bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3441: A novel lncRNA-mediated YAP1 signaling pathway activation in epithelial ovarian cancer
Authors: Lin Xianzhi , Corona Rosario I. , Gayther Simon A. , Hazelett Dennis L. , Lawrenson Kate 
Published: July 2017

Abstract
Background: The long noncoding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is upregulated in many cancer types, including ovarian cancer. In high grade serous ovarian cancers (HGSOCs), we had previously found that UCA1 expression negatively correlates with patients’ total survival and disease-free survival and that UCA1 knockout significantly impairs tumor growth in vivo. In addition, UCA1 promotes ovarian cancer cell growth via activating the YAP1 signaling pathway.
Purpose: Our present study aims to dissect the molecular mechanisms underlying YAP1 signaling activation by UCA1.
Methods: To characterize the UCA1 interactome, we utilized a modified in vivo RNA antisense purification method (UCA1-iRAP). This UCA1-iRAP method uses streptavidin-coupled magnetic beads to pull down biotin-labeled antisense probes which are complementary to the target RNA. In such a way, UCA1 RNA will be specifically enriched together with its in vivo-associated proteins, RNAs and/or genomic DNA, which can be profiled using mass spectrometry (MS) and next generation sequencing (NGS), respectively.
Results: Using UCA1-iRAP RNA-Seq and UCA1-iRAP protein MS, we comprehensively annotated the UCA1-interacting RNAs as well as UCA1-associated proteins. Interestingly many of the proteins identified were not known to have RNA-binding potential. Integration of NGS and MS data with multilayered functional and molecular characterization of UCA1 knockout, knockdown and overexpression models identified a YAP1 modulator involved in UCA1-mediated regulation of YAP1 signaling. Through repressing this YAP1 modulator via direct RNA-protein interaction, UCA1 promotes nuclear translocation of YAP1, resulting in activation of YAP1 target genes expression.
Conclusions: Our analyses indicate, for the first time, that UCA1 promotes ovarian cancer cell growth by activating YAP1 signaling via direct interaction with a YAP1 modulator. The interaction between UCA1 and this YAP1 modulator leads to activation of YAP1 signaling by nuclear translocation of YAP1. In summary, we characterize a novel UCA1-YAP1 signaling axis active in HGSOCs and also reveal that oncogenic lncRNA’s binding potential of cytoplasmic signaling proteins could be a common mechanism of post-translational control of signaling pathways deregulated in cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Xianzhi Lin, Rosario I. Corona, Simon A. Gayther, Dennis L. Hazelett, Kate Lawrenson. A novel lncRNA-mediated YAP1 signaling pathway activation in epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3441. doi:10.1158/1538-7445.AM2017-3441
Abstract 3451: Depletion of Mastl kinase inhibits cancer growth by induction of mitotic catastrophe in breast cancer
Authors: Yina Yoon , Kim Jae Sung 
Published: July 2017

Abstract
Targeting mitotic kinase is an emerging anticancer strategy with promising pre-clinical results. Mastl is an essential mitotic kinase regulating mitotic progression by inactivation of a tumor suppressor protein phosphatase 2A (PP2A). However, it is unclear whether inhibition of Mastl kinase can kills tumor cells. Here, we show that Mastl inhibition selectively kills cancer cells by induction of mitotic catastrophe in breast cancer cells. We found that Mastl overexpression was tightly associated with tumor progression and poor prognosis in breast cancer. Mastl depletion with specific siRNAs induced cell death in Mastl high breast cancer cells, but not in Mastl low breast cancer cells. Interestingly, Mastl depletion did not affect the viability of normal cells. In addition, Mastl depletion reduced the oncogenic properties of breast cancer cells. Furthermore, we found that Mastl depletion caused mitotic catastrophe. Therefore, our data indicate that inhibition of Mastl can selectively kill breast cancer cells by induction of mitotic catastrophe, providing that targeting Mastl kinase is a very useful approach for breast cancer treatment.
Citation Format: Yoon Yina, Jae Sung Kim. Depletion of Mastl kinase inhibits cancer growth by induction of mitotic catastrophe in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3451. doi:10.1158/1538-7445.AM2017-3451
Abstract 3470: The promyelocytic leukemia (PML) protein modulates rate and localization of homologous recombination in human cell lines with the alternative lengthening of telomeres (ALT) pathway
Authors: Barry Walter , Heaphy Christopher , Meeker Alan 
Published: July 2017

Abstract
The promyelocytic leukemia protein (PML) is tightly associated with a defining feature of the cancer specific, telomerase-independent telomere-maintenance pathway known as alternative lengthening of telomeres (ALT); therefore, PML is an important potential target for chemotherapeutics. Cells running ALT contain large accumulations of telomeric DNA and RNA in the nucleoplasm that are frequently coated in a polymer shell of PML protein. These structures are known as ALT-associated PML bodies (APBs). APBs have been postulated to be major sites of the telomeric sequence homologous recombination believed to be the basis of telomere maintenance in ALT. A CRISPR based strategy was used to knock out the PML gene in two widely used ALT positive osteosarcoma-derived human cell lines; U2OS, and SAOS2. Knockout clones from both cell lines continued to proliferate past passage 90 without crisis, and knockouts were validated at the genetic and protein levels by Sanger sequencing and western blotting, respectively. Chromosome orientation fluorescent in situ hybridization (COFISH) was carried out to determine the number of telomere sequence exchanges occurring in a single cell cycle in these knockouts. A twofold increase in telomere-specific exchanges, presumably telomere sister chromatid exchanges (T-SCE), over the parental line was detected. Intrachromosomal exchanges not specific to telomeres were also analyzed by the harlequin chromosome staining method. A significant increase in these types of exchanges was also observed. In conclusion, the presence of PML is not required for ALT to continue to function, and may be acting to modulate homologous recombination frequency and location in ALT positive cells.
Citation Format: Walter Barry, Christopher Heaphy, Alan Meeker. The promyelocytic leukemia (PML) protein modulates rate and localization of homologous recombination in human cell lines with the alternative lengthening of telomeres (ALT) pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3470. doi:10.1158/1538-7445.AM2017-3470
Abstract 3471: Replication of megabase-size alpha-satellite DNA arrays in human centromere
Authors: Erliandri Indri 
Published: July 2017

Abstract
Alphoid centromere array is composed by 171 bp AT rich alphoid monomer that tandemly arranged into high order repeat unit up to 4 MB array. Hallmark of centromeric DNA is CENPB box, a 17 bp motif that is a binding site of CENPB. As the chromosomal site that regulates the precise and accurate chromosome segregation, understanding DNA replication in centromere will reveal insight into faithful chromosome segregation that potentially influence cellular behavior in normal and cancer cell. The present of active replicons within alphoid centromere array are detected by enrichment of nsDNA abundance. This finding is supported by evident of Orc2, Cdt1 and Treslin accumulation on the alphoid centromere array. Chromatin fiber analysis revealed that inter origin distance within alphoid centromere array is irregular. CENPB depletion that is affected centromeric chromatin structure enhances DNA replication activity within alphoid centromeric array, indicates centromeric chromatin landscape alteration affected centromeric DNA replication dynamic.
Citation Format: Indri Erliandri. Replication of megabase-size alpha-satellite DNA arrays in human centromere [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3471. doi:10.1158/1538-7445.AM2017-3471
Abstract 3473: Functional analysis of the KIF22 in human prostate cancer cells
Authors: Sakamaki Rina , Saito Shungo , Kitano Tatsuya , Nittami Tadashi , Seo Jieun , Takagi Akimitsu , Ishiguro Hitoshi , Uemura Hiroji , Watanabe Masatoshi 
Published: July 2017

Abstract
In the previous study, we identified genes that were differentially expressed between monolayers and spheroids in prostate cancer cell lines. The KIF22 gene was extracted as one of candidate genes related with spheroid formation and multicellular resistance. KIF22 is one of the kinesin superfamily proteins that are microtubule-dependent molecular motor proteins with DNA-binding capacity. KIF22 plays an important role in eukaryotic cell mitosis and macromolecule transportation. Alteration of KIF22 expression and function may lead to cancer development and progression. In this study, we explored the function of the KIF22 in prostate cancer cell lines, DU145 and LNCaP using the KIF22 siRNA. The KIF22 mRNA levels in LNCaP and DU-145 monolayers were detected, and time-dependently increased in both spheroids. The inhibition of KIF22 mRNA using siRNA affected cell proliferation in DU145 and LNCaP spheroids as well as monolayers. In addition, this suppression caused G2/M arrest and apoptosis in both cell lines. In clinical samples, its mRNA expression was significantly higher in tumor portions than in non-cancerous portions. However, the inhibition of KIF22 mRNA did not affect cell migration and invasion in DU145 and LNCaP cells. These findings suggest that KIF22 may play an important role in prostate cancer proliferation, especially spheroid formation, and have the potential to be targeted for prostate cancer treatments such as combination therapy with docetaxel.
Citation Format: Rina Sakamaki, Shungo Saito, Tatsuya Kitano, Tadashi Nittami, Jieun Seo, Akimitsu Takagi, Hitoshi Ishiguro, Hiroji Uemura, Masatoshi Watanabe. Functional analysis of the KIF22 in human prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3473. doi:10.1158/1538-7445.AM2017-3473
Abstract 349: Eribulin induces cortical localization of E-cadherin, p120-catenin and beta-catenin in breast cancer cells
Authors: Clark Alison D. , Dybdal-Hargreaves Nicholas F. , Mooberry Susan L. 
Published: July 2017

Abstract
Eribulin provides a survival advantage for breast cancer patients, particularly those with triple-negative and HER2-negative subtypes.1,2 Mechanistically, eribulin was shown to reverse epithelial-to-mesenchymal transition (EMT) in breast cancer models.3 E-cadherin is a central regulator responsible for maintenance of the epithelial phenotype and loss of cortical E-cadherin and its downstream signaling is an early and significant event in EMT. Short term treatment of HCC1937 breast cancer cells with eribulin initiated cortical E-cadherin localization in manner different from other microtubule targeting agents. Cortical E-cadherin plays essential roles in cell adhesion and in regulating the Wnt pathway, whose aberrant activity is implicated in EMT. At the adherens junctions p120-catenin and β-catenin bind to E-cadherin, an interaction facilitated by microtubules. Cortical sequestration of p120- and β-catenin at the adherens junctions stabilizes these complexes and inhibits their ability to stimulate signaling pathways that contribute to EMT. We tested whether eribulin, which binds to the plus ends of microtubules, promotes EMT reversal by influencing p120- and β-catenin localization and activity. Our results show that eribulin induces cortical localization of p120-catenin and β-catenin with E-cadherin in HCC1937 cells, consistent with the formation of normal adherens junctions. Eribulin also stimulated the phosphorylation of Ser33/37 and Thr41 on β-catenin which promotes proteasomal degradation, which would be expected to further inhibit oncogenic signaling. Collectively, our results suggest that eribulin contributes to reversal of EMT through modulation of downstream signaling initiated by cortical localization of p120- and β-catenin at the adherens junctions. Funding for this work was provided by Eisai Inc.
1. Cortes J., et al., Lancet 377:914-923, 2011
2. Twelves, C., et al., Breast Cancer Res Treat 148:553-561, 2014
3. Yoshida, T., et al., Br J of Cancer 110: 1497-1505, 2014
Citation Format: Alison D. Clark, Nicholas F. Dybdal-Hargreaves, Susan L. Mooberry. Eribulin induces cortical localization of E-cadherin, p120-catenin and beta-catenin in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 349. doi:10.1158/1538-7445.AM2017-349
Abstract 3497: Network-based systematic inference of lncRNA activity in breast cancer
Authors: Ung Matthew , Mattox Daniel , Wang George , Cheng Chao 
Published: July 2017

Abstract
The production of lncRNA is widespread across the human genome, yet the functions of lncRNAs and the phenotypes resulting from their activation have remained largely unstudied. In cancer, several lncRNAs have been found to associate with disease development and poor patient prognosis including HOTAIR and MALAT1. Recent studies have been performed using lncRNA microarrays or re-annotated probes from coding gene microarrays to systematically investigate their roles in cancer. However, datasets from lncRNA microarrays are typically not accompanied by comprehensive clinical information that can be used to draw associations between lncRNA expression and clinical phenotypes. Furthermore, lncRNA stability and cellular localization is highly variable suggesting that expression-based inference of lncRNA activity may not always be an accurate measure of its activity. To address this issue, we introduce an activity-based approach whereby we analyze the expression of lncRNA target genes to infer lncRNA activity. Specifically, we construct a breast cancer specific lncRNA-target gene network from RNA-seq data using a network reconstruction algorithm. We then apply this network to several breast cancer microarray datasets to systematically investigate lncRNA activity and their association with clinical phenotypes. Notably, we find that certain lncRNAs are active in specific molecular subtypes of breast cancer even though their expression levels do not reveal significant differences. Lastly, we performed survival analysis to systematically screen for novel lncRNAs whose activity associate with patient prognosis. Our results suggest that activity-based inference of lncRNAs can identify novel lncRNAs that may serve as therapeutic targets or biomarkers in breast cancer.
Citation Format: Matthew Ung, Daniel Mattox, George Wang, Chao Cheng. Network-based systematic inference of lncRNA activity in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3497. doi:10.1158/1538-7445.AM2017-3497
Abstract 350: Pregnancy at early age is associated with a reduction of progesterone-responsive cells and epithelial Wnt signaling in human breast tissue
Authors: Mechera Robert , Münst Simone , Däster Silvio , Piscuoglio Salvatore , Ng Charlotte , Meier-Abt Fabienne , Weber Walter P. , Soysal Savas D. 
Published: July 2017

Abstract
Background: Pregnancy at early age is the most significant modifiable factor which consistently decreases lifetime breast cancer risk. However, the underlying mechanisms haven’t been conclusively identified. Studies in mice suggest a reduction in progesterone-receptor (PR) sensitive epithelial cells as well as a downregulation of the Wnt signaling pathway as being one of the main mechanisms for the protective effect of early pregnancy. The aim of our study was to validate these findings in humans.
Methods: We collected benign breast tissue of 123 women who had been stratified according to age at first pregnancy and the occurrence of subsequent breast cancer, and performed immunohistochemistry for PR, Wnt4 and the Wnt-target Versican.
Results: The number of PR positive epithelial cells was significantly lower in the group of women with early pregnancy and no subsequent breast cancer compared to the group of nulliparous women with subsequent invasive breast cancer (p=0.017). In women with early pregnancy, expression of Versican and Wnt4 was significantly lower compared to nulliparous women (p=0.0064 and p=0.0156 respectively), and Versican expression was also significant lower compared to women with late pregnancy (p&lt;0.0001).
Discussion: Our results confirm prior observations in mice and suggest a role of downregulation of epithelial Wnt signaling in the protective effect of early pregnancy in humans. This results in a decreased proliferation of stem/progenitor cells; therefore, the Wnt signaling pathway may represent a potential target for breast cancer prevention in humans.
Citation Format: Robert Mechera, Simone Münst, Silvio Däster, Salvatore Piscuoglio, Charlotte Ng, Fabienne Meier-Abt, Walter P. Weber, Savas D. Soysal. Pregnancy at early age is associated with a reduction of progesterone-responsive cells and epithelial Wnt signaling in human breast tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 350. doi:10.1158/1538-7445.AM2017-350
Abstract 3501: Prognostic value of a 4 lncRNA signature in patients with non-small cell lung cancer: a lncRNA expression analysis
Authors: Long XiaoRan , Wang HuiYun , Ge ChunLei , Song Xin , Zhang MeiYin , Zhen XiaoFeng 
Published: July 2017

Abstract
Recently, increasing evidence indicates that lncRNA plays an important role in the cancer development and progression. In this study, we are aimed to identify lncRNA signature for predicting survival of non-small cell lung cancer (NSCLC) patients. A total of 366 NSCLC cases, which were divided into a training and validation set, were detected by lncRNA microarray (containing 2412 lncRNA probes), and another 73 cases as an independent set were analyzed by qRT-PCR. LncRNA microarray analysis identified a total of 305 differentially expressed lncRNAs (138 up-regulated and 167 down-regulated) between NSCLC and normal tissues in the training set. We then validated the microarray data by qRT-PCR analysis of 5 lncRNAs (2 up-regulated and 3 down-regulated) in 30 paired NSCLC and adjacent lung tissues randomly selected from the training set. We then used a stepwise forward process to select the best combination of lncRNAs with the most significance in prediction of NSCLC prognosis and a 4-lncRNA prognostic signature was established, which was significantly associated with overall survival (hazard ratio [HR]: 3.563, 95% confidence interval [CI]: 2.118-5.995, P &lt;0.001) and disease-free survival (HR: 3.236, 95% CI: 2.116-4.940, P &lt;0.001) in the training set. This prognostic signature was validated in the validation (OS, HR: 3.186, 95% CI: 1.849-5.488, P &lt;0.001; DFS, HR: 2.967, 95% CI: 1.949-4.517, P &lt;0.001) and independent sets (OS, HR: 4.703, 95% CI: 1.923-11.50, P &lt;0.001; DFS, HR: 4.549, 95% CI: 2.139-9.674, P &lt;0.001). This 4-lncRNA signature has been demonstrated as an independent prognostic factor, which significantly improves the prognostic accuracy of TNM staging system in a combined model as assessed by ROC curve analyses in the three sets, respectively. Therefore, the 4-lncRNA signature has potential prognostic role in NSCLC patients.
Citation Format: XiaoRan Long, HuiYun Wang, ChunLei Ge, Xin Song, MeiYin Zhang, XiaoFeng Zhen. Prognostic value of a 4 lncRNA signature in patients with non-small cell lung cancer: a lncRNA expression analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3501. doi:10.1158/1538-7445.AM2017-3501
Abstract 3514: Assessing the role of CREB in fibrolamellar hepatocellular carcinoma with PRKACA-DNAJB1 fusion protein
Authors: Karki Anju , LaQuaglia Michael J. , Dios Amanda M. , Sadri-Vakili Ghazaleh , Vakili Khashayar 
Published: July 2017

Abstract
Introduction: Fibrolamellar Hepatocellular Carcinoma (FLHCC) is a rare form of liver cancer that occurs predominantly in adolescents or young adults. Curing or prolonging the lives of patients with FLHCC is extremely challenging. Despite aggressive surgical resections of primary tumors as well as metastatic lesions, outcomes tend to be poor due to lack of effective chemotherapy. Previous studies have demonstrated the presence of PRKACA-DNAJB1 fusion protein in the majority of FLHCC patients. DNAJB1 is a heat shock protein and PKA is a kinase that phosphorylates numerous substrates including cAMP-regulatory element-binding protein (CREB), a proto-oncogenic transcription factor. Therefore, we sought to examine whether the presence of the fusion protein in FLHCC is associated with increased CREB phosphorylation.
Methods: We analyzed tumor and matched non-neoplastic liver tissue from 7 pediatric patients with a pathologic diagnosis of FLHCC. We assessed the presence of the PRKACA-DNAJB1 fusion protein using PKA antibody, as well as total CREB and phosphorylated (p-CREB) using immunoblot analyses with specific antibodies.
Results: Immunoblot analysis using anti-PKA antibody confirmed the occurrence of PRKACA-DNAJB1 fusion transcripts in 6/7 (86%) FLHCC tumor samples. Immunoblot analyses of the 6 patients with the fusion protein revealed a trend towards a decrease in p-CREB expression in tumor samples compared to non-neoplastic tissue controls (p=0.15).
Conclusions: The pattern of p-CREB in FLHCC with PRKACA-DNAJB1 fusion protein suggests that the fusion protein does not exert its proto-oncogenic effects through the transcriptional activity of CREB.
Citation Format: Anju Karki, Michael J. LaQuaglia, Amanda M. Dios, Ghazaleh Sadri-Vakili, Khashayar Vakili. Assessing the role of CREB in fibrolamellar hepatocellular carcinoma with PRKACA-DNAJB1 fusion protein [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3514. doi:10.1158/1538-7445.AM2017-3514