bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 497: Hypoxic stress enhances tumorigenic potential of PPARδ in colon cancer cells
Authors: Lee Joo Young , Jeong Eunshil , Koo Jung Eun , Yeon Sang Hyun 
Published: May 2015

Abstract
Peroxisome proliferator-activated receptor (PPAR) δ is reported to be deeply implicated in the process of colon carcinogenesis. However, the crosstalk between PPARδ in colon cancer cells and a hypoxic tumor microenvironment is not entirely understood. Hypoxia (&lt;1% O2) and deferoxamine (a hypoxia mimetic) induced the expression of tumor-promoting cytokines, IL-8 and VEGF, in colon cancer cells (HCT116). In contrast, the induction of IL-8 and VEGF by hypoxic stress was greatly attenuated in PPARδ-knockout HCT116 cells. Consistently, while HCT116 cells stimulated with hypoxic stress were able to promote the vascular formation of endothelial cells and the migration of macrophages, the capacity of PPARδ-knockout HCT116 cells to induce angiogenesis and macrophage activation was greatly attenuated. Hypoxic stress enhanced DNA binding activity of PPARδ in HCT116 cells showing PPARδ transactivation was stimulated by hypoxic stress. Overexpression of p300 enhanced deferoxamine-induced transcriptional activation of PPARδ whereas siRNA knockdown of p300 decreased deferoxamine-induced PPARδ transactivation. Inhibition of PI3K/Akt pathway by LY294002 or siRNA-Akt resulted in the decrease of PPARδ transactivation induced by hypoxia and deferoxamine in HCT116 cells. Collectively, the results show that PPARδ plays a role in hypoxic stress-induced cytokine expression in colon cancer cells, leading to the promotion of angiogenesis and macrophage activation in the tumor microenvironment. p300 and the PI3K/Akt pathway participate in the regulation of hypoxic stress-mediated PPARδ transactivation in colon cancer cells. Our results suggest that the positive crosstalk between PPARδ in colon cancer cells and hypoxia in tumor microenvironment aggravate and accelerate the progress of tumorigenesis.
Citation Format: Joo Young Lee, Eunshil Jeong, Jung Eun Koo, Sang Hyun Yeon. Hypoxic stress enhances tumorigenic potential of PPARδ in colon cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 497. doi:10.1158/1538-7445.AM2014-497
Abstract 4970: The role of POU5F1B in prostate cancer
Authors: Jiang Hongmei , Wang Man-Tzu , Nie Daotai 
Published: May 2015

Abstract
POU5F1B is the one of the pseudogenes of POU5F1 (also known as Oct3, Oct4) with protein-coding potential. It is localized on chromosome 8q24.21, inside of the 1.2 Mb “gene desert” between the FAM84B and the c-MYC gene, which is closely associated with prostate cancer risk. Recent studies shown that POU5F1B, but not POU5F1, is expressed in prostate tissue and is overexpressed in prostatic carcinoma, compared to normal prostatic tissue surrounding the carcinoma. However, the role of POU5F1B in prostate cancer is still unknown. Through in silico analysis of dataset HG-U95A, we found that POU5F1B expression is increased in prostate tumor and markedly increased in metastatic tumors. Western blot analysis revealed a marked increase in POU5F1B expression in prostate cancer cells when compared to non-tumorigenic RWPE-1 cells. To study the role of POU5F1B in prostate cancer, we cloned POU5F1B from prostate cancer cells, sequenced the amplicons, and found several polymorphism. We made pCDH-myc-POU5F1B constructs and expressed POU5F1B in prostate cancer cell lines LNCaP, DU145, and PC-3. Prostate cancer cell lines that ectopically overexpress POU5F1B form dramatically fewer cell-cell junctions and exhibit significantly increased invasiveness in vitro. Further, we found that E-Cadherin expression is downregulated in DU145-POU5F1B cells. Methylation of the E- Cadherin locus is increased in DU145-POU5F1B cells and methyltransferase inhibitors can partially restore E-Cadherin expression. These data collectively suggest an important role of POU5F1B in prostate tumor progression and metastasis.
Citation Format: Hongmei Jiang, Man-Tzu Wang, Daotai Nie. The role of POU5F1B in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4970. doi:10.1158/1538-7445.AM2014-4970
Abstract 4973: Long non-coding RNA promotes metastatic behavior in Ewing sarcoma
Authors: Mitra Sheetal A. , Mitra Anirban P. , Buckley Jonathan D. , May William A. , Kapranov Philipp , Arceci Robert J. , Triche Timothy J. 
Published: May 2015

Abstract
Ewing sarcoma (ES) is a highly malignant bone and soft tissue tumor with a 20% 5-year survival rate for patients with metastatic disease. Further, even clinically localized tumors are not successfully treated with local therapy like surgery and radiation, indicative of sub-clinical dissemination at presentation, as noted by James Ewing in his original papers. Extensive research has led to better understanding of the molecular pathogenesis of the disease but few discoveries have been successfully translated into improving treatment of ES patients. Our aim is to identify and characterize novel genomic features that can be developed into therapeutic targets for metastatic ES. This study documents the importance of one such ES-specific long non-coding RNA (lncRNA) in invasion and metastasis.
Expression data from over a hundred ES primary tumors were compared to normal adult tissues as well as other types of pediatric and adult cancers to identify ES-specific coding and non-coding RNA transcripts. One highly expressed lncRNA, AK057037, was exclusively associated with ES. Further characterization of the transcript using loss of function studies showed that this 2.6 kb, 7 exon, polyadenylated RNA was directly regulated by EWS-FLI1, the chimeric oncoprotein that is the hallmark of ES and a major driver of tumorigenesis. In vitro, knockdown of the lncRNA resulted in reduced invasiveness of ES cells. In vivo, cells over-expressing the transcript showed statistically significant increase in metastasis compared to controls. Downstream targets included cell adhesion molecules such as cadherins and extracellular matrix proteins. Immunoprecipitation (IP) showed binding of the lncRNA to its direct targets. Binding of the lncRNA to other regulatory proteins also affected more global changes including promoter methylation and subsequent modulation of the downstream targets.
We conclude that this lncRNA is a highly specific and unique ES biomarker. It acts as an oncogene by promoting invasion and metastasis of ES cells by controlling expression of genes involved in these pathways. Understanding this additional regulation by non-coding RNAs will enable development of multi-modal therapies that may prove to be more effective in treating aggressive disease.
Citation Format: Sheetal A. Mitra, Anirban P. Mitra, Jonathan D. Buckley, William A. May, Philipp Kapranov, Robert J. Arceci, Timothy J. Triche. Long non-coding RNA promotes metastatic behavior in Ewing sarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4973. doi:10.1158/1538-7445.AM2014-4973
Abstract 4985: Cellular dormancy in residual disease following oncogene inhibition
Authors: Ruth Jason , Pant Dhruv , Keister Blaine , Sterner Christopher , Chodosh Lewis 
Published: May 2015

Abstract
Tumor recurrence is the primary cause of cancer-related mortality. Recurrent tumors arise from residual cancer cells surviving treatment of the primary tumor. It remains unclear whether residual tumor cells are quiescent, or whether they are proliferative but tumor recurrence is limited by a countervailing level of cell death, due to insufficient vascularization or an inhospitable microenvironment. Using inducible models for HER2/neu and Wnt1 mammary tumorigenesis, we found that residual tumor cells surviving oncogene inhibition are quiescent, and reside in a desmoplastic and well-vascularized microenvironment. We confirmed these results by performing gene expression analysis on residual tumor cells, primary tumor cells, recurrent tumor cells, and stromal cells. Gene ontology analysis identified dramatic downregulation of gene clusters associated with proliferation in dormant residual tumor cells compared to all other cell types. Genes we identified as up- or downregulated in dormant residual disease were identified in other models of dormancy, suggesting generalizable mechanisms underpinning dormancy in different contexts. Dormancy-specific changes in additional genes further suggest a role for both EMT and stem cell-related signaling in dormant residual disease which survives targeted therapy. Finally, we demonstrated quiescent residual disease in a xenograft model of breast cancer treated with clinically relevant targeted therapies. In summation, these results suggest both that residual disease may exhibit cellular dormancy following targeted therapy, and that some mechanisms regulating cellular quiescence may be similar across different contexts.
Citation Format: Jason Ruth, Dhruv Pant, Blaine Keister, Christopher Sterner, Lewis Chodosh. Cellular dormancy in residual disease following oncogene inhibition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4985. doi:10.1158/1538-7445.AM2014-4985
Abstract 499: RUNX2 protects human neuroblastoma cells against apoptosis
Authors: Gnanamony Manu , Mohanam Indra , Mohanam Sanjeeva 
Published: May 2015

Abstract
Neuroblastoma is the most common extracranial pediatric solid tumor with an undifferentiated status and is characterized by heterogeneous clinical courses. The RUNX gene family comprises RUNX1, RUNX2, and RUNX3 transcription factors and is closely involved in a variety of cellular processes including development, differentiation, and tumorigenesis. Since RUNX genes play crucial roles in neuronal differentiation, we studied the expression of RUNX mRNAs in human neuroblastoma NB1691 cells. An increased RUNX2 mRNA expression was found in NB1691 cells compared with RUNX1 and RUNX3 mRNAs. Hypoxia is known to be a significant physiological stress in the tumor microenvironment and is associated with tumor malignant phenotype. NB1691 cells exhibited an increased expression of RUNX2 mRNA upon exposure to hypoxia compared with normoxic cells. Knockdown of HIF-2α, but not HIF-1α, decreased hypoxia-induced up regulation of RUNX2 mRNA in NB1691 cells. BothHIF-1α and HIF-2α mRNAs as well as proteins were downregulated in hypoxic NB1691 cells treated with RUNX2 siRNA compared with non-targeted control siRNA. GLUT1, a HIF-1α downstream target gene and Oct4, a HIF-2α downstream target gene were also found to be decreased in RUNX2 siRNA-treated NB1691 cells exposed to hypoxia. Runx2 knockdown using RNA interference in NB1691 cells resulted in decreased cell proliferation under normoxic as well as hypoxic conditions. An increased percentage of apoptotic cells was found in NB1691 cells treated with RUNX2 siRNA, and this percentage further increased in hypoxic NB1691 cells treated with RUNX2 siRNA. Further, these observations were validated by TUNEL assay. Real-time PCR analysis revealed elevated levels of Bax, Puma, Noxa and Nix in NB1691 cells treated with RUNX2 siRNA compared with cells treated with non-targeted control siRNA-treated cells under hypoxic conditions. In conclusion, our study suggests that hypoxia up regulates RUNX2 in NB1691 cells in a HIF2α- dependent manner and RUNX2 protects neuroblastoma cells against apoptosis.
Citation Format: Manu Gnanamony, Indra Mohanam, Sanjeeva Mohanam. RUNX2 protects human neuroblastoma cells against apoptosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 499. doi:10.1158/1538-7445.AM2014-499
Abstract 5000: Upregulation of WDR26 promotes breast cancer cell growth, migration and invasion via enhancing PI3K/AKT signaling
Authors: Ye Yuanchao , Chen Songhai 
Published: May 2015

Abstract
Background: The phosphatidylinositol 3-kinase (PI3K) pathway is one of the most deregulated pathways in breast cancer. One of PI3K isoforms, p110 β, has been shown to be activated predominantly by G protein-coupled receptors (GPCRs) through the heterotrimeric G protein βγ subunits (Gβγ), and plays a key role in breast cancer development. PI3Ks mediates their effects primarily through the activation of select AKT, which consists of three isoforms. We have recently made important observations that diverse GPCRs converge at Gβγ to promote breast tumor cell growth and migration both in vitro and in vivo, and that a novel Gβγ-interacting protein, WDR26, promotes Gβγ-dependent signal transductions, including PI3K/AKT activation. In this study, we have evaluated the role of WDR26 in regulating PI3K/AKT signaling for breast tumor cell growth, migration and invasion.
Methods: The level of WDR26 expression was evaluated in breast cancer cells and human breast cancer samples by Western blotting and immunohistochemistry analysis. WDR26 was then downregulated by siRNAs or overexpressed in breast cancer cells, and the effects on PI3K/AKT activation, tumor cell proliferation, migration and invasion were evaluated in vitro.
Results: WDR26 was upregulated in a subset of highly malignant and invasive breast tumor cell lines (such as MDA-MB231 and DU4475), and high grade human breast tumor samples. Upon GPCR stimulation of breast tumor cells, WDR26 facilitated the formation of a signaling complex consisting of Gβγ, PI3Kβ and AKT2. Downregulation of WDR26 in MDA-MB231 and DU4475 cells using RNA interference inhibited PI3K/AKT activation, tumor cell growth, migration and invasion. Similar effects were achieved by disruption of WDR26 function through induced expression of WDR26 deletion mutants in MDA-MB231 cells. Conversely, overexpression of WDR26 in MCF7 cells enhanced PI3K/AKT activation and rendered MCF7 cell migration and enhanced proliferation.
Conclusions: Together, these results indicate that WDR26 serves as a scaffold to foster interactions between Gβγ, PI3Kβ and AKT2, thereby promoting Gβγ-dependent PI3K/AKT activation, thereby regulating breast tumor progression. WDR26, thus, may represent a novel target for the intervention of breast tumors.
Note: This abstract was not presented at the meeting.
Citation Format: Yuanchao Ye, Songhai Chen. Upregulation of WDR26 promotes breast cancer cell growth, migration and invasion via enhancing PI3K/AKT signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5000. doi:10.1158/1538-7445.AM2014-5000
Abstract 5001: GATA3 abrogates TGFbeta-mediated breast cancer invasion and metastasis
Authors: Sun Jianwei , He Huifang , Pillai Smitha , Chellappan Srikumar , Yang Shengyu 
Published: May 2015

Abstract
Transforming growth factor β (TGFβ) is a potent and context dependent regulator of tumor progression. TGFβ promotes the lung metastasis of basal-like (but not the luminal-like) breast cancer. Here, we demonstrated that fascin, a pro-metastasis actin bundling protein, was a direct target of the canonical TGFβ-Smad4 signaling pathway in basal-like breast cancer cells. TGFβ and Smad4 induced fascin overexpression by directly binding to a Smad binding element on the fascin promoter. Through data mining, we identified GATA3, a transcription factor crucial for mammary gland morphogenesis and luminal differentiation, as a potential regulator of fascin overexpression. When ectopically expressed in basal-like breast cancer cells, GATA-3 abrogated Smad4-mediated overexpression of fascin and other TGFβ response genes, invadopodium formation, cell migration and invasion, suggesting suppression of the canonical TGFβ-Smad4 signaling axis. Mechanistically, GATA3 might abrogate TGFβ and Smad4-mediated fascin overexpression by abolishing the interactions between Smad4 and its DNA binding elements, potentially through physical interactions between GATA3 and Smad3/4. Our findings provide mechanistic insight into how TGFβ-mediated cell motility and invasiveness are differentially regulated in breast cancer.
Citation Format: Jianwei Sun, Huifang He, Smitha Pillai, Srikumar Chellappan, Shengyu Yang. GATA3 abrogates TGFbeta-mediated breast cancer invasion and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5001. doi:10.1158/1538-7445.AM2014-5001
Abstract 5002: Modulation of E-cadherin transcription mediated by nuclear localization of ABCG2
Authors: Liang Shu-Ching , Yang Chih-Yung , Lin Chi-Hung 
Published: May 2015

Abstract
Breast cancer resistance protein (BCRP/ABCG2) is a member of ATP binding cassette (ABC) transporter family. Functional overexpression of ABCG2 at plasma membrane in variety of human cancers contributes to multidrug resistance during chemotherapy. Furthermore, previous studies also demonstrate ABCG2 can localize to the intracellular compartments for efflux of its substrates. In addition, ABCG2 is responsible for Hoechst dye efflux pattern and confers the SP cell phenotype in various organs, and to play a role in protecting hematopoietic stem cells. In this study, confocal immunofluorescence microscopy and cellular fractionation showed endogenous ABCG2 localized at nucleus. Thus, we hypothesis the nuclear localization of ABCG2 may play a novel role in stemness-related gene regulation. We established ABCG2 overexpression and knockdown stable cell line by lentivirus infections and performed RNA microarray analysis in A549 cells to elucidate the effect of ABCG2 expression. We reported that ABCG2 can shuttle into the nucleus and bind to E-cadherin promoter, and then regulate E-cadherin expression in lung cancer cells. In addition, ABCG2 was able to affect cell migration and colony formation. These results demonstrated the ABCG2 adds further complexity to play a pivotal role in E-cadherin transcriptional regulation and subsequence decrease cell motility.
Citation Format: Shu-Ching Liang, Chih-Yung Yang, Chi-Hung Lin. Modulation of E-cadherin transcription mediated by nuclear localization of ABCG2. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5002. doi:10.1158/1538-7445.AM2014-5002
Abstract 5003: Functional significance of TIGAR expression in nasopharyngeal carcinoma
Authors: Wong Elaine Y. , Wong SC Cesar , Chan Charles M. , Lam Emily K. , Ho Louisa , Lau Cecilia P. , Au Thomas C. , Chan Amanda K. , Tsang CM , Tsao George S. , Lui Vivian W. , Chan Anthony T. 
Published: May 2015

Abstract
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus associated cancer of the nasopharynx. Annual incidence in China is high, reaching up to 25 per 100,000. NPC is a highly invasive and metastatic disease. At diagnosis, over 60% of patients have advanced disease where treatment failure due to distant recurrence or metastasis is common. More effective forms of therapy to treat this deadly disease are therefore urgently needed.
The TP53 induced glycolysis and apoptosis regulator (TIGAR) is a p53 target gene which blocks glycolysis and promotes cellular metabolism via the pentose phosphate pathway. TIGAR promotes production of cellular nicotinamide adenine dinucleotide phosphate (NADPH), leading to enhanced scavenging of intracellular reactive oxygen species (ROS) and inhibition of oxidative-stress induced apoptosis in normal cells. Previously, we have found that a novel nucleoside analog inhibited cell growth and induced apoptosis in NPC cell lines via down-regulation of TIGAR expression. Moreover, the growth inhibitory effect of c-Met tyrosine kinase inhibitors was ameliorated by over-expression of TIGAR in NPC cell lines. These results are indicative of a pivotal role for TIGAR expression in maintaining NPC cell survival.
In this study, we investigated the expression pattern of TIGAR in NPC tumor tissues and the consequences of TIGAR overexpression and knockdown on NPC cell growth and invasion. It was found that TIGAR is overexpressed in 27 out of 36 (75%) NPC cases in the tumor cells compared to their respective normal epithelial cells. Overexpression of TIGAR in NPC cell lines resulted in increased proliferation, invasion, NADPH production and up-regulation of mesenchymal markers including fibronectin and vimentin. These changes were reversed when TIGAR expression was knocked down by transfection with siRNA, demonstrating specificity of the observed effects. Together, our results indicate that TIGAR expression promotes proliferation, invasiveness and expression of mesenchymal markers in NPC cells. These findings may form the basis for development of a new therapeutic target for treatment of NPC in the future.
Citation Format: Elaine YL Wong, SC Cesar Wong, Charles ML Chan, Emily KY Lam, Louisa Ho, Cecilia PY Lau, Thomas CC Au, Amanda KC Chan, CM Tsang, George SW Tsao, Vivian WY Lui, Anthony TC Chan. Functional significance of TIGAR expression in nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5003. doi:10.1158/1538-7445.AM2014-5003
Abstract 5005: The histone demethylase JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1
Authors: TEE ANDREW E. , CHEUNG BELAMY , MARSHALL GLENN M. , LIU TAO 
Published: May 2015

Abstract
Patients with neuroblastoma due to N-Myc oncogene-amplification die of tumor metastasis. However, it is not clear how N-Myc induces cell migration, invasion and metastasis. The histone demethylase JMJD1A activates target gene transcription by demethylating the lysine 9 residue of histone H3 (H3K9) at target gene promoters, and the long noncoding RNA MALAT1 induces lung cancer cell migration and plays a pivotal role in lung cancer metastasis. Here we demonstrated that N-Myc up-regulated the expression of JMJD1A in N-Myc oncogene-amplified human neuroblastoma cells by directly binding to JMJD1A gene promoter. Affymetrix gene array studies revealed that the gene second most significantly up-regulated by JMJD1A was MALAT1. Consistent with this finding, RT-PCR, chromatin immunoprecipitation and luciferase assays showed that JMJD1A bound to MALAT1 gene promoter, demethylates histone H3K9 at MALAT1 gene promoter and activates MALAT1 promoter activity. Moreover, JMJD1A and MALAT1 induce, while the small molecule JMJD1A inhibitor DMOG suppresses, neuroblastoma cell migration and invasion. Taken together, our data identify a novel pathway through which N-Myc causes neuroblastoma cell migration, invasion and potentially metastasis, and provide important evidence for further development of more potent JMJD1A/MALAT1 inhibitors for the prevention of tumor metastasis.
Note: This abstract was not presented at the meeting.
Citation Format: ANDREW E. TEE, BELAMY CHEUNG, GLENN M. MARSHALL, TAO LIU. The histone demethylase JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5005. doi:10.1158/1538-7445.AM2014-5005