bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2177: Differential expression of stromal cell-related genes between primary nasopharyngeal carcinoma and distant metastasis
Authors: Ke Liangru , Chen Jinna , Wang Lin , Yu Yahui , Ye Yanfang , Xia Weixiong , Lv Xing , Yang Jing , Guo Xiang , Xiang Yanqun , Guan Xinyuan 
Published: August 2015

Abstract
Stromal cells in the tumor microenviroment play an important role in development and progression of nasopharyngeal carcinoma (NPC). Aim of this study is to identify the stromal cell related genes which may promote distant metastasis in NPC. Materials and methods: Differently expressed genes were accessed by comparing nasopharyngeal carcinoma and distant metastasis by microarray. Then stromal cells related genes were analyzed by using statistics tools. Five selected genes were validated in 112 nasopharyngeal carcinoma specimens. Results: We have identified 3360 genes up-regulated (P &lt; .05)and 2327 genes down-regulated(P &lt; .05) in distant metastasis versus primary nasopharyngeal carcinoma, among the differently expressed genes,111 stromal cells related genes were picked up according to previous researches for cluster analysis and pathway analysis. Upon validating 5 selected genes (BIRC3,FRAS1,NPNT,POSTN,PCSK6) in 112 additional NPC cases, the authors found that expression of POSTN was negative correlated significantly with lymph node involvement (p = 0.006)and clinical stage(p = 0.035) at the moment of diagnosis and FRAS1 was negative correlated with disease-free survival (p = 0.002) and distant metastasis survival (p = 0.02).Conclusion: Increasing knowledge of metastasis promotion of stromal cells related genes may provide feasible explanations underlying NPC progression and metastasis along with the development of biomarkers for screening high-risk populations.
Citation Format: Liangru Ke, Jinna Chen, Lin Wang, Yahui Yu, Yanfang Ye, Weixiong Xia, Xing Lv, Jing Yang, Xiang Guo, Yanqun Xiang, Xinyuan Guan. Differential expression of stromal cell-related genes between primary nasopharyngeal carcinoma and distant metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2177. doi:10.1158/1538-7445.AM2015-2177
Abstract 2188: Different gene expression between men and women patients with lung adenoarcinoma reveals enrichment of immune gene sets
Authors: Pinto Joseph A. , Araujo Jhajaira M. , Prado Alexandra , Flores Claudio , Cardenas Nadezhda K. , Zaharia Mayer , Sarria Gustavo , Aguilar Alfredo , Neciosup Silvia , Gomez Henry , Mas Luis 
Published: August 2015

Abstract
INTRODUCTION:
There is different susceptibility to DNA damage induced by tobacco smoking between women and men. In despite of the great advances in the knowledge of the genomic landscape of lung cancer, is not explored the molecular differences between man and women. Our aim was to evaluate differentially enriched gene sets between the two genders.
METHODS:
We evaluated 03 public databases containing gene expression values from lung adenocarcinoma patients: GSE50081 (HG-U133_Plus_2; n = 181 samples), GSE47115 (Illumina HumanHT-12 WG-DASL V4.0 R2; n = 46 samples), GSE10072 (HG-U133A; n = 107 samples). We perform the Gene Set Enrichment Analysis (GSEA) to find differences between the genders. Each dataset was analyzed individually and was divided in cohorts of smokers and non-smokers (and healthy tissues by smoking status when it was included in the dataset). Cases with unknown smoking status and former smokers were excluded from the analysis. We use the Gene Ontology biological process terms to find similar enriched pathways between cohorts. We consider enriched process with statistical differences (p&lt;0.05) or trends (P&lt;0.08) in at least a cohort.
RESULTS:
The analysis did show immune genes enrichment in women such as cytokine production, defense response to bacteria and response to other organisms. In another hand, regulation of JNK and MAPKKK cascades was enriched in tumors and healthy tissues from non-smokers women. In men, the oxidoreductase activity acting on sulfur group of donors was enriched in smoking men.
CONCLUSION:
There are differences between tumors from women and men that should be deeply explored.
Citation Format: Joseph A. Pinto, Jhajaira M. Araujo, Alexandra Prado, Claudio Flores, Nadezhda K. Cardenas, Mayer Zaharia, Gustavo Sarria, Alfredo Aguilar, Silvia Neciosup, Henry Gomez, Luis Mas. Different gene expression between men and women patients with lung adenoarcinoma reveals enrichment of immune gene sets. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2188. doi:10.1158/1538-7445.AM2015-2188
Abstract 2190: Oncostatin M reduces SLUG expression in lung adenocarcinoma cells through STAT1-PIAS4-dependent histone deacetylation
Authors: Pan Chih-Ming , Wang Mong-Lien , Wu Cheng-Wen 
Published: August 2015

Abstract
We previously described that mesenchymal stem cells (MSCs) secrete a multifunctional cytokine - Oncostatin M (OSM) which effectively inhibited the metastasis and growth of LAC cells, and reduce the SLUG expression, leading to mesenchymal-epithelial transition (MET). Our data showed that the OSM-dependent inhibition of SLUG is mediated by a STAT1-dependent pathway through a transcriptional control. Previous studies have shown both positive and negative role of STAT1 in transcriptional regulation of its downstream target genes. However, the underlying mechanism of how STAT1 mediates the suppression of SLUG transcription remains elusive.
To investigate the associated effector or mediator in OSM-induced STAT1-dependent SLUG suppression, we knocked down PIAS4 (PIAS4-KD), a co-repressor of STAT1, in A549 cells using lentiviral expressed short hairpin RNAs (shRNA). We demonstrated that knockdown of PIAS4 reversed the OSM-suppressed SLUG level and resulted in a higher SLUG mRNA in comparison to scrambled shRNA control. Moreover, we constructed SLUG promoter-driven luciferase expression reporters and test the effect of PIAS4 on SLUG promoter activity. We observed that PIAS4-KD cells expressed higher SLUG promoter activity than control cells, and OSM treatment further augmented this difference. In contrast, reconstitution of PIAS4 expression in PIAS4-KD cells decreased the SLUG promoter activity. Chromatin immuneprecipitation assay (ChIP) revealed the binding of PIAS4 to SLUG promoter region one hour after OSM administration. We also showed OSM-induced tyrosine-phosphorylated STAT1 interacts with PIAS4 and HDAC1 in a co-immunoprecipitation assay. Finally, the level of H3K9 acetylation in SLUG promoter region decreased significantly upon OSM treatment, and the pan HDAC inhibitor, trichostatin A (TSA) rescues OSM-induced suppression of SLUG promoter activity.
Our findings demonstrated the underlying mechanism of the tumor-suppressive effect of OSM, and revealed a STAT1-PIAS4-dependent regulation of SLUG promoter through histone deacetylation.
Citation Format: Chih-Ming Pan, Mong-Lien Wang, Cheng-Wen Wu. Oncostatin M reduces SLUG expression in lung adenocarcinoma cells through STAT1-PIAS4-dependent histone deacetylation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2190. doi:10.1158/1538-7445.AM2015-2190
Abstract 2192: Stress-induced reprogramming of epithelial cancers toward a stem-like fate
Authors: Gozo Maricel C. , Cheresh David A. , Yebra Mayra , Sequin Laetitia 
Published: August 2015

Abstract
Cancer cell plasticity has become a focus of intense study as it impacts both therapy and drug resistance. Epigenetic changes contributing to cellular plasticity and stemness allow tumor cells to adapt to microenvironmental stress and or drug treatment. We recently reported that the heterodimer integrin receptor αvβ3 serves as a marker of stem-like breast, lung, and pancreatic carcinomas that are highly resistant to receptor tyrosine kinase inhibitors such as erlotinib. In fact, αvβ3 was found to be both necessary and sufficient to drive stemness, drug resistance, and tumor progression. Here, we report that β3 expression is expressed in response to a range of cellular stresses, including nutrient deprivation, hypoxia, oxidative stress, and cancer therapy. Stress-induced β3 gene expression is enhanced by epigenetic histone modifications that promote an open chromatin state enabling binding of the HNF4A transcription factor to the β3 promoter. Once expressed, β3 induces reprogramming toward a stem-like fate by driving a subset of NFκB target genes, including FOXP1, a transcription factor that controls expression of pluripotency genes OCT4 and NANOG. Therefore, stress-induced chromatin remodeling and the HNF4A-mediated induction of β3 expression triggers a switch from an epithelial to a cancer stem-like phenotype. Evidence is provided that pharmacological blockade of this epigenetic change not only inhibits β3 expression but reverses tumor stem-like properties and enhances their response to therapeutic standard of care. These findings define a stress-induced but reversible epigenetic pathway leading to β3 expression on a range of epithelial cancers that drives cancer stemness, tumor progression and drug resistance.
Citation Format: Maricel C. Gozo, David A. Cheresh, Mayra Yebra, Laetitia Sequin. Stress-induced reprogramming of epithelial cancers toward a stem-like fate. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2192. doi:10.1158/1538-7445.AM2015-2192
Abstract 2193: Hypoxia-induced G9a histone methyltransferase is crucial for blunting RUNX3 tumor suppressor function
Authors: Lee You Mie 
Published: August 2015

Abstract
Recent our work shed light on the critical roles of RUNX3 in early tumorigenesis. Hypoxia has been reported to be an early tumorigenic insult. Previously, we showed that RUNX3 is silenced by G9a HMT under hypoxia. However, the possible direct modification of RUNX3 by G9a induced by hypoxia and its outcome are not yet investigated. Here we show that RUNX3 physically interacts with G9a. Under hypoxic conditions, G9a directly methylates lysines 129 and 171 of RUNX3. G9a-methylated RUNX3 is localized to the cytoplasm and degrade through Smurf-mediated ubiquitination pathway. Hypoxia and G9a overexpression decreased RUNX3-responsive genes by DNA microarray analysis. Consistently, tumor suppressive role of RUNX3 was decreased by G9a-mediated methylation in gastric cancer xenograft model. Taken together, our results demonstrate that methylation by G9a is a key chemical modification for the regulation of RUNX3 tumor suppressor function in hypoxic conditions and in early tumorigenic stage.
Citation Format: You Mie Lee. Hypoxia-induced G9a histone methyltransferase is crucial for blunting RUNX3 tumor suppressor function. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2193. doi:10.1158/1538-7445.AM2015-2193
Abstract 2201: EGFR regulates the expression and activity of ARID3B through phosphoinositide 3-kinase
Authors: Hallas William M. , Cowden Dahl Karen 
Published: August 2015

Abstract
ARID3B is a transcription factor that is upregulated in ovarian cancer and its expression correlates with relapse following chemotherapy. However, the mechanism that leads to ARID3B's elevated expression in ovarian cancer has not been elucidated. EGFR is commonly overexpressed in ovarian cancer, as is phosphoinositide 3-kinase (PI3K), lending us to believe that this pathway may be regulating ARID3B. We demonstrated that epidermal growth factor receptor (EGFR) signaling induces expression of ARID3B through the ETS family transcription factor PEA3. However, the exact mechanism that controls EGFR induction of ARID3B has not been elucidated, and the impact of EGFR on ARID3B activity is unknown. To find the optimal time point for EGF induction of ARID3B mRNA, ovarian cancer cells were serum-starved and then treated with EGF for different amounts of time. We then examined the expression of ARID3B mRNA induced by this treatment in each case. We found that ARID3B was most strongly induced between 2 and 4 hours after treatment with EGF. We then performed dose curve experiments for the PI3K inhibitors, wortmannin and LY294002. We performed qRT-PCR to examine ARID3B mRNA expression under the different concentrations of inhibitors. Western blots for the presence of phosphorylated Akt under each concentration demonstrated the effectiveness of the inhibitors. Next, ovarian cancer cells were serum-starved and then treated with EGF or EGF in combination with PI3K inhibitors. Both immunoprecipitation and chromatin immunoprecipitation (ChIP) were performed on these samples. Western blot for phospho-serine was conducted on immunoprecipitated samples to test for serine phosphorylation of ARID3B in response to growth factor signaling. We found that ARID3B is serine phosphorylated. Next, we performed ChIP to assess the binding of ARID3B to select target genes. We found on the genes we tested, EGF treatment decreased DNA promoter binding. Binding was greatest in the serum-starved samples and the samples treated with the PI3K inhibitors. Very little binding was seen in the EGF treated cells. These results were consistent for a number of ARID3B target genes. In future studies, we will determine which serine residues are phosphorylated by doing a mass spectrometric analysis. Then, site directed mutagenesis will be conducted to test the requirement of serine phosphorylation to target gene regulation. By understanding how ARID3B functions as a transcription factor, we will gain critical insight into ovarian cancer relapse and progression.
Citation Format: William M. Hallas, Karen Cowden Dahl. EGFR regulates the expression and activity of ARID3B through phosphoinositide 3-kinase. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2201. doi:10.1158/1538-7445.AM2015-2201
Abstract 2202: Novel regulation of pro-migratory genes by nuclear Src in pancreatic cancer cells
Authors: Paladino David 
Published: August 2015

Abstract
Pancreatic cancer is an exceptionally lethal malignancy with a poor prognosis, and there is little known about the molecular mechanisms that lead to the disease and its progression. Several reports have implicated dysregulated Src tyrosine kinase function in pancreatic tumorigenesis and progression. However, except for the classic role of Src in promoting events that contribute to invasiveness, not much is known of how the tyrosine kinase supports pancreatic cancer progression and the poor response of the disease to therapy. In previous reports, we showed that Src is present in the cell nucleus of pancreatic cancer cells in association with gene promoter sequences. Mass spectrometry analysis of Src co-immune complex from nuclear lysate preparations from pancreatic cancer cells identified p300 as a novel Src-interacting protein. Chromatin immunoprecipitation coupled to human promoter microarray (ChIP-chip) analysis showed that nuclear Src is associated with the promoters of SMYD3 and HMGA2 in pancreatic cancer cells. Inhibition of Src tyrosine kinase or p300 lysine acetyltransferase activity decreased the expression of SMYD3 and HMGA2 mRNA and protein levels in pancreatic cancer cells in a time-dependent manner and blocked pancreatic cancer cell migration. Current data altogether show that Src at the inner nuclear envelope is physically associated with and regulates the expression of SMYD3 and HMGA2, through interaction with p300. The studies identify a novel Src function through epigenetic regulation of pro-metastatic genes and provide additional potential avenues for developing new treatment strategies for metastatic pancreatic cancer.
Citation Format: David Paladino. Novel regulation of pro-migratory genes by nuclear Src in pancreatic cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2202. doi:10.1158/1538-7445.AM2015-2202
Abstract 2224: Functional role of NRF2 signaling in sphere cultured carcinoma cells
Authors: Ryoo In-geun , Kwak Mi-Kyoung 
Published: August 2015

Abstract
Cancer stem cells (CSCs) are known to express high levels of antioxidant proteins and ABC transporters. In this study, we investigated the potential involvement of NF-E2-related factor 2 (NRF2) in CSC survival and stress response by using the MCF7 mammosphere culture, which is accepted as a CSCs-enriched system. The levels of NRF2 protein, reporter transcription activity, and target gene expression such as efflux transporters were higher in mammospheres than in the monolayer. We observed that proteasome activity as well as catalytic subunits expression was decreased in the mammospheres. Additionally, mammospheres showed an elevated p62 protein level and p62-knockdown suppressed NRF2 activation. The role of NRF2 in mammospheres could be demonstrated in NRF2-knockdown mammospheres. Sphere growth was retarded in knockdown group and anticancer drugs resistance was not obtained in NRF2-knockdown mammospheres in contrast to the control mammospheres. NRF2 activation could be confirmed in spheres-culture of colon cancer and ovarian cancer cells. These results show that reduced proteasome function and elevated p62 level contributed to NRF2 activation in CSCs-enriched mammospheres. The study further suggests a potential role of NRF2 in CSCs survival and stress resistance.
Citation Format: In-geun Ryoo, Mi-Kyoung Kwak. Functional role of NRF2 signaling in sphere cultured carcinoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2224. doi:10.1158/1538-7445.AM2015-2224
Abstract 2226: PLSCR1- a modifier of TGFβ signaling
Authors: Klauzinska Margaret , Karasawa Hideaki , Rangel Maria Cristina , Castro Nadia , Baker Alyson , Bertolette Daniel , Krask Julie , Salomon David 
Published: August 2015

Abstract
The PLSCR family has been proposed to play a role in the redistribution of plasma membrane phospholipids. Recent work on the PLSCRs has revealed their additional functions such as signal transduction and lipid metabolism. The most studied member of this family, PLSCR1, has been shown to partition into lipid rafts implicating it in the regulation and endocytic trafficking of receptor-signaling complexes, e.g. EGFR. Additionally, PLSCR1 has been implicated in tumorigenesis although the exact mechanism of PLSCR1 is still controversial.
In a previous study, we identified PLSCRs, as novel Cripto-1 (CR-1) binding proteins that might modulate CR-1-dependent signaling pathways. In this study, we confirmed that PLSCR1 and PLSCR3 bind to Cripto-1 but also that PLSCR1 also inhibits TGFβ signaling via binding to the receptor complexes for the TGFβ superfamily. We also showed that PLSCR1 mediates protein degradation of type I receptors: Alk4 and TGFβRI but not ActRBII, TGFBRII or BMPRb.
Additionally, we demonstrated that PLSCR1 is overexpressed in human breast cancer tissue and in human breast cancer cell lines especially in triple-negative MDA-MB-231 and MDA-MB-468. We also showed that knockout of PLSCR1 inhibits migration, invasion and anchorage independent growth of MDA-MB-231, and that TGFβ influences PLSCR1 cellular distribution in those cells.
Citation Format: Margaret Klauzinska, Hideaki Karasawa, Maria Cristina Rangel, Nadia Castro, Alyson Baker, Daniel Bertolette, Julie Krask, David Salomon. PLSCR1- a modifier of TGFβ signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2226. doi:10.1158/1538-7445.AM2015-2226
Abstract 2231: Type II transglutaminase is an epidermal squamous cell carcinoma stem cell survival protein
Authors: Fisher Matt , Xu Wen , Adhikary Gautam , Kerr Candace , Eckert Richard 
Published: August 2015

Abstract
Cancer stem cells are thought to be responsible for rapid tumor growth, metastasis and enhanced tumor survival following drug treatment. For this reason, there is a major emphasis on identifying proteins that can be targeted to kill cancer stem cells or control their growth. Our studies suggest that transglutaminase type II (TG2) is such a target in epidermal squamous cell carcinoma. TG2 was originally described as a transamidase that catalyzes formation of ϵ-(γ-glutamyl)lysine bonds. However, subsequent studies reveal that TG2 is a GTP binding protein that plays an important role in cell signaling and survival. In the present study we show that TG2 is a target for anti-stem cell therapy in human squamous cell carcinoma. We identify TG2 as highly elevated in epidermal cancer stem cells (ECS cells) and show that TG2 knockdown or suppression of TG2 function with inhibitors reduces ECS cell survival, spheroid formation, matrigel invasion and migration. The reduction in survival is associated with activation of apoptosis. Mechanistic studies, using TG2 mutants suggest that the GTP-binding activity is required for maintenance of ECS cell growth and survival. These studies suggest that TG2 has an important role in maintaining cancer stem cell survival, invasive and metastatic behavior, and is an important therapeutic target to reduce survival of cancer stem cells in epidermal squamous cell carcinoma.
Citation Format: Matt Fisher, Wen Xu, Gautam Adhikary, Candace Kerr, Richard Eckert. Type II transglutaminase is an epidermal squamous cell carcinoma stem cell survival protein. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2231. doi:10.1158/1538-7445.AM2015-2231