bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A39: BACH1 and RKIP participate in a bistable network that affects progression to metastasis in breast Cancer
Authors: Lee Jiyoung , Yun Jieun , Yeung Kam , Bevilacqua Elena , Balázsi Gábor , Rosner Marsha Rich 
Published: August 2014

Abstract
The sources of nongenetic variability in metastatic progression are largely unknown. To address this question, we characterized a transcriptional regulatory network for the metastasis suppressor Raf Kinase Inhibitory Protein (RKIP). We previously showed that the transcription factor BACH1 is negatively regulated by RKIP, promotes breast cancer metastasis, and negatively correlates with RKIP expression in primary breast tumors. Here we demonstrate that BACH1 acts in a double negative (overall positive) feedback loop to inhibit RKIP transcription in breast cancer cells. BACH1 also negatively regulates its own transcription. HDAC inhibitors increased BACH1 but not RKIP transcription, whereas depletion of polycomb repressor EZH2 induced RKIP transcription. Analysis of the BACH1 network reveals the existence of a bistable, inverse relationship between BACH1 and RKIP that can potentially give rise to nongenetic variability. Together, our results suggest that the balance between RKIP and BACH1 plays a key role in determining metastatic progression in breast cancers.
Citation Format: Jiyoung Lee, Jieun Yun, Kam Yeung, Elena Bevilacqua, Gábor Balázsi, Marsha Rich Rosner. BACH1 and RKIP participate in a bistable network that affects progression to metastasis in 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 A39.
Abstract A40: CTEN prolongs EGFR signaling by reducing ligand-induced EGFR degradation
Authors: Hong Shiao-Ya , Shih Yi-Ping , Li Tianhong , Carraway Kermit , Lo Su Hao 
Published: August 2014

Abstract
Epidermal growth factor receptor (EGFR) tyrosine kinase engages a vast array of signaling pathways regulating tissue development and homeostasis. The signal is normally induced by ligand binding (such as EGF) that activates the receptors and then the downstream molecules, which mediate cell fate decisions such as proliferation, migration, and differentiation. EGF binding not only turns on the EGFR activity; it also turns on the mechanisms to inactivate EGFR signaling. One way is the activation of c-Cbl, an E3 ubiquitin ligase that binds to tyrosine-phosphorylated EGFR and leads to ubiquitination of EGFR for lysosomal degradation. Dysregulated EGFR signaling either by up-regulation or aberrant activation of the receptor will trigger cellular events that contribute to tumor microenvironments and cancer formation.
Focal adhesions connect extracellular matrix to cytoskeletal networks and play critical roles in cell adhesion, migration, proliferation, and survival. They also crosstalk with growth factor receptors, such as EGFR to elicit a wider range of cellular responses, and may function as biosensors for microenvironments. Cten (C-terminal tensin like) is a focal adhesion molecule known to regulate cell adhesion and migration. Previously, we had shown that cten was up-regulated by EGF and mediated EGF induced cell migration. To further investigate cten's role in EGFR signaling pathway, we examined cten's effect on EGFR protein stability. Cten significantly reduced ligand-induced EGFR degradation through decreasing EGFR ubiquitination. This was accomplished by binding to c-Cbl in a phosphotyrosine-SH2 dependent fashion. A functional SH2 domain of cten was essential for its activities in promoting tumor cell migration, invasion, and colony formation. In addition to cell culture systems, EGFR levels were markedly enhanced in a cten tissue-specific knockin mouse model. By analysis of cten and EGFR expressions in human cancer samples, we found a positive association between cten and EGFR protein levels. Since cten regulates the activated EGFR level and plays roles in tumor migration/invasion, targeting of cten might have a beneficial effect on EGFR targeted therapies.
Citation Format: Shiao-Ya Hong, Yi-Ping Shih, Tianhong Li, Kermit Carraway, Su Hao Lo. CTEN prolongs EGFR signaling by reducing ligand-induced EGFR degradation. [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 A40.
Abstract A52: Loss of p120-catenin induces metastatic progression of breast cancer by inducing anoikis resistance and augmenting growth factor receptor signaling
Authors: Schackmann Ron C.J. , Klarenbeek Sjoerd , Vlug Eva J. , Stelloo Suzan , Amersfoort Miranda van , Tenhagen Milou , Braumuller Tanya M. , Vermeulen Jeroen F. , Groep Petra van der , Peeters Ton , Wall Elsken van der , Diest Paul J. van , Jonkers Jos , Derksen Patrick W.B. 
Published: August 2014

Abstract
The formation of metastasis is the most common cause of breast cancer-related death among women worldwide. A hallmark event in the dissemination of tumor cells from the primary tumor is the loss of cell-cell adhesion. Normally, epithelial integrity is controlled by the adherens junction (AJ), a membrane-tethered structure consisting of E-cadherin and its associated catenins αE-catenin, β-catenin and p120-catenin (p120). Loss of E-cadherin, which results in inactivation of the AJ, is strongly linked to tumor progression. However, little is known about the underlying mechanisms that drive tumor invasion and metastasis.
Since p120-catenin (p120) controls E-cadherin turnover at the cell membrane, we investigated the possible tumor suppressor functions of p120 in breast cancer. First, we analyzed a comprehensive set of invasive breast cancers using immunohistochemistry, and observed a lack of p120 protein expression in 33% (97/296). Next, we used a conditional mouse model of noninvasive (p53-driven) mammary carcinoma and introduced a conditional p120 allele. Combined loss of p120 and p53 resulted in tumors that resembled human metaplastic breast cancer and metastasize to lungs and lymph nodes. Knockdown of p120 in in anchorage-dependent breast cancer cell lines induces anoikis resistance by increasing sensitivity to growth factors. Interestingly, we observed secretion of inflammatory cytokines upon knockdown of p120. These cytokines likely underlie the formation of the prometastatic microenvironment in p120 negative mammary carcinomas, which in turn facilitate the production of growth factors. Finally, we performed RNA sequencing on p120-ablated cells and uncovered several highly up regulated growth factor receptors, which we will further examine to determine their eligibility as targets for intervention strategies to better treat p120-negative metastatic breast cancers.
Citation Format: Ron C.J. Schackmann, Sjoerd Klarenbeek, Eva J. Vlug, Suzan Stelloo, Miranda van Amersfoort, Milou Tenhagen, Tanya M. Braumuller, Jeroen F. Vermeulen, Petra van der Groep, Ton Peeters, Elsken van der Wall, Paul J. van Diest, Jos Jonkers, Patrick W.B. Derksen. Loss of p120-catenin induces metastatic progression of breast cancer by inducing anoikis resistance and augmenting growth factor receptor signaling. [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 A52.
Abstract B01: Impacts of inulin on bile acids induced colon cancer
Authors: Afolabi Bene Akromaa , Appiah Sandra , Pachenari Azra , Ghali Lucy 
Published: August 2014

Abstract
Bile acids are normal components of the luminal contents of gastrointestinal tract but have been reported to cause oxidative damage by stimulating the generation of free oxygen radicals from the mitochondria. Several studies have demonstrated the contribution of reactive species to mutagenesis, carcinogenesis and tumor promotion. There is accumulating evidence to show that some carbohydrates and carbohydrate-containing molecules possess antioxidant ability by inhibiting the production of reactive species. Prebiotics are complex carbohydrates which have been shown to improve gut health when used in combination with probiotics. However, there is paucity of data on how prebiotics alone affect gut health and by which mechanism of action. The reactive oxygen scavenging ability of inulin, a prebiotic, has been shown in vitro in non-cell based system and in mice. The anti-inflammatory effect, through production of short chain fatty acids by fermentable inulin has also been shown. However, the mechanism of inulin in the amelioration of bile acid induced cancer remains unknown.
Methods: Three different cell-lines (colon stem cells, human colon carcinoma cells-HCT-116 and control normal colon epithelial cells) will be examined. Cells will be treated separately with secondary bile acids, primary bile acids and prebiotics. Cells will also be treated with microorganisms' filtrate such as probiotics (bifidobacteria) in conjunction with secondary bile acids, primary bile acids or prebiotics. Production of free radicals will be measured using nitro blue tetrazolium chloride assay (NBT) and inflammatory proteins will be measured using RT-PCR. DNA damage will be assessed using Endonuclease 111 enzyme modified Comet assay. In addition, C1 Single-Cell auto pep system will be used for mRNA sequencing of individual cells within the well plate.
This study hypothesized that normal cells exposed to secondary bile acids in the presence of inulin may be protected from transformation to cancer cells and this may correlate with decrease in production of reactive radicals and pro-inflammatory proteins. The anti inflammatory ability of short chain fatty acid and antioxidant ability of inulin may possibly be associated with AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (P13-K), NF-κB signaling pathways. Thus inulin and their fermentation/breakdown products may not only stimulate beneficial bacteria in the colon but may directly interfere with absorption and cellular metabolism processes in the colon.
Citation Format: Bene Akromaa Afolabi, Sandra Appiah, Azra Pachenari, Lucy Ghali. Impacts of inulin on bile acids induced colon 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 B01.
Abstract B03: Stromal cells confer drug resistance to breast cancer cells in a kinetic co-culture model
Authors: Artymovich Katherine , Szybut Clare , Patel Kalpana , O'Callaghan Tim , Dale Tim , Trezise Del , Appledorn Daniel M. 
Published: August 2014

Abstract
The tumor microenvironment is fundamentally involved in the response of a tumor to anti-cancer therapies. In this study, we present a novel method for kinetically measuring the proliferation of one or more cell types in mixed, co-culture models. Specifically, lentiviral based reagents are used to label nuclei of multiple cell populations within a single culture. Real time cell counts are acquired using an automated, Live Content Imaging approach in which 96-well and 384-well microplates are imaged every 2-3 hours over the course of the full 2-3 day assay. Using this strategy, we confirm data illustrating that culturing HER-2 positive breast cancer cells (SK-BR-3) in the presence of either Human Mammary Fibroblasts (HMFs) or normal skin fibroblasts (CCD-1068Sk) are resistant to the anti-proliferative and cytotoxic effects of the HER-2 and EGFR tyrosine kinase inhibitor lapatinib. Extending this data, we also completed pharmacolgical analyses, using area under the curve of the full kinetic trace, revealing nearly a 2-log difference in lapatinib sensitivity between SK-BR-3 cells grown in the presence or absence lapatinib. The data presented here reveal a novel, automated, kinetic assay for measuring proliferation of one or more cell types in mixed culture models. More importantly, these data further clarify the pharmacolgical effect stromal cells can have on the resistance of breast cancer cells to lapatinib treatment.
Citation Format: Katherine Artymovich, Clare Szybut, Kalpana Patel, Tim O'Callaghan, Tim Dale, Del Trezise, Daniel M. Appledorn. Stromal cells confer drug resistance to breast cancer cells in a kinetic co-culture model. [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 B03.
Abstract B28: Pro-survival role of p53 in regulating epidermal differentiation
Authors: Kracikova Martina , Akiri Gal , Aaronson Stuart A. 
Published: August 2014

Abstract
It is well established that in response to diverse stress signals, the p53 tumor suppressor prevents growth of abnormal cells by inducing senescence or apoptosis. However, recent studies have shown that p53 can contribute to pro-survival pathways such as innate immune response, metabolic regulation and antioxidant defense against reactive-oxygen species (ROS). Here we demonstrate a novel role of p53 in regulating an epidermal differentiation program. Using microarray and real-time PCR, we found that p53 activates the expression of genes within the human and mouse epidermal differentiation complex (EDC), including genes within the cornified envelope precursor family and the fused gene family. Chromatin immunoprecipitation and luciferase reporter assay demonstrated direct p53 binding and activation of a cornified envelope precursor gene. Activation of p53 by ultraviolet B (UVB) radiation or via nutlin-3 led to a dose-dependent increase in expression of those genes, and this increase was inhibited in cells with downregulated p53. The p53-dependent expression of the EDC genes was not limited to keratinocytes, but also detected in other cell types, suggesting additional functions of these genes normally attributed to keratinocyte differentiation and formation of the cornified envelope. These findings identify a novel p53-regulated differentiation pathway and suggest that differentiation may be another pro-survival component of its tumor suppressor function.
Citation Format: Martina Kracikova, Gal Akiri, Stuart A. Aaronson. Pro-survival role of p53 in regulating epidermal differentiation. [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 B28.
Abstract B34: The impact of chromosome 17p loss on cancer
Authors: Liu Yu , Scuoppo Claudio , Lowe Scott 
Published: August 2014

Abstract
Chromosome 17p deletions are associated with short survival and poor response to current chemotherapy treatment in non-Hodgkin's lymphomas. Although the prevailing view is that these deletions serve as a “second hit” event to inactivate p53, these deletions often hundreds of other genes. Using an in vivo RNAi screening approach for tumor suppressor genes, we identified and validated two additional tumor suppressors adjacent to p53 suggesting these deletions may do more than merely inactivate p53. To test this hypothesis, we constructed a new mouse model conditionally targeting a broad region of 17p and are intending to investigate whether and how genes co-deleted with well-known tumor suppressor p53 affect lymphoma development and chemotherapy responses. These results will elucidate the aggressive nature of tumors harboring 17p deletions and create the first mouse model that can be used to test strategies to overcome its deleterious effects.
Citation Format: Yu Liu, Claudio Scuoppo, Scott Lowe. The impact of chromosome 17p loss on 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 B34.
Abstract B62: Proteomic dynamics of stromal exosomes during processing in cancer cells
Authors: Underhill Ainsley Q. , Zhang Yingyi Amy , Zhang Liang , Luga Valbona , Wrana Jeff 
Published: August 2014

Abstract
Within the tumor microenvironment, cancer-associated fibroblasts (CAFs) are capable of releasing exosomes, small extracellular vesicles, which are then used by breast cancer cells to aid in metastasis. Exosomes are uptaken by the cancer cells and gain Wnt11 through processing, thus allowing them to stimulate Wnt-signaling pathways that causes increased cell motility. Our current research has focused on understanding the events that exosomes undergo as they pass through breast cancer cells. Exosomes from L cells carry the tetraspanin, Cd81, and two of its known transmembrane interactors Igsf8 and Ptgfrn. By using immunoprecipitation, we were able to isolate Cd81-exosomes, and analyze them by mass spectrometry. Furthermore, comparison of Cd81-exosomes before and after processing in MDA-MB-231, a human breast cancer cell line, revealed differences in protein content of the exosomes. Additionally, since L cells are a mouse fibroblast cell line, we could identify the origin of each protein based on variance between human and mouse proteins. Several families of proteins were identified, such as RNA-binding proteins, kinases, phosphatases, and secretory and endocytic proteins. Our data allows us to postulate that Cd81-exosome processing involves the use of the cancer cell endocytic and secretory pathways. By determining the mechanism whereby breast cancer cells use Cd81-exosomes as signals, it may be possible to block this process and prevent or slow metastatic events.
Citation Format: Ainsley Q. Underhill, Yingyi Amy Zhang, Liang Zhang, Valbona Luga, Jeff Wrana. Proteomic dynamics of stromal exosomes during processing in 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 B62.
Abstract C07: Impact of human epidermal-growth-factor receptor-2 (HER2) expression and two BRCA1/2 pathogenic mutations with outcome of the breast cancer patients
Authors: Fiuji Hamid , Bibak Bahram , Maftouh Mina , Mirhafez Reza , Avan Amir 
Published: August 2014

Abstract
Background/Aim: Breast cancer is a major unsolved health problem with poor prognosis; thus, identification of prognostic biomarkers is warranted. The aim of present study was to 1) evaluate the prevalence of the common mutations in the BRCA1 (C61G) and BRCA2 (6174delT) genes in Iranian patients with breast cancer, 2) and to investigate the correlation of these mutation and also HER-2, P53 and Ki67 expression with clinical outcome of the patients treated with standard regimen chemotherapy.
Patients and methods: 168 patients, including eighty healthy volunteers, were selected for BRCA1/2 mutation screening. DNA was isolated from blood samples and then frequency of 6174delT and C61G were evaluated in the patients using amplication refractory mutation system (ARMS) PCR and also by sequencing of the related site of genes in positive patients. Expressions of HER2, P53 and Pi27 were evaluated by ELISA, and their correlations with clinical outcome were investigated. We also analyzed data on overall survival according to clinicopathological characteristics of the patients.
Results: Consistent with previous findings, our analysis resulted in the identification of concomitant germline BRCA1 and BRCA2 mutations in none of the patients. Moreover, the present of the mutations were explored and confirmed by sequencing analysis of the positive and control samples, as well as in none of the patient samples. Furthermore, high expression of HER-2 and Ki67 were found in 42 and 66% of the patients, respectively, and were associated with significantly shorter OS. HER2 expression was associated with risk of death (e.g., hazard ratio= 1.6; 95%CI, 1.1–2.3, P&lt;0.05).
Conclusions: our results suggest that Iranian breast cancer patients represent the presence of additional kinds of BRCA1/2 alteration (such as genomic rearrangements/deletion) or by mutations on/different breast cancer related genes. However, ethnic background can also influence on prevalence of the mutations. These results prompt further studies as well as research on the biological role of these mutations in breast cancer. Nevertheless, larger multicenter studies are critical to explore the role of emerging biomarkers before planning of prospective trials.
Note: This abstract was not presented at the conference.
Citation Format: Hamid Fiuji, Bahram Bibak, Mina Maftouh, Reza Mirhafez, Amir Avan. Impact of human epidermal-growth-factor receptor-2 (HER2) expression and two BRCA1/2 pathogenic mutations with outcome of the breast cancer patients. [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 C07.
Abstract C53: rVP1 inhibits prostate cancer metastasis via suppression of Jagged1
Authors: Wang Jui-Ling , Hung Shao-Wen , Liang Chi-Ming , Hsiao Pei-Wen , Liang Shu-Mei 
Published: August 2014

Abstract
Jagged1, a NOTCH ligand, has been shown to correlate with poor prognosis and metastasis of prostate cancer (CaP). CaP is a leading cause of cancer death among men worldwide. There is currently no effective therapeutic strategy for patients with castration-resistant prostate cancer (CRPC) which is defined as continued growth of CaP despite the suppression of male hormones. We previously reported that recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus causes cell apoptosis of PC-3, a CRPC, via integrin β1 in vitro. Herein, we demonstrate that rVP1 inhibited cell migration/invasion at a non-toxic concentration and reduced the expression level of Jagged1 and phosphorylation of Akt (Ser 473) and IKKα/β (Ser 176/180) of PC-3 cells in vitro. This inhibition was abolished by integrin β1 blocking antibody, knockdown of integrin β1, or a constitutively active Akt. Furthermore, intravenous administration of rVP1 induced tumor apoptosis, suppressed tumor Jagged1 expression level, reduced primary-tumor spread to lymph nodes and bone, and prolonged the survival time of tumor-bearing mice in an orthotopic PC-3 xenograft model. Recombinant VP1 retarded tumor expansion within the bone and tumor-induced osteolysis in an experimental model of bone metastasis made by injecting PC-3 cells carrying the luciferase gene into mouse left ventricle. Finally, in vivo vascular permeability analyses showed that rVP1 specifically targeted tumor cells by penetrating leaky tumor vasculature. Recombinant VP1 may thus suppress Jagged1 expression of CaP cells by inhibiting the integrin β1/Akt/NF-κB signaling pathway to attenuate expansion of bone metastases and tumor-induced osteolysis in CRPC.
Citation Format: Jui-Ling Wang, Shao-Wen Hung, Chi-Ming Liang, Pei-Wen Hsiao, Shu-Mei Liang. rVP1 inhibits prostate cancer metastasis via suppression of Jagged1. [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 C53.