bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3398: Reciprocal regulation of MYB and CXCR4 in pancreatic cancer cells: Potential pathobiological implications
Authors: Srivastava Sanjeev K. , Bhardwaj Arun , Arora Sumit , Singh Seema , Grizzle William E. , Singh Ajay P. 
Published: May 2015

Abstract
Pancreatic cancer remains one of the most lethal malignancies with a median post-diagnosis survival of 3-8 months, and a 5 year survival of ∼6%. The poor outcome from pancreatic cancer is largely due to the presence of locally advanced or metastatic disease at the time of diagnosis. Therefore, it is imperative to identify novel molecular targets driving aggressive and metastatic progression of pancreatic cancer, and build up a better understanding of the underlying molecular mechanisms. In this regard, we have identified that MYB, encoding for an oncogenic transcription factor (a cellular progenitor of v-Myb oncogenes), is overexpressed in majority of pancreatic cancer cases and cell lines. Furthermore, our data from gain and loss of function studies (in BxPC3 and MiaPaCa cells, respectively) show that MYB overexpression is associated with pancreatic tumor growth and metastasis. From the mechanistic standpoint, we observe that MYB regulates the expression of CXCR4 through direct binding to its promoter. MYB-overexpressing BxPC3 cells exhibit significantly enhanced migration and invasion against a CXCL12 (sole ligand for CXCR4) gradient, whereas it is suppressed in MYB-silenced MiaPaCa cells as compared to their respective control cells. Furthermore, MYB-overexpressing cells exhibit greater resistance to serum-deprivation in CXCL12-supplemeted media, an effect that is abrogated upon CXCR4 silencing. Interestingly, in parallel studies, we have observed that treatment with CXCL12 also leads to MYB upregulation in pancreatic cancer cells in a CXCR4 dependent manner. Together, these data are suggestive of a novel positive feedback regulatory loop between CXCR4 and MYB and hold important significance for pancreatic cancer pathobiology.
Citation Format: Sanjeev K. Srivastava, Arun Bhardwaj, Sumit Arora, Seema Singh, William E. Grizzle, Ajay P. Singh. Reciprocal regulation of MYB and CXCR4 in pancreatic cancer cells: Potential pathobiological implications. [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 3398. doi:10.1158/1538-7445.AM2014-3398
Abstract 3399: Detection and validation of novel RNA cancer biomarkers by single molecule RNA fluorescence in situ hybridization (smRNA FISH)
Authors: Johansson Hans E. , Orjalo Arturo V. , Coassin Sally R. , Yin Raymund 
Published: May 2015

Abstract
RNA biomarkers are discovered and validated through advanced transcriptome analysis at a fast pace. These markers that allow the interrogation of the active genes hold promise for more precise staging, prognosis, and treatment of cancer. Long RNA markers comprise pre-mRNAs found in the cell nucleus, long non-coding RNAs (lncRNAs) that may be found in both the nucleus and the cytoplasm, as well as mature and mostly cytoplasmic mRNAs. Importantly, comparative studies in mouse have demonstrated that transcript levels are more strongly correlated with clinical traits than the corresponding protein levels. Because lncRNA and mRNA biomarkers have the potential to contribute to the development of targeted cancer therapies, there is an obvious need for a robust and dependable methodology to reliably detect and validate these RNA targets. RNA fluorescence in situ hybridization (RNA FISH) provides a powerful means to detect specific RNAs in single cells, while still maintaining tissue morphology. Significant advances in RNA FISH technology, such as the hybridization of multiple, fluorescently labeled 20-mer oligonucleotides to the RNA target, allow for the detection of single RNAs and yields information on the RNA's distinct spatial distribution within tissues and even within cells. In this study, we investigate emerging RNA biomarkers in prostate cancer cell lines and tissue utilizing RNA FISH. We also examine established breast cancer biomarkers such as human epidermal growth factor receptor 2 (HER2 / ERBB2), estrogen receptor α (ER α / ESR1), and progesterone receptor (PR / PGR) in breast cancer tumors and cell lines. The results and tools presented here will contribute to advancing the current capabilities of the detection and treatment of specific cancers, as well as in the continued discovery and development of cancer drug candidates.
Citation Format: Hans E. Johansson, Arturo V. Orjalo, Sally R. Coassin, Raymund Yin. Detection and validation of novel RNA cancer biomarkers by single molecule RNA fluorescence in situ hybridization (smRNA FISH). [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 3399. doi:10.1158/1538-7445.AM2014-3399
Abstract 3404: Identifying genes involved in retinoic-acid-mediated breast tumor progression by total-genome-knockdown screen
Authors: Coyle Krysta M. , Dean Cheryl , Pan Lu-Zhe , Ahn Dae-Gyun , Sultan Mohammad , Salsman Jayme , Dellaire Graham , Giacomantonio Carman , Lee Patrick W. , Marcato Paola 
Published: May 2015

Abstract
Despite numerous advances in cancer care, breast cancer remains one of the leading causes of cancer-related death among Canadian women. Previous work by our lab has identified aldehyde dehydrogenase 1A3 (ALDH1A3) as a breast cancer stem cell marker, and patients with high levels of ALDH1A3 in their tumors have worse outcomes. Furthermore, we found that via its retinoic acid (RA) production function, ALDH1A3 also contributes to breast tumor growth and metastasis in a murine xenograft model. RA induces transcription of many genes (directly and indirectly), initiates cell signaling and regulates many cellular processes involved in cell growth and differentiation. To identify the key RA-inducible genes which mediate breast cancer progression we performed a genome-wide lentiviral-based shRNA screen using MDA-MB-231 breast cancer cells xenotransplanted into NOD/SCID mice with or without RA treatment. From the in vivo screen, 50 genes were identified as being putatively involved in RA-mediated breast tumor growth. 14 genes have been confirmed in vitro as differentially expressed in the presence of RA. We have generated individual shRNA knockdown clones of the genes and are validating their involvement in RA-mediated breast cancer progression in vivo. Analysis of the genes identified by this screen revealed potential interactions between RA and Wnt signaling, implicating extensive cross-talk between these two pathways. Completion of this study will define the mechanism of RA-mediated breast cancer progression and potentially identify new therapeutic targets for breast cancer treatment.
Citation Format: Krysta M. Coyle, Cheryl Dean, Lu-Zhe Pan, Dae-Gyun Ahn, Mohammad Sultan, Jayme Salsman, Graham Dellaire, Carman Giacomantonio, Patrick W. Lee, Paola Marcato. Identifying genes involved in retinoic-acid-mediated breast tumor progression by total-genome-knockdown screen. [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 3404. doi:10.1158/1538-7445.AM2014-3404
Abstract 3407: Regulation of c-Myc and p53 by splicing factor SRp20
Authors: He Xiaolong , Yang Jilai , Wang Shijie 
Published: May 2015

Abstract
SRp20 is a member of the highly conserved SR protein family of splicing regulators. Our previous study found that SRp20 was overexpressed in ovarian and breast tumors compared to corresponding normal tissues and knockdown of SRp20 expression inhibited tumor cell growth. Suppression of SRp20 by 90% triggered apoptosis of tumor cells through intrinsic pathway, which was accompanied by a downregulation of anti-apoptotic protein, Bcl-2. However, it is unclear what mechanism mediates the induction of apoptosis and downregulation of Bcl-2 by SRp20 knockdown. To address this question, we conducted microarray analysis to identify the genes whose expression or splicing are altered in SRp20-knockdown A2780 cells. Among hundreds of identified genes, the expression of c-Myc and p53 was downregulated. The downregulation was further validated by quantitative PCR. Because of the fundamental importance of p53 and c-Myc in cancer biology and apoptosis, we further examined the expression of these two genes at protein levels. Western blotting showed that p53 is upregulated at protein level in SRp20 knockdown cells, contradictory to its expression at the mRNA level, while the expression of c-Myc is consistent at the protein level and at the mRNA level. These results suggest that SRp20 knockdown-induced apoptosis could be mediated by upregulated p53 protein or reduced c-Myc or both, given already established connection between these two proteins and apoptosis. How SRp20 is involved in the regulation of p53 and c-Myc remains to be determined and is currently under investigation.
Citation Format: Xiaolong He, Jilai Yang, Shijie Wang. Regulation of c-Myc and p53 by splicing factor SRp20. [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 3407. doi:10.1158/1538-7445.AM2014-3407
Abstract 341: Imatinib induces expression of Bim and apoptosis in chronic myelogenous leukemia cells via p38/H2AX pathway
Authors: Xiong Min , Niu Tianhui , Dong Yaqiong , Lu Chengrong 
Published: May 2015

Abstract
H2AX is a novel human tumor suppressor protein and plays an important role in apoptosis of cancer cells. Increasing published data indicate that H2AX phosphorylation (Ser139) contributes to its regulation of cancer cell apoptosis. Thus, charactering the mechanisms and signaling pathways involved in H2AX phosphorylation (Ser139) will certainly provide better understanding on H2AX function in cancer cells. Our previous report showed that caspase-3/Mst1 pathway regulates phosphorylation of H2AX at Ser139 in chronic myelogenous leukemia (CML) cells. Recently we found another pathway which regulates H2AX phosphorylation (Ser139) in CML cells. When the CML cells were subjected to imatinib treatment, MAPK family member ERK1/2 activity was inhibited, but p38 activity was increased, another member JNK1/2 had no response. Then we used p38 inhibitor SB202190 and siRNA against p38 to block p38 activation and observed that H2AX phosphorylation and apoptosis of CML cells was concurrently inhibited. Our results also showed that inhibition of MSK1/MSK2 did not affect H2AX phosphorylation (Ser139), although the p38 and ERK1/2 downstream MSK1/MSK2 could be activated by imatinib in CML cells. Overall, these data confirmed that p38 signaling pathway is also required for H2AX phosphorylation (Ser139) in CML cells. Our further evidences indicated that inhibition of H2AX phosphorylation (Ser139) regulated by p38 during apoptotic induction with imatinib suppressed the expression of apoptosis-related gene Bim. Taken together, these data demonstrated that p38/H2AX pathway regulates Bim expression and subsequent apoptosis in CML cells.
Citation Format: Min Xiong, Tianhui Niu, Yaqiong Dong, Chengrong Lu. Imatinib induces expression of Bim and apoptosis in chronic myelogenous leukemia cells via p38/H2AX pathway. [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 341. doi:10.1158/1538-7445.AM2014-341
Abstract 3410: A novel regulatory region of the MYC oncogene decreases Myc transcriptional activity
Authors: Kalkat Manpreet , Wasylishen Amanda , Chan Pak-Kei Michael , Pandyra Aleksandra , Kim Sam Sulgi , Bros Christina , Raught Brian , Penn Linda Z. 
Published: May 2015

Abstract
MYC is a transcription factor that contributes to over 50% of cancers. While deregulated protein expression of MYC is an important factor driving tumorigenesis, remarkably little is known about the post-translational modifications (PTMs) that are necessary for MYC to function as an active oncogene. Given the important role of PTMs in the regulation of protein activity and stability, our overall objective is to further characterize novel PTMs of MYC, and the functional contribution of these modifications to the ability of the MYC to transform cells. Using a structure-function approach, we have identified six C-terminal lysines that can modulate the ability of MYC to transform cells. By utilizing lysine to arginine mutations (6KR) to abrogate signaling through these residues, we show that MYC 6KR increases anchorage-independent colony growth compared with MYC-WT. Moreover, this mutant was also more potent than WT in promoting xenograft tumour growth. Through target gene expression analysis and luciferase reporter assays, we show that 6KR has enhanced transcriptional activity compared with MYC-WT. To characterize the modifications that can occur at these lysine residues, we have performed mass spectrometry analysis and have identified a number of PTMs that can occur in this region. Furthermore, we have conducted BioID to identify MYC interactors that change in association with 6KR MYC compared to MYC-WT. We theorize that identifying the signaling pathways leading to post-translational modification of this region will be an important first step in the development of inhibitors targeting MYC induced transformation.
Citation Format: Manpreet Kalkat, Amanda Wasylishen, Pak-Kei Michael Chan, Aleksandra Pandyra, Sam Sulgi Kim, Christina Bros, Brian Raught, Linda Z. Penn. A novel regulatory region of the MYC oncogene decreases Myc transcriptional activity. [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 3410. doi:10.1158/1538-7445.AM2014-3410
Abstract 3413: A genetic analysis of splicing in neuroblastoma identifies opposing functions for FUBP1 splice variants in MYC regulation
Authors: Chen Justin , Hackett Christopher S. , Zhang Shile , Song Young K. , Molinaro Annette , Quigley David A. , Balmain Allan , Gustafson William C. , Dyke Terry A. Van , Kwok Pui-Yan , Khan Javed , Weiss William A. 
Published: May 2015

Abstract
Neuroblastoma, a tumor of the peripheral neural crest, is the most common cancer of infancy and the most common extracranial solid tumor of childhood. Large scale sequencing efforts have identified recurrent mutations in only a handful of genes in a minority of patients, but these efforts have so far focused on the exome, limiting identification of mutations leading to changes in alternative splicing.
Regulation of alternative splicing is a critical and tightly regulated cellular function involving a complex interplay between cis-acting sequences on the pre-mRNA transcript and accessory trans-acting splicing factors. To elucidate genetic control of splicing, we used a splicing quantitative trait loci (sQTL) analysis in a backcrossed mouse model of neuroblastoma. We utilized Affymetrix Exon Arrays to profile mRNA expression at the exon level for superior cervical ganglia and cerebella (n=102) which we coupled with genotypes at 350 SNP and microsattlelite locations. With whole-genome sequencing data available for the inbred parental strains, our approach provided us with localized sequences for each individual mouse.
In addition to identifying novel candidate trans-acting splicing factors, these sQTL identify novel candidate intronic regulatory sequences critical for splicing and reveal strain-specific splicing events leading to functional consequences in neuroblastoma. Among these, we show that a subtle splicing event within FUBP1 modulates levels of the MYC oncoprotein in human neuroblastoma-derived cell lines and correlates with outcome in children with neuroblastoma.
Citation Format: Justin Chen, Christopher S. Hackett, Shile Zhang, Young K. Song, Annette Molinaro, David A. Quigley, Allan Balmain, William C. Gustafson, Terry A. Van Dyke, Pui-Yan Kwok, Javed Khan, William A. Weiss. A genetic analysis of splicing in neuroblastoma identifies opposing functions for FUBP1 splice variants in MYC regulation. [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 3413. doi:10.1158/1538-7445.AM2014-3413
Abstract 3414: Genomic signatures of melanoma maintenance
Authors: Sherbaf Faranak Ghazi , Inaki Koichiro , Bertrand Denis , Woo Xing Y. , Hoon Dave , Hillmer Axel , Liu Edison 
Published: May 2015

Abstract
Melanoma is the malignant tumor of melanocytes and considered as one of the most aggressive human cancers. While the worldwide incidence rate of melanoma has increased during the last decade, current therapies for melanoma do not provide long-term effect. The highly heterogeneous expression signature of melanoma underlies the inefficient therapy and accentuates the inevitability of profound molecular understanding of melanoma, its maintenance and progression. In this study, we aimed to reveal the complex patterns of distinct molecular mechanisms underlying the progression and maintenance of melanoma using high-throughput sequencing technologies. Series of melanoma tumor tissues representing discrete stages of the malignant progression were deeply sequenced. Integrative analysis revealed hard-wired genomic aberrations and associated transcriptomic consequences. These genomic aberrations included clusters of oncogenes brought together by structural variations, which cooperated in their amplifications and subsequent up-regulated expressions. We believe that these hard-wired genetic changes are biologically significant; they sustain the survival of the tumor and offer the advantage of the distant metastasis. We reconstituted the architecture of melanoma progression and maintenance and we identified gene cassettes with a putative role in sustaining tumor growth. The correlation of these gene cassettes with the cancer phenotype and the feasibility of these putative oncogenes as candidates for targeted therapy were addressed using cell-based assays on a high content screening platform. Analysis of the matched cell lines derived from the same patient offered a valuable resource for in vitro manipulation, testing of drugs and functional validation. A detailed molecular characterization of the functionally validated genes and their contribution in the cancer signaling pathways will provide a better understanding of the molecular basis of tumor evolution.
Citation Format: Faranak Ghazi Sherbaf, Koichiro Inaki, Denis Bertrand, Xing Yi Woo, Dave Hoon, Axel Hillmer, Edison Liu. Genomic signatures of melanoma maintenance. [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 3414. doi:10.1158/1538-7445.AM2014-3414
Abstract 3416: Transcriptome analysis of papillary thyroid cancer using next-generation sequencing technologies in Korean patients
Authors: Lee Seungbok , Jee Hyeon-Gun , Lee Kyu Eun , Seo Jeong-Sun 
Published: May 2015

Abstract
Thyroid cancer is one of the most prevalent cancers worldwide, and papillary thyroid cancer (PTC) accounts for &gt;80% of all thyroid cancers. Here we conducted RNA sequencing for 70 PTC and 42 paired-normal tissues in Korean patients, and their transcriptomes were analyzed in various aspects. First, somatic mutations were screened transcriptome-wide throughout samples; BRAF mutation (V600E), which is the most well-established mutation in thyroid cancer, was detected in 47 samples out of 70 (67.14%). HRAS (Q61R, Q61K) and NRAS (Q61R) mutations were shown in two samples, respectively. In gene fusion analysis, we discovered four fusion mutations using our stringent criteria and these include CCDC6-RET and PAX8-PPARG fusions, which have been previously reported for thyroid cancer. Other EZR-ERBB4 and PAX8-GLIS3 fusions are novel fusion mutations found in PTC, and the sample having EZR-ERBB4 mutation was diagnosed as the follicular variant subtype. This is an in-frame mutation and previous reports have shown that ERBB4 is a driver gene for carcinogenesis in multiple types of cancers. In addition, we also found ETV6-NTRK3 fusion in less conservative criteria, which was a well-known fusion in other cancer types. Each fusion mutation above was shown in only one sample, respectively. Through gene expression analysis, we clustered PTC cancer samples into four groups; three of them are shown to be enriched with BRAF V600E mutation, and the other includes samples with NRAS, HRAS mutation. In this study, we thoroughly explored the transcriptome of PTC samples using the next-generation sequencing method and proved well-correlation between mutation and expression profiles. These results not only replicated several findings of previous studies and suggested some novel genes or pathways involved in the PTC development in Koreans.
Citation Format: Seungbok Lee, Hyeon-Gun Jee, Kyu Eun Lee, Jeong-Sun Seo. Transcriptome analysis of papillary thyroid cancer using next-generation sequencing technologies in Korean patients. [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 3416. doi:10.1158/1538-7445.AM2014-3416