the only downstream effector of Jak2 signaling that mediates the protective effects of a functional ablation of Jak2 in ErbB2-induced mammary carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2379. doi:10.1158/1538-7445.AM2011-2379