bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5384: Hrev107 enhances prostaglandin D2 synthase-mediated cancer cells suppression in the testis.
Authors: Tsai Fu-Ming , Wu Chang-Chieh , Shyu Rong-Yaun , Jiang Shun-Yuan 
Published: August 2014

Abstract
Hrev107, also called HRASLS3 or PLA2G16, is a member of the HREV107 type II tumor suppressor gene family which includes HREV107, Retinoid-inducible gene 1 (RIG1), and HRASLS. The protein in this family contains an NC domain, with unknown function at the N-terminus, and a hydrophobic membrane-anchoring domain at the C-terminus. HREV107 has shown that expressed at high levels in differentiated tissues of post-meiotic testicular germ cells but not in human testicular germ cell tumors. Prostaglandin D2 (PGD2) has shown that can induce SOX-9 nuclear translocation and subsequent Sertoli cell differentiation. In addition, expression of the Prostaglandin D2 synthase (PTGDS) has been detected in the cellular lineage. This gives rise to the Sertoli cells, and the Sertoli cells appear to express the PTGDS only during the VI-VIII stages of the spermatogenic cycle after spermiation. These results suggested that PGD2 may play an important role in the testis differentiation. Our previous result showed that RIG1 (as RIG1 is expressed in the human species only) can interact with PTGDS. We further examined the effect of mouse Hrev107 on the growth of mouse testicular cells. When Hrev107 was expressed in TM3 or TM4 mouse testicular cancer cells, the cell migration and invasion were inhibited. Further, we found PTGDS was co-localized with Hrev107 in TM4 testis cells. In Hrev107-expressing NT2/D1 cells, elevated levels of PGD2, cAMP, and SRY-related high-mobility group box 9 (SOX9) were observed. This result indicated that Hrev107 can enhance PTGDS activity. Silencing of PTGDS expression significantly decreased h-REV107-mediated cAMP and PGD2 production. Furthermore, silencing of PTGDS or SOX9 alleviated Hrev107-mediated suppression of migration and invasion. These results suggest that Hrev107 will suppress cell migration/invasion through the PGD2 signaling pathway. In conclusion, Hrev107 can interact with PTGDS to enhance its function and to further suppress NT2/D1 cell migration and invasion.
Citation Format: Fu-Ming Tsai, Chang-Chieh Wu, Rong-Yaun Shyu, Shun-Yuan Jiang. Hrev107 enhances prostaglandin D2 synthase-mediated cancer cells suppression in the testis. [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 5384. doi:10.1158/1538-7445.AM2013-5384
Abstract 5390: Chemical disruption of Wnt protein fatty acylation as an anti-cancer therapeutic strategy.
Authors: Tuladhar Rubina , Lum Lawrence 
Published: August 2014

Abstract
The secreted Wnt signaling molecules are associated with a broad range of cancers and represent high priority therapeutic targets. Recently identified small molecules that disrupt Wnt biosynthesis by disabling the extracellular acyltransferase Porcupine (Porcn) form the basis of a novel targeted anti-cancer therapeutic strategy. Porcn is a founding member of a sixteen gene family known as Membrane-Bound O-Acyltransferases (MBOATs) that likely control the production of a broad range of disease-relevant signaling molecules. A deeper understanding of the chemical-protein interaction that confers Porcn inhibitors with selectivity would facilitate the engineering of improved Porcn inhibitors and molecules with activity against other MBOAT family members. Using synthetic fatty acyl analogues that allow direct labeling of Wnt proteins and chemical inhibitors of fatty acid metabolic enzymes, we have uncovered that Porcn utilizes a monounsaturated 16-carbon fatty acid as a substrate. Chemical disruption of stearoyl-CoA desturase (SCD) that converts palmitate to palmitoleate blocks Wnt protein production and activity thus revealing another potential chemical strategy for inhibiting Wnt-dependent cancerous growth. The inability of several other Porcn family members with known protein substrates to utilize palmitoleate may account for the selectivity of Porcn classes of inhibitors. Our study expands the number of drug targets to include those enzymes that control the production of secreted signaling molecules and reveals a direct influence of cellular metabolic status on coordinated and cancerous cell growth regulation.
Citation Format: Rubina Tuladhar, Lawrence Lum. Chemical disruption of Wnt protein fatty acylation as an anti-cancer therapeutic strategy. [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 5390. doi:10.1158/1538-7445.AM2013-5390
Abstract 5392: Metabolic profiling of castrate-resistant prostate cancer reveals novel role for bile acids in driving castration resistance.
Authors: Chakravarthy Divya , Rivas Paul , Keppler Brian , Ruan Jianhua , Ghosh Rita , Kumar Addanki Pratap 
Published: August 2014

Abstract
The 5-year survival for metastatic castrate-resistant prostate cancer patients is less than 30% despite significant progress in the understanding of prostate cancer biology and development of novel therapeutic agents. A major contributing factor for the observed low survival rate of patients with castrate resistant disease is the lack of knowledge regarding metabolic alterations and their underlying contributions during development of castrate-resistant phenotype. Studies conducted in our laboratory and others identified a potential role for 2-methoxyestradiol (2-ME2) to prevent prostate cancer development and progression through inhibition of the anti-apoptotic protein FLIP. The goal of the current study was to identify biochemical changes in response to castration and treatment with 2-ME2 in serum from transgenic adenocarcinoma of mouse prostate (TRAMP) mice using mass spectrometry based global profiling. We identified a total of 54 biochemicals of which 16 increased and 38 decreased in castrated animals compared to sham-castration. Treatment of sham-castrated animals with low and high doses of 2-ME2 altered 91 and 145 biochemicals respectively. On the other hand treatment of castrated animals modulated 89 and 106 biochemicals. Cumulative analysis of these data also identified alteration of 60 biochemicals associated with castration effect, 149 with treatment and 70 interactions between castration and treatment effects. Castration affected metabolites involved in variety of metabolic pathways including lipid, oxidative stress, energetics and bile acid. Given the data showing enhanced expression of FLIP in castrate-resistant prostate tumors and upregulation of bile acids in patients undergoing androgen deprivation therapy, we examined the activation of FLIP in prostate cancer cells in response to deoxycholic acid (DCA). Our data suggests that transcriptional activity of FLIP was higher in PC-3 cells treated with DCA. To the best of our knowledge, this is the first report demonstrating global metabolomic profiling of serum in response to castration and provide a framework for therapeutic targeting of bile acid metabolism. Supported by NIH CA 135451 (APK).
Citation Format: Divya Chakravarthy, Paul Rivas, Brian Keppler, Jianhua Ruan, Rita Ghosh, Addanki Pratap Kumar. Metabolic profiling of castrate-resistant prostate cancer reveals novel role for bile acids in driving castration resistance. [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 5392. doi:10.1158/1538-7445.AM2013-5392
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 5400: Exercise activates AMP-activated protein kinase in breast cancer cells.
Authors: Højfeldt Grith W. , Dethlefsen Christine , Pedersen Bente K. , Hojman Pernille 
Published: August 2014

Abstract
Objective: Cancer cells are characterized by a changed cellular metabolism, favoring glycolysis. AMPK, a serine/threonine kinase regulates cellular metabolism, and induces fatty acid oxidation and has in regard to this, been shown to suppress tumor cell growth. During physical activity, which is associated with a reduced cancer risk, working muscles secrete myokines, known to activate AMPK. This could indicate a connection between AMPK activity, myokine release from the working muscle, and an anti-cancer response. We hypothesize that exercise-induced myokine secretion causes an anti-cancer response via AMPK activation. Methods: Exercise-induced AMPK activation was studied in two models, 1) A cell study using the two breast cancer cell lines, MDA-MB-231 and MCF-7, incubated with exercise-conditioned serum, representing a myokine pool. Serum was collected from 9 females during a 2 hours cycling bout, and during a subsequent 3 hours rest. Following incubation, cell viability and AMPK phosphorylation was determined in the cells. 2) An In Vivo model, where the two cell lines were injected into nude mice. When the tumors reached 6 mm in diameter, the mice were subjected to 1 hour forced swimming bout, after which the tumors were dissected and analyzed for pAMPK content. Results: 1) Cell study: Two hours of cycling induced a 6-fold increase in serum IL-6, as expected. Incubating cancer cells with this post-exercise serum resulted in a significant reduction in the viability of MCF-7 cells, while no effect on the viability of MDA-MB-231 cells were observed. Preliminary data show increased AMPK phosphorylation in both MDA-MB-231 and MCF-7 cells after incubation with 5% exercise-conditioned serum. 2) In vivo study: 1 hour of swimming resulted in significantly increased AMPK phosphorylation in the MCF-7 tumors. Conclusion: Our preliminary data indicate that exercise-induced factors can cause decreased viability and increased AMPK activity in MCF-7 cells, while MDA-MB-231 cells need further investigation. Acknowledgement: The Centre of Inflammation and Metabolism (CIM) is supported by a grant from the Danish National research Foundation (#02-512-55). This study was further supported by the Danish Medical Research Council and the Lundbeck Foundation.
Citation Format: Grith W. Højfeldt, Christine Dethlefsen, Bente K. Pedersen, Pernille Hojman. Exercise activates AMP-activated protein kinase in breast 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 5400. doi:10.1158/1538-7445.AM2013-5400
Abstract 5402: Synergism of Metformin and DFMO on colon cancer proliferation and migration.
Authors: Zhang Yanping , Rodriguez Luz M. , Lubet Ronald , Hsueh Eddy C. 
Published: August 2014

Abstract
Introduction: Metformin has been shown to inhibit cancer cell growth via activation of MAP kinase with resultant inhibition of mTOR signaling pathway. ODC, a key enzyme in polyamine biosynthesis, was found to be overexpressed in colon cancer. We determined the effect of metformin in combination with DMFO, an ODC inhibitor, on tumor proliferation and migration in human colon cancer cells. Methods: Human colon cancer cells, HCT 116 and HT 29, were treated with Metformin, DFMO, or combination. Cell proliferation assay was performed using Cell Titer Blue proliferation assay. Cell migration assay was performed by seeding colon cancer cells in 24-well plate. After overnight incubation, an artificial homogenous wound was created onto the monolayer with a plastic micropipette tip. After wounding, the migration of cells into the wound was observed up to 72 hours at various time points. Quantitative RT-PCR for ODC1 detection was performed using Assay-on-Demand Hs00159739-ml. GAPDH served as control. Western blotting was performed to determine the expression of AMP kinase, mTOR, p70S6K and 4E-BP1. Data were presented as means ± SD for the three separate experiments. For comparison between groups, the student's t test was used and p&lt; 0.05 was considered to be statically significant. Results: There was dose-dependent (1-10 mM for DFMO and 1-20 mM for metformin) time-dependent (up to 96 hours) inhibition of cell proliferation and migration with either metformin or DFMO in both HCT 116 and HT 29 cells. Synergistic inhibition was observed with the combination treatment (5 mM DFMO and 5 mM Metformin) on both cell migration and proliferation at 24 hours compared with either agent alone. There was synergistic inhibition of ODC expression with the combined treatment compared with DFMO alone at 24 hours (p&lt;0.01). The combination treatment also lead to significant enhancement of AMPK activation and increased phosphorylation of AMPKα at Thr-172 compared with metformin alone (p&lt;0.01). The combination treatment resulted in significant inhibition of mTOR signaling with decreased phosphorylation of mTOR, p70S6K and 4E-BP1 in treated cancer cells, when compared with individual drug treatments. Inhibition of proliferation and migration was significantly greater in the mismatch-repair defective HCT 116 cells than HT 29. Conclusion: We have observed a synergistic effect of metformin and DFMO in suppressing human colon cancer proliferation and migration. The synergism reflects enhanced inhibition of both polyamine synthesis and mTOR signaling pathways by the drug combination.
Citation Format: Yanping Zhang, Luz M. Rodriguez, Ronald Lubet, Eddy C. Hsueh. Synergism of Metformin and DFMO on colon cancer proliferation and migration. [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 5402. doi:10.1158/1538-7445.AM2013-5402
Abstract 5405: Limiting glucose availability with metformin increased reactive oxygen species, decreased cell survival, and promoted apoptosis in human and mouse pancreatic cancer cells.
Authors: Yan Guang , Freeman Theresa , Lanza-Jacoby Susan 
Published: August 2014

Abstract
Background: Recently, we found that calorie restriction (CR) protected K-ras G12D; Pdx-1Cre mice against the progression of advanced PanIn lesions and pancreatic cancer. Since CR limits glucose availability, the CR mimetic metformin is also potential approach to prevent pancreatic cancer. Recent studies found that metformin reduced the incidence of pancreatic cancer in diabetic patients. However, it is not clear how metformin promotes the anticancer effects. One potential mechanism is by altering reactive oxygen species (ROS) and autophagy. In this in vitro study, we explore the role of ROS and autophagy in mediating the growth-inhibitory effects of metformin by treating pancreatic cancer cells and normal pancreatic ductal cells with metformin.
Methods: We acclimated MiaPaca and KP mouse pancreatic tumor cells from K-ras G12D; Pdx-1Cre mice to physiological concentrations of glucose and then treated cells cells with metformin with and without the antioxidant N-acetyl cysteine (NAC) or chloroquine (autophagy inhibitor) for 24h. Cell viability, ROS production, and apoptosis were measured.
Results: Metformin decreased viability of MiaPaca and KP cells in a concentration-dependent manner in comparison to untreated cells; metformin did not have any effect in HPNE human pancreatic normal epithelial cells. Pretreating MiaPaca and KP cells with NAC increase survival and decreased apoptosis, which suggests that ROS promotes the growth-inhibitory and apoptotic effect of metformin. Metformin increased ROS formation in MiaPaca and KP cells but not in HPNE cells. Cell survival increased and apoptosis decreased when MiaPaca cells were pretreated with chloroquine. Our findings suggest that ROS and autophagy may mediate the cytotoxic effects of metformin in MiaPaca and KP pancreatic cancer cells.
Conclusion: In summary, metformin may be a potential chemoprevention agent against pancreatic cancer without cytotoxic effects in normal pancreatic ductal cells.
Citation Format: Guang Yan, Theresa Freeman, Susan Lanza-Jacoby. Limiting glucose availability with metformin increased reactive oxygen species, decreased cell survival, and promoted apoptosis in human and mouse pancreatic 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 5405. doi:10.1158/1538-7445.AM2013-5405
Abstract 5416: Metabolic control of the prometastatic protein CD147.
Authors: Papathanassiu Adonia E. , Vu Hong A. 
Published: August 2014

Abstract
Apart from a recent report suggesting that hypoxia upregulates CD147, little is known about the mechanisms responsible of the tumoral overexpression of CD147, a transmembrane and secretory glycoprotein known to promote metastasis through multiple mechanisms. Here, we report that the total and surface concentration of CD147 appear to be under metabolic control. Glucose (Glc) deprivation in MDA-MB-231 and MDA-MB-435 tumor cells leads to a decrease in the levels of total CD147 and a dramatic increase in the expression of cell surface CD147. A similar mobilization of CD147 to the plasma membrane was observed with glutamine (Gln) deprivation in MDA-MB-435 cells; when the cells were deprived of both nutrients (Glc and Gln) a dramatic increase (∼6-fold) in the cell surface expression of CD147 was observed. Plasma membrane associated CD147 is known to promote metastasis through homotypic and heterotypic interactions between cancer and stromal cells. An 80% reduction in the membrane found CD147 was observed when Gln-deprived cells were treated with ERG-240, a small molecule that inhibits the cytosolic form of BCAT, the enzyme responsible for the reversible transamination of leucine (Leu). On the other hand, Leu deprivation was shown to decrease CD147 by 6-7 fold in both cancer cell lines tested here. Treatment of the cells with ERG-240 partially reversed the increase in the levels of CD147 seen after supplementation of the Leu-deprived cells with 105 mg/L Leu. CD147 is known to possess 3 N-glycosylation sites and to exist in forms with various degrees of glycosylation; the fully glycosylated protein is associated with an increased prometastatic potential. Inhibitors of N-glycosylation, such as 2-deoxyglucose (2DG), are known to possess anticancer properties. In the present study, treatment of MDA-MB-231 cells in vitro with 10 mM 2DG led to 80% reduction of the cell surface expression of highly glycosylated CD147 without the concomitant reduction in the total concentration of CD147. In contrast, treatment of athymic female nude mice, bearing orthotopically implanted MDA-MB-231 tumors, with 125 mg/Kg 2DG twice a week led to tumors that expressed markedly increased levels of the highly glycosylated CD147 variant (Control/Treated or T/C=2.3, p=0.01). The increased expression of the protein in the 2DG-treated tumors was accompanied with an increase in the levels of circulating human CD147 (T/C=1.7, p=0.01) normalized per tumor volume. Collectively, the data point towards a metabolic control of CD147 and suggest that inhibition of tumor growth due to nutrient deprivation may initiate pathways that promote metastasis.
Citation Format: Adonia E. Papathanassiu, Hong A. Vu. Metabolic control of the prometastatic protein CD147. [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 5416. doi:10.1158/1538-7445.AM2013-5416
Abstract 5417: HIF1α is a master regulator with the facilitate of demethylation for the hexokinase 2 expression during cancer progression.
Authors: Kim Hyemi , Lee Hyun G. , Lee Jae Myun , Park Jeon Han 
Published: August 2014

Abstract
Hexokinase 2 (HK2) is a key enzyme of aerobic glycolysis, known as the Warburg effect. A recent report showed that the HK2 expression in glioblastoma multiforme correlates with the progression of cancer and the survival of patients. The regulation of HK2 expression in cancer cells has been explored for many decades, however the precise mechanism is not yet identified. HK2 gene has a 4-kb promoter, which contains the potential responsive elements for glucose, insulin, glucagon, TPA, cAMP and HIF1 α. However, methylation of the promoter region makes normal cells nearly silent in HK2 expression. A study showed the potential contribution of demethylation of promoter for the HK2 expression during cancer progression.
In this study, we tried to identify the master regulator of HK2 expression. We performed methylation beadchip array for the comparison of methylation status of HK2 gene between normal tissues and hepatocellular carcinoma (HCC). The 5’-UTR and 3’-UTR are densely methylated in normal tissues, but significantly demethylated in HCC. Moreover, we identified new hypoxia responsive element (HRE) through the deletion and site-directed mutagenesis study with 2-kb promoter of human HK2. The mutation of new HRE diminished the luciferase activity. Specific interaction between HIF1 α and HRE were identified by ChIP and EMSA. Then, we showed that demethylation by 5-Aza-deoxycytidine could contribute to the HK2 expression in hypoxic condition.
In conclusion, we revealed the mechanism of HK2 expression and hypoxia is one of the major regulator among pre-known regulators. The sequential events, demethylation and exposure to hypoxic environments are the main requisite for the HK2 expression during the cancer progression.
Citation Format: Hyemi Kim, Hyun G. Lee, Jae Myun Lee, Jeon Han Park. HIF1α is a master regulator with the facilitate of demethylation for the hexokinase 2 expression during cancer progression. [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 5417. doi:10.1158/1538-7445.AM2013-5417