bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3424: Slug-mediated epithelial mesenchymal transition in lung cancer cells
Authors: Daisuke Tamura , Arao Tokuzo , Nagai Tomoyuki , Furuta Kazuyuki , Sakai Kazuko , Kudo Kanae , Kaneda Hiroyasu , Aomatsu Keiichi , Fujita Yoshihiko , Matsumoto Kazuko , Kotani Yoshikazu , Nishimura Yoshihiro , Saijo Nagahiro , Nishio Kazuto 
Published: June 2012

Abstract
Epithelial-Mesenchymal Transition (EMT) has been classified as a unique process by which epithelial cells undergo mesenchymal phenotype leading to increased motility and invasion. The aim of this study was to elucidate the biological functions of Slug/Snail2 in lung cancer cells.
We introduced Slug gene into several lung cancer cell line (A549, Ma1, and H1299) and established stable cell lines. Overexpression of Slug clearly mediated the EMT-related morphological changes including the cell scattering and the elongation of cell-shape. Real-time RT PCR and Western blot demonstrated that overexpression of Slug markedly downregulated the mRNA levels and protein levels of E-cadherin, while mesenchymal marker, N-cadherin, fibronectin 1 and vimentin, were upregulated. In addition to these changes, Slug enhanced the cellular migration activity and the cellular anchorage independent growth activity.
Finally, we examined the Slug-mediated EMT on drug sensitivity to several anti-cancer dugs. Interestingly, Slug-overexpressing cells increased the drug sensitivity to only tubulin-binding agents such as vinorelbine, vincristine, and paclitaxel in vitro. Microarray analysis revealed that Slug downregulates tubulin beta 3 or 4 expression. Luciferase promoter assay showed that Slug directly down-regulates tubulin beta 4 expression at the transcription level. These results suggested that Slug-mediated sensitivity to tubulin-binding agents may be involved in expression changes of tubulin beta 3 or 4.In conclusion, we found that overexpression of Slug mediates EMT and change of drug sensitivity to tubulin-binding agents, presumably via downregulations of tubulin beta 3 and 4 in lung cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3424. doi:10.1158/1538-7445.AM2011-3424
Abstract 3426: A signature for epithelial to mesenchymal transition in lung adenocarcinoma
Authors: Schliekelman Mark , Taguchi Ayumu , Wang Hong , Zhang Qing , Wong Chee-Hong , Chin Alice , Gazdar Adi , Hanash Samir 
Published: June 2012

Abstract
Identification of a molecular signature associated with epithelial to mesenchymal transition (EMT) may provide insight into the potential of a tumor to metastasize. To this effect we have undertaken a systems approach to understanding EMT with transcript and proteomic profiling of 30 lung adenocarcinoma cell lines. In-depth proteomic profiling was performed on conditioned media, cell surface and whole cell lysates from lung adenocarcinoma cell lines, allowing characterization as epithelial or mesenchymal based on their levels of E-cadherin and Vimentin, as well as cell morphology. Gene and protein expression from five cell lines that exhibited mesenchymal features were compared with five cell lines that exhibited epithelial features to identify proteins specifically associated with either a mesenchymal or epithelial phenotype. We identified protein signatures specific for mesenchymal or epithelial cells in the whole cell lysates, cell surface and conditioned media, with secreted proteins in the conditioned media representing the most distinct signature based on cluster analysis of protein expression. A much larger number of proteins were specific for epithelial cells than for mesenchymal, suggesting tighter regulation of expression in the epithelial cells. Networks of proteins associated with cell motion, extracellular matrix and growth regulation were identified that were distinct for mesenchymal cell lines while epithelial cell lines exhibited networks of proteins associated with metabolism and cell adhesion. Gene expression analysis of these cell lines supports the observations of tighter gene regulation in epithelial cells as well as the identified protein networks. Identification of a protein signature for EMT provides further understanding of a critical step in tumor progression and has the potential to yield biomarkers to assess likelihood of tumor metastasis in lung adenocarcinoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3426. doi:10.1158/1538-7445.AM2011-3426
Abstract 3428: Coordinated regulation of mesenchymal epithelial transition in the PMC42-LA breast cancer cell line variant
Authors: Hugo Honor J. , van Denderen Bryce JW , Tomaskovic-Crook Eva , Blick Tony , Huang Dexing , Pinto Cletus , Soo Eliza , Fabra-Fres Angels , Haviv Izhak , Goodall Greg , Wong Nicholas , Ackland Leigh , Newgreen Don F. , Waltham Mark , Thompson Erik W. 
Published: June 2012

Abstract
PMC42 cells were derived from a breast cancer pleural effusion and exhibit stem cell-like features when first characterized (Whitehead, Bertoncello et al. 1983; Whitehead, Monaghan et al. 1983). The PMC42-LA subline (Ackland, Michalczyk et al. 2001; Ackland, Newgreen et al. 2003) is distinctly less mesenchymal than parental PMC42-ET cells, but both exhibit EGF- and TGFβ-inducible mesenchymal-like change. Together they provide an ideal model in which to study the regulation of epithelial-mesenchymal plasticity in a breast cancer context. We have assessed in vitro parameters including migration, 3D colony formation and EMT marker expression, and undertook both miRNA profiling (mirVana probe set V1, Ambion) and alternative splice usage (Affymetrix human 1.0 ST whole genome exon arrays) analysis. Several miRNAs were expressed differently in the two sublines and/or up- or down-regulated in response to EMT-inducing treatments. Relative to the mesenchymal ET subline, the, miR-200 family members were elevated in the epithelial LA subline, where a corresponding loss of Zeb1 expression was seen. The LA subline also showed reduced E-Cadherin promoter methylation, and increased methylation of the Zeb1 promoter. Manipulation of the miR 200 family affected the EMT marker expression in these cells, as did Zeb1 suppression with shRNA. Matrigel invasion was also inhibited with Zeb1 knockdown. Additional gene expression changes and alternative splice usage, promoter methylation changes, and miR expression changes are under study. These studies may identify molecules and pathways that are important in cell specification across the epithelial mesenchymal axis, and represent diagnostic and therapeutic targets in breast cancer.
Ackland, M. L., A. Michalczyk, et al. (2001). “PMC42, A novel model for the differentiated human breast.” Exp Cell Res 263(1): 14-22.
Ackland, M. L., D. F. Newgreen, et al. (2003). “Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells.” Lab Invest 83(3): 435-48.
Whitehead, R. H., I. Bertoncello, et al. (1983). “A new human breast carcinoma cell line (PMC42) with stem cell characteristics. I. Morphologic characterization.” J Natl Cancer Inst 70(4): 649-61.
Whitehead, R. H., P. Monaghan, et al. (1983). “A new human breast carcinoma cell line (PMC42) with stem cell characteristics. II. Characterization of cells growing as organoids.” J Natl Cancer Inst 71(6): 1193-203.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3428. doi:10.1158/1538-7445.AM2011-3428
Abstract 3430: Snail1 regulates invasion through uPA-uPAR signaling in prostate cancer
Authors: Randle Diandra D. , Odero-Marah Valerie 
Published: June 2012

Abstract
PURPOSE: Epithelial-mesenchymal transition (EMT) is a process by which cancer cells acquire mesenchymal properties, such as induction of N-cadherin, while epithelial-associated genes like E-cadherin are lost. This enables the cells to be more invasive, migratory and metastatic. Factors that can induce EMT include growth factors like transforming growth factor -β (TGF-β) and epidermal growth factor (EGF), and transcription factors like Snail1. Snail1-induced EMT promotes migration and invasion and we hypothesized that this may be mediated by urokinase (uPA) and its receptor (uPAR) activities. uPA, a serine protease, may be activated by integrin engagement to bind to its receptor, uPAR, and initiate a signaling cascade that regulates a variety of biological pathways including migration and invasion. DESIGN METHODS: 22Rv1, LNCaP and ARCaP human prostate cancer (PC) cells were stably transfected with empty vector control (Neo) or constitutively active Snail which led to increased cell migration and invasion. The levels of Snail, uPA, and uPAR were measured by Western Blot analysis. uPA activity in conditioned media was measured using the Elisa uPA activity assay kit. Also, cells were treated with PI3K and MAPK inhibitors at set time points. RESULTS: The data suggests that overexpression of Snail1 increased uPA and uPAR protein levels, while uPA activity was elevated in conditioned media from ARCaP, LNCaP and 22Rv1 cells transfected with Snail. In addition, MAPK inhibitor, UO126, inhibited ERK activity within 30 min up to 72 h, and decreased uPA activity within 24 h. CONCLUSION: Therefore, Snail-mediated cell migration and invasion in human prostate cancer cells may occur via the regulation of uPA/uPAR and MAPK activities.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3430. doi:10.1158/1538-7445.AM2011-3430
Abstract 3431: Regulation of integrins AlphaV Beta3 and focal adhesion kinase signaling by PTTG in induction of EMT
Authors: Shah Parag P. , Kakar Sham S. 
Published: June 2012

Abstract
Pituitary tumor transforming gene (PTTG) is a well-studied oncogene for its role in tumorigenesis. PTTG expression levels correlate with the tumor development, growth and metastasis and serve as a marker of malignancy in several cancer types including lung. Epithelial to mesenchymal transition (EMT) is a crucial step in tumor progression and metastasis, during which epithelial cells lose their polarity and cell-cell adhesion. Integrins are transmembrane proteins which bind ligands found in the extracellular matrix. Interactions between the extracellular matrix and the actin cytoskeleton commonly take place at focal adhesions on the cell surface that contain localized concentrations of integrins, signaling molecules, and cytoskeletal elements. Talin forms a direct interaction with the integrin cytoplasmic domain, and interacts with cytoskeletal elements (actin) and signaling factors. The present study was focused to define the regulation of integrins and FAK pathway by PTTG in induction of EMT. For our studies, we used lung cancer cell lines A549 and H1299 and infected with adenovirus expressing PTTG cDNA or adenovirus expressing control GFP. Using Real Time PCR and immunohistochemistry and FACS analysis, we observed that overexpression of PTTG in cells resulted in a significant increase in the expression of integrins αv and β3 in both cell lines compared to uninfected cells or cells infected with adenovirus expressing GFP. These results were confirmed by the down-regulation of PTTG expression using adenovirus expressing PTTG-specific siRNA that showed a significant decrease in the expression of integrins αv and β3. Western blot analysis revealed increased phosphorylation of FAK on overexpression of PTTG. Analysis of downstream signaling genes such as Paxillin, Metavinculin and Rac 1 by quantitative real time PCR analysis showed positive correlation between levels of PTTG and these genes. Treatment of A549 and H1299 cells with the αvβ3 antagonist echistatin (RGD peptide) and siRNA specific for integrin αv resulted in a decreased in phosphorylation of FAK as well as expression of downstream signaling genes Paxillin, Metavinculin and Rac 1. The Vinculin and Phallodoin are responsible for the functional link of FAK to the actin cytoskeleton. Disruption of actin cytoskeleton was confirmed with immunostaining. Taken together our results suggest for the first time an important role of PTTG in regulation of integrins αv and β3 leading to change in Focal Adhesion Kinase (FAK) pathway resulting in induction of EMT.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3431. doi:10.1158/1538-7445.AM2011-3431
Abstract 3434: Thromboxane a2 receptor beta is induced by the epithelial to mesenchymal transition of breast cancer cells and contributes to breast cancer motility and metastasis
Authors: Zhang Xuejing 
Published: June 2012

Abstract
Previous studies in our lab showed that thromboxane a2 receptor (TP) activation has profound effect on tumor cell cytoskeleton and contraction through activation of RhoA and depletion of TP reduces the metastatic dissemination of breast cancer cells in vivo. We report here that TP-beta expression is induced during epithelial-mesenchymal transition (EMT) and its activation is required for efficient migration and invasion of breast cancer cells. Elevated TP-beta expression is found associated with metastasis in tissues obtained from breast cancer patients. Breast cancer cell lines with high TP-beta expression present more malignant phenotype than the cells with low or no TP-beta expression. It is known that TP-alpha and TP-beta expressions are under the control of different promoter P1 and P3, respectively. Downregulation of E-cadherin in immortalized human mammary epithelial cells (Rao1) and breast cancer cells (MCF7) induces morphological changes of the cells to the mesenchymal type and upregulation of transcription factors that regulate EMT. Interestingly, TP-beta expression and P3 promoter activity are increased in the E-cadherin knock down cells, in contrast the level of TP-alpha remains unchanged. Further, beta-catenin/Tcf/LEF complexes are found to bind to and activate P3 promoter. Finally, a TP-beta specific inhibitor CAY10535 blocks the increased migration/invasion ability of MCF7 cells that is triggered during EMT. Together, these results indicate that beta-catenin released from membrane E-cadherin binding during EMT stimulates TP-beta expression by activating P3 promoter activity together with Tcf/LEF complexes and TP-beta activation enables enhanced migratory capacity, invasiveness of breast cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3434. doi:10.1158/1538-7445.AM2011-3434
Abstract 3437: Epithelial-mesenchymal transition spectrum characterized by an ovarian cancer cell line library defines an aggressive metastable state
Authors: Huang Ruby YJ , Wong Meng Kang , Chung Vin Yee , Ng Aloysius , Lee You Fei , Pietschmann Elke , Mori Seiichi , Matsumura Noriomi , Thiery Jean Paul 
Published: June 2012

Abstract
Epithelial-mesenchymal transition (EMT) has been implicated to be one of the driving mechanisms of carcinoma progression in many solid tumours, such as breast, colorectal, and ovarian cancer. It explains how carcinoma cells invade and metastasize by transforming an epithelial state via a metastable state to a mesenchymal state. Many studies have addressed the epithelial and mesenchymal states. However, understanding of the metastable state is still limited. In this study, we describe a model system for appraising the spectrum of EMT by using 42 well-characterized ovarian cancer cell lines. Phenotypic EMT characterization reveals 4 subgroups which represent different epithelial-mesenchymal compositions on the EMT spectrum. Genome-wide transcriptional characteristics and recurrent genomic alterations specific for each subgroup are also described. We also demonstrate that this EMT spectrum can be used to refine the analysis of data generated in cell-based functional studies. Ovarian cancer cells harbouring intermediate phenotypes are more migratory, invasive, anoikis resistant, and more spheroidogenic. This ovarian cancer cell line EMT spectrum allows fine tuning of the EMT process by further characterizing the metastable state, which can help reduce heterogeneity. Several candidate genes were applied in a human ovarian carcinoma collection to determine the EMT status by using methods such as quantitative PCR. We conclude that this EMT spectrum library can contribute to the identification of molecular features that serve as predictive diagnostic markers or therapeutic targets associated with EMT.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3437. doi:10.1158/1538-7445.AM2011-3437
Abstract 3438: Oncogenes-induced interferon-beta: modulation of tranformation phenotypes through interferon-ISG15 autocrine signaling
Authors: Tsai Yu-Chen , Pestka Sidney , Wang Lu-Hai , Runnels Loren W. , Liu Leroy F. 
Published: June 2012

Abstract
ISG15 (interferon-stimulated gene 15), an ubiquitin-like protein (UBL), is a new tumor marker whose expression has been correlated with disease progression in bladder cancer and suggested to be prognostic for breast cancer. However, the molecular basis for, and the function of, ISG15 overexpression in tumors remain unclear. Here, we show that ISG15 overexpression in both breast cancer cells and oncogenic Ras-transformed mammary epithelial cells (MCF-10A) is due to elevated secretion of interferon-β. Moreover, interferon-β-ISG15 autocrine signaling in oncogenic Ras-transformed MCF-10A cells results in increased colony formation efficiency. Interestingly, gain of epithelial-mesenchymal transition (EMT) characteristics, including appearance of spindle-shaped cell morphology and EMT markers, as well as increased cell migration, in Ras-transformed MCF-10A cells is also dependent on interferon-β-ISG15 autocrine signaling. Our results demonstrate for the first time that tumor cell-secreted interferon-β may modulate tumor cell growth and migration through ISG15, suggesting potential cancer therapeutic approaches by antagonizing interferon autocrine signaling.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3438. doi:10.1158/1538-7445.AM2011-3438
Abstract 3441: Cross-species expression profiling identifies Forkhead-Box Q1 as a promoter of epithelial-mesenchymal transition and breast cancer metastasis
Authors: Zhang Haijun , Meng Fanyan , Liu Gang , Zhang Bin , Zhu Jun , Wu Feng , Ethier Stephen P. , Miller Fred , Wu Guojun 
Published: June 2012

Abstract
Utilizing a cross-species expression profiling strategy that combines microarray techniques and metastatic cell lines of human and mouse origins, 22 up-regulated and 12 down-regulated genes were identified as an essential genetic program in highly-metastatic cell lines. The correlation of all gene expression levels and metastasis potential was confirmed by RT-PCR in a set of human and mouse cancer cells. Among these genes, Forkhead-Box Q1 (Foxq1) is a transcription factor with a function in metastasis that has not yet been reported upon. We showed that ectopic expression of Foxq1 increased cell migration and invasion in vitro; significantly enhanced lung metastatic capabilities of mammary epithelial cells in vivo and resulted in a marked epithelial to mesenchymal transition (EMT). In contrast, knockdown of Foxq1 expression led to the opposite change in vitro and in vivo. Neither ectopic expression nor knockdown of Foxq1 had significant effects in cell proliferation and colony formation in vitro. Additionally, we showed that Foxq1 repressed E-cadherin expression by binding to the E-box in its promoter region. Finally, we found that the expression of Foxq1 is regulated by TGF-β1, and that knockdown of Foxq1 blocked EMT induced by TGF-β1 treatment at morphological and molecular levels. Our study highlights the feasibility of cross-species expression profiling as a strategy in identifying metastasis-related genes. It also reveals that the inducement of EMT is a potential mechanism for the novel metastasis-promoting function of Foxq1 in breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3441. doi:10.1158/1538-7445.AM2011-3441
Abstract 3451: Interactions between N-myc and Sox9 promote medulloblastoma and determine cell fate decisions in cerebellar neural stem cells
Authors: Swartling Fredrik J. , Persson Anders I. , Lau Jasmine , Northcott Paul A. , Grimmer Matthew R. , Chesler Louis , Perry Arie , Phillips Joanna J. , Taylor Michael D. , Weiss William A. 
Published: June 2012

Abstract
The proto-oncogene MYCN (N-myc in mice) regulates normal brain development, and is often misexpressed in childhood brain tumors, including medulloblastoma. While most medulloblastoma arise independently of Sonic hedgehog (Shh), about ∼25% of are Shh-dependent and have a more favorable prognosis. We recently induced Shh-independent classic and large cell anaplastic medulloblastoma by driving MYCN from the glial Glutamate Transporter 1 promoter in a tet-regulated transgenic mouse model (Swartling et al, 2010). To characterize cell of origin, we used BrdU labeling in premalignant transgenic mice, demonstrating increased proliferation in cerebellar Bergmann glial cells. Bergmann glia showed high levels of glial marker GFAP as well as the transcription factor Sox9. Whereas neural stem cells (NSCs) from normal perinatal cerebellum contained a high proportion of Sox9-positive cells, primary cultures of tumor spheres showed low levels of Sox9, suggesting that MYCN suppresses Sox9 during medulloblastoma progression. To clarify mechanism, we transduced wild-type (WT) or mutationally-stabilized N-myc-T58A into GFAP-positive NSCs from perinatal murine cerebellum. Transplantation of N-myc-WT NSCs was insufficient for tumor formation. N-myc-T58A cerebellar NSCs generated both Shh-dependent and Shh-independent medulloblastoma, as a function of prenatal or postnatal cerebellar age, respectively. Expression of Sox9 correlated directly with Sonic Hedgehog (Shh) dependence in both murine and human medulloblastoma samples. In addition, forced expression of Sox9 induced Shh-dependence and self-renewal in the Shh-negative mouse medulloblastoma spheres. Our data suggest 1). A glial cell of origin for MYCN-driven medulloblastoma, and 2). Sox9 as a critical target for MYCN during medulloblastoma initiation, with activation of Sox9 leading to Shh-dependence, and inhibition of Sox9 leading to Shh-independent medulloblastoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3451. doi:10.1158/1538-7445.AM2011-3451