bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A01: Long noncoding RNA H19 regulates growth factor signaling in breast cancer cells
Authors: Vennin Constance , Dhamani Fatima , Spruyt Nathalie , Adriaenssens Eric 
Published: August 2014

Abstract
H19 is one of the earliest identified, and the most studied, long noncoding RNAs. H19 gene is submitted to genomic imprinting and expressed only from the maternal allele and has no protein associated to its transcription. It has been proposed that H19 RNA function as a riboregulator. H19 is essential for development regulation but is also associated with carcinogenesis in many organs. However, biological functions and regulatory mechanisms of this conserved non coding RNA remain largely undecipher. Previously, we have shown that H19 is overexpressed in 70% of human breast cancers. In addition, its over-expression promotes cells invasion and angiogenesis. H19, positively regulated by E2F1, promotes cell cycle progression and G1/S transition. Altogether, these data support oncogenic function in breast tumor genesis of H19.
Recently, H19 has been showed to be a microRNA precursor of miR-675-5p and miR-675-3p. MicroRNAs are small non-coding RNA that regulate expression of up to 60% of genes. However, miR-675 targets have not yet been identified in breast cancer cells.
H19 gene expression is positively regulated by several growth factors, in peculiar hepatocyte growth factor / scatter factor (HGF/SF). HGF/SF stimulates proliferation of epithelial cells and increases both their motility and morphogenesis.
In the present study, in order to explain these phenotypes, we have searched for miR-675 targets in breast cancer cells. We demonstrate that H19, through its microRNA miR-675-5p, regulates negatively the expression of ubiquitin ligase E3 proteins: c-Cbl and Cbl-b. Both these proteins are involved in tyrosine kinase receptor degradation. In all breast cancer cells tested, c-Cbl and Cbl-b expression was significantly decreased after H19 or miR-675 over-expression. This downregulation promotes stability of growth factor receptors (EGFR, c-Met) that sustains and amplifies activation of downstream signaling pathways (Akt, MAP-kinase). Furthermore, we have shown that H19 overexpression increases breast cancer cells migration and invasion. Our data demonstrate that H19 gene overexpression increases HGF/SF receptor signaling as well as associated phenotypes. Our work propose a mechanism of action of H19 in breast cancer in increasing cell invasion and metastasis in this organ. H19 could also be involved in the mechanism of tumor resistance to treatment by increasing paracrine phenomena.
Citation Format: Constance Vennin, Fatima Dhamani, Nathalie Spruyt, Eric Adriaenssens. Long noncoding RNA H19 regulates growth factor signaling in breast cancer cells. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A01.
Abstract A34: A regulatory role of beta-PIX in epidermal growth factor-induced cancer cell migration
Authors: Kuo Jean-Cheng 
Published: August 2014

Abstract
Expression of epidermal growth factor receptor (EGFR) in non–small cell lung cancer (NSCLC) tumors correlates with poor prognosis. EGFR signaling is Src dependent. Activation of EGFR leads to cycles of membrane protrusion, cell adhesion, contraction, and retraction, therefore promoting cell migration. Here, we show a novel role of beta-PIX (Pak-interactive exchange factor) in EGFR-mediated NSCLC cell migration. EGFR signals through Src, which phosphorylates beta-PIX sequentially at two specific tyrosine residues, 442 and 595. Phosphorylation of beta-PIX at tyrosine 442 leads to activation of small GTPase Rac1, which promotes membrane protrusion and cell adhesion assembly around 5 min after EGF stimulation. After another 20 minutes, tyrosine 442 is dephosphorylated, while tyrosine 595 of beta-PIX is phosphorylated. Phosphorylation of tyrosine 595 results in activation of small GTPase RhoA, contraction generation, adhesion disassembly, and cell retraction. These data suggest that the phosphorylation-dephosphorylation cycle of beta-PIX at tyrosine 442 and 595 serves as a regulatory signal downstream of EGFR to control migration and invasion of NSCLC cells.
Note: This abstract was not presented at the conference.
Citation Format: Jean-Cheng Kuo. A regulatory role of beta-PIX in epidermal growth factor-induced cancer cell migration. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A34.
Abstract A41: Inhibition of Lkb1 in cultured embryonic pancreas destabilizes tissue architecture to generate precancerous-like lesions
Authors: Lo Bryan , Viotti Manuel , Strasser Geraldine , Mellman Ira 
Published: August 2014

Abstract
The tumor suppressor Lkb1 is a regulator of cellular energy, proliferation, and polarity, yet the mechanism by which it controls tissue morphogenesis or cancer remains poorly defined. By culturing embryonic tissues from mice harboring a mutant Lkb1 that can be rapidly inhibited, we have previously shown that acute loss of Lkb1 results in destabilized tissue architecture and the formation of highly dynamic pancreatic cysts (Lo et al, JCB 2012). Remarkably, the pancreatic cysts evolve within a few days into precancerous-like lesions that we now demonstrate to have a transcriptional profile that is strikingly similar to those reported for mouse and human PanINs (Pancreatic Intraepithelial Neoplasias). Utilizing fluorescence activated cell sorting, we have begun to track gene expression signatures associated with canonical signaling pathways in both single cells and subsets of cells from the embryonic explants. Since our experimental system offers precise temporal control and accessibility to manipulation within a tissue context, we are able to gain unprecedented insight into the earliest events in pancreatic oncogenesis.
Citation Format: Bryan Lo, Manuel Viotti, Geraldine Strasser, Ira Mellman. Inhibition of Lkb1 in cultured embryonic pancreas destabilizes tissue architecture to generate precancerous-like lesions. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A41.
Abstract A50: Analysis of molecular mechanisms underlying colon cancer development by 3D culture system
Authors: Sakurai Atsuro , Imajo Masamichi , Matsuda Michiyuki 
Published: August 2014

Abstract
Intestinal stem cells produce all types of intestinal epithelial cells including absorptive enterocytes and secretory cells to maintain the homeostasis of intestinal tract. Activity of various signaling pathways not only in the epithelial cells but also in the stromal cells must be coordinately regulated to maintain the intact structure. Among them, Wnt pathway is regarded as one of the most critical pathways for stem cell homeostasis and colon cancer development, in which Wnt signaling is often activated due to mutations in tumor suppressor gene APC. However, it is still unclear how the activation of Wnt pathway causes colon cancer development.
To investigate the mechanisms underlying the colon cancer development, we utilized in vitro crypt culture, which recapitulates three-dimensional epithelial structure comprising of all types of intestinal epithelial cells. To reveal key molecules in colon cancer development upon Wnt activation, we performed microarray analysis of crypts cultured in the presence or absence of Wnt3a or GSK-3β inhibitor, both of which are activators of Wnt pathway. Consequently, we identified fifty genes as the Wnt-activated genes. We knocked down these genes by lentivirus-mediated RNA interference in cultured normal and adenomatous crypts to examine the contribution to the cell growth and crypt formation. This approach will help us to understand the signaling network that regulates the homeostasis of stem cells and the development of colon cancer.
Citation Format: Atsuro Sakurai, Masamichi Imajo, Michiyuki Matsuda. Analysis of molecular mechanisms underlying colon cancer development by 3D culture system. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A50.
Abstract A53: Genetic analysis of semaphorin 5A and plexin-B3 in human glioma
Authors: Jahan Fathima Rifkhana Shah , Lee Alan Yiu Wah 
Published: August 2014

Abstract
Semaphorins are a family of axon guidance molecules, which signal through their co-receptors neuropilins and plexins to subserve various functions in the nervous system, the immune system and during organogenesis. Contrary to their role in development, accumulating evidence suggests the pro- and anti-tumorigenic functions of semaphorins and plexins in different cancer types. Similar to other semaphorins, semaphorin 5A (Sema5A) has recently been implicated in various cancers, though its functions remain ambiguous. Our former study revealed the suppressive effect of Sema5A in glioma cell migration and invasion. Analysis of human glioma specimens revealed a marked down-regulation of Sema5A protein expression in high grade glioblastomas, which are highly infiltrative. Here, we provide evidence that forced expression of Sema5A inhbits glioma cell proliferation by disrupting the cell cycle. Taken together, these findings suggest a tumor suppressor function of Sema5A in glioma. Interestingly, real-time quantitative PCR analysis revealed no significant difference in Sema5A mRNA levels across different grades of glioma. Analysis of Sema5A gene in human glioma specimens detected no mutations but the presence of various alternatively spliced variants that could potentially lead to premature truncation of Sema5A protein. Notably, the predominant Sema5A splice variant is expressed at almost equal level as the wild-type counterpart in the glioma specimens analysed. Ectopic expression of this truncated isoform in fact results in an unstable protein that is targeted for proteasomal degradation. These findings reinforce our hypothesis that reduced Sema5A protein levels in glioblastomas could compromise its suppressive effects in glioma progression.
Citation Format: Fathima Rifkhana Shah Jahan, Alan Yiu Wah Lee. Genetic analysis of semaphorin 5A and plexin-B3 in human glioma. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A53.
Abstract A58: Epigenetic silencing of neurotensin receptor type 1 (NTSR1) in colorectal tumor
Authors: Suzuki Hiromu , Yamamoto Eiichiro , Maruyama Reo , Yamano Hiro-o , Nojima Masanori , Tsuyada Akihiro , Niinuma Takeshi , Sato Akiko , Masahiro Kai 
Published: August 2014

Abstract
Purpose: Aberrant DNA methylation plays important roles in the development of colorectal cancer (CRC), but its involvement in the flat-type colorectal tumors is poorly understood. In the current study, we aimed to understand the molecular basis of laterally spreading tumors (LSTs) which extend laterally and circumferentially rather than vertically along the colonic wall. Methods: Methylation was examined using Methylated CpG island amplification-microarray (MCAM) and bisulfite-pyrosequencing in colorectal tumors (n=214). Expression of NTSR1 was tested using TaqMan RT-PCR. Colony formation, MTT, Matrigel invasion assays and cDNA microarray were performed to analyze the functional of NTSR1. Results: MCAM analysis in LSTs identified a number of frequently methylated genes including neurotensin receptor type 1 (NTSR1), a known oncogene in CRC. LSTs showed elevated NTSR1 methylation levels than other types of colorectal tumors (p &lt; 0.001). Ectopic expression of NTSR1 promoted colon cancer cell growth and invasiveness. Conversely, siRNA-induced knockdown of NTSR1 in CRC cells suppressed proliferation and invasiveness. Conclusions: Our results suggest that methylation of NTSR1 is associated with invasive behavior and lateral growth of colorectal tumors. Methylation of NTSR1 may be a useful marker to predict the growth pattern of colorectal tumors.
Citation Format: Hiromu Suzuki, Eiichiro Yamamoto, Reo Maruyama, Hiro-o Yamano, Masanori Nojima, Akihiro Tsuyada, Takeshi Niinuma, Akiko Sato, Kai Masahiro. Epigenetic silencing of neurotensin receptor type 1 (NTSR1) in colorectal tumor. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A58.
Abstract A59: Protein kinase CK2 regulates β-catenin association to E-cadherin and hence viability and invasion of colorectal cancer cells
Authors: Yefi Roger , Silva Eduardo , Cabello Pablo , Niechi Ignacio , Huerta Hernan , Armisen Ricardo , Fernandez Cristina , Tapia Julio C. 
Published: August 2014

Abstract
The key factor in the canonical Wnt pathway is β-catenin which also functions in cell-cell adhesion forming a complex with E-cadherin at the cell surface. Activation of the canonical Wnt pathway is linked to the release of β-catenin from the cell surface, its cytoplasmic stabilization and nuclear import, followed by increased transcriptional activity on genes normally linked to cancer progression, such as survivin and cyclin D1. We already described that caveolin-1 is a member of this complex (termed CEB for caveolin-1/E-cadherin/β-catenin) which inhibits β-catenin transcriptional activity thereby acting as a tumor suppressor. Conversely, protein kinase CK2 is abnormally elevated in a wide variety of cancers, promoting progression by regulating oncogene and tumor suppressor proteins, but also promoting an elevated β-catenin activity. We already demonstrated that cyclooxygenase-2 (COX-2) is a target of CK2 and its metabolite, prostaglandin E2 (PGE2), is key to up-regulate cell proliferation and apoptosis resistance. However, how CK2, PGE2, and caveolin-1 participate in the mechanism of CK2-mediated colorectal cancer progression is yet unknown. In this work, we hypothesize that CK2 promotes cancer progression by augmenting COX-2 expression and subsequently PGE2 production, which disrupts the putative CEB complex in an autocrine manner, leading to the release of β-catenin and increase of its nuclear activity. This was investigated by determining the presence of CEB complex in DLD-1 colon cancer cells (IP), as well as by evaluating the effect of either PGE2 or a CK2 inhibitor (TBB) on in vitro proliferation (MTS®), apoptosis (Caspase-Glo®) and invasiveness (wound-healing and matrigel assays) of these cancer cells. Our results suggest that the CK2-dependent autocrine production of PGE2 in DLD-1 colon cancer cells promotes the dissociation of caveolin-1 from the CEB complex at the cell surface, allowing β-catenin to be apparently phosphorylated (WB anti-P-antibodies) and released to the cytosol, which increments its nuclear import and transcriptional activity on cancer-related genes. Supported by ICGEB (CRP/CHI10-01) and FONDECYT (11070116, 1120132) grants to J.C.T.
Citation Format: Roger Yefi, Eduardo Silva, Pablo Cabello, Ignacio Niechi, Hernan Huerta, Ricardo Armisen, Cristina Fernandez, Julio C. Tapia. Protein kinase CK2 regulates β-catenin association to E-cadherin and hence viability and invasion of colorectal cancer cells. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A59.
Abstract A66: Insights into the pathogenesis of hyperparathyroidism-jaw tumor syndrome: Deciphering the role of Hrpt2 within bone development
Authors: Droscha Casey J. , Cassandra Diegel , Williams Bart O. 
Published: August 2014

Abstract
Hyper-parathyroidism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder in which patients present with parathyroid adenoma or carcinoma, renal cysts, and fibro-osseous tumors of the maxilla or mandible. HPT-JT is caused by loss of heterozygosity or inactivating mutations within the hyperparathyroidism 2 (HRPT2) gene that encodes the tumor suppressor parafibromin. As a core member of the Polymerase Associated Factors (PAF) complex, parafibromin binds to nuclear β-catenin and is known to associate with RNA Polymerase II to facilitate transcriptional initiation and elongation. Recently, the ability of parafibromin to associate with β-catenin and drive Wnt target gene transcription was found to be dependent on dephosphorylation by protein tyrosine phosphatase 2 (Shp2). Additionally, Bruton's Tyrosine Kinase (BTK) has been identified as a negative regulator of Wnt target gene transcription through interaction with parafibromin. Together, these findings suggest that the phosphorylation status of parafibromin may define its role as a transcriptional repressor or activator.
Our objective is to determine how the phosphorylation status of parafibromin regulates Wnt target gene transcription. As Wnt is well known as a positive regulator of osteogenesis, which plays an important role during HPT-JT, it is also important to decipher the role parafibromin plays within osteoblast differentiation. Conditional deletion of Hrpt2 within mature osteoblasts using osteocalcin-driven Cre results in increased bone mineral density, cortical thickness, and overall stiffness of 3- and 6-month-old murine femurs. In addition, loss of Hrpt2 within mesenchymal progenitors using Dermo1-driven Cre results in embryonic lethality at approximately embryonic day 12.5. However, initial in vitro investigations assessing rates of mineralization and calcium deposition within Hrpt2-null osteoblasts show no significant changes as compared to wildtype controls. From these results, it is clear that parafibromin is essential for embryonic development and is a potential inhibitor of bone mass accrual, yet further investigation as to what genes are being occupied and regulated by parafibromin is needed. These findings will aid in the understanding of bone development and may provide insight into the pathogenesis of HPT-JT.
Citation Format: Casey J. Droscha, Diegel Cassandra, Bart O. Williams. Insights into the pathogenesis of hyperparathyroidism-jaw tumor syndrome: Deciphering the role of Hrpt2 within bone development. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A66.
Abstract A67: Methylation of ESR1 and 14-3-3 sigma promoter in serum as possible biomarkers for screening and diagnosis for breast cancer
Authors: Martinez-Galan Joaquina , Torres-Torres Blanca , Delgado Juan Ramón 
Published: August 2014

Abstract
Background: To investigate the association between gene hypermethylation and the major clinico-pathological features of breast cancer, including diagnosis and treatment response.
Material and Methods: 107 women with breast cancer and 108 control subjects were recruited. Real Time QMS-PCR SYBR green (methylation-specific PCR) was used to analyze the utility of circulating DNA with CpG island hypermethylation of APC, RAR-β, E-Cadherin, ESR1 and 14-3-3 sigma; gene promoter regions as breast cancer biomarkers. Sera were collected in 107 operable breast cancer patients (pts) previously surgery and in 60 of those pts after treatment. Respect controls, 34 had benign breast disease and 74 with no evidence of breast disease.
Results: We found significant differences between breast cancer patients and healthy controls in relative serum levels of methylated gene promoters ESR1 (p = 0.0112) and 14-3-3sigma (p=0.0047). We observed that hypermethylation of these combined two genes differentiated between breast cancer patients and healthy controls (p &lt;0.0001) with a sensitivity of 81% (95% CI: 72–88%) and specificity of 88% (95% CI: 78–94 %). Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p = 0.0179); and presence of methylated 14-3-3-sigma was associated with T3-4 stage (OMS) (p&lt; 0.05) and nodal positive status (p&lt; 0.05). We observed lower methylated ERS1 or 14-3-3-sigma values after surgery, respect pretreatment levels, but without an overall statistically significant difference. With a median follow up of 6 years, we found that patients with a significant decrease of sera methylated levels of both genes after surgery had better time to progression an overall survival respect patients without this observation.
Conclusions: this panel of genes detected in ductal lavage and blood specimens could be useful as markers for early detection of breast carcinoma. These findings cast some doubts on the utility for early cancer diagnosis of highly sensitive techniques to identify hypermethylation of specific gene promoters in DNA extracted from serum. Although numerous issues remain to be resolved, the quantitative measurement of circulating methylated DNA is a promising tool for cancer risk assessment.
Note: This abstract was not presented at the conference.
Citation Format: Joaquina Martinez-Galan, Blanca Torres-Torres, Juan Ramón Delgado. Methylation of ESR1 and 14-3-3 sigma promoter in serum as possible biomarkers for screening and diagnosis for breast cancer. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A67.
Abstract B05: Urothelial carcinoma exosomes contain Del1/EDIL-3 and facilitate bladder cancer progression
Authors: Beckham Carla , Silvers Christopher , Olsen Jayme , Yin Peng-nien , Wu Chia-Hao , Ting Huei-ju , Hagen Fred , Scosyrev Emelian , Messing Edward 
Published: August 2014

Abstract
Small membrane-bound vesicles called exosomes are proving to be critical mediators of tumor progression. Here we show, for the first time, that exosomes isolated from the urine of patients with high-grade bladder cancer facilitate tumor progression and contain the matrix-associated glycoprotein EGF-like repeats and discoidin I-like domains (EDIL-3 aka Del1). EDIL-3 is a well-known tumor-associated angiogenic factor and increased expression of EDIL-3 has been shown in numerous tumors to correlate with poor prognosis. We demonstrate, that exosome-derived EDIL-3 is important for angiogenesis as well as urothelial and endothelial cell migration. Importantly, we show that recombinant (r)EDIL-3 is sufficient to promote migration of human urothelial carcinoma 5637 cells and blockade of either the epidermal growth factor receptor (EGFR) and/or the EGFR signal transduction propagating integrin beta 1 abrogated this effect. These data suggest a novel mechanism by which EDIL-3 may be involved in signal transduction pathways in cancer.
Citation Format: Carla Beckham, Christopher Silvers, Jayme Olsen, Peng-nien Yin, Chia-Hao Wu, Huei-ju Ting, Fred Hagen, Emelian Scosyrev, Edward Messing. Urothelial carcinoma exosomes contain Del1/EDIL-3 and facilitate bladder cancer progression. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B05.