bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 207: Caveolin-1 drives oncogenic TGFβ effects in prostate cancer: in vitro mechanistic insights integrated with systems pathology visualization in primary tumor samples
Authors: Pellinen Teijo , Blom Sami , Sanches Sara , Välimäki Katja , Mpindi John-Patrick , Rannikko Antti , Strippoli Raffaele , Montoya Maria , Azegrouz Hind , Mirtti Tuomas , del Pozo Miguel , Kallioniemi Olli 
Published: August 2015

Abstract
Caveolin-1 (Cav1) can have both a tumor suppressive or promoting role depending on cancer tissue, and its potential active role in the progression of prostate cancer remains poorly understood. In this study, we found out that Cav1 represses the expression of E-cadherin in prostate cancer cell lines, and that the expressions of these two genes show an inverse correlation both at the mRNA and protein levels in PCa patient samples. We show that the combined loss of E-cadherin and gain of Cav1 expression is an early event in a subgroup of patients (&lt;10%) (n(patients) = 80, n(glands) = 263, r = -0.35, p&lt;0.001). Cav1 positively regulates TGFβ targets with known oncogenic and pro-EMT functions (e.g. Slug, Pai-1), and its absence switches the TGFβ to become inhibitory to PCa cells by inducing p21 (CDKN1A) and STAT1 signaling. These changes were strongly associated with changes in 3D-invasive growth. By using RNAi image-based screening, we found out that Cav1 is positively regulated by beta1-integrins and cell adhesion to ECM. This association together with different alpha-integrins was visualized and quantified in human prostate cancer patient tissues (n = 80) using novel multiplexed fluorescent imaging. Both the integrin beta1 and alpha2 showed high correlation with Cav1 expression (p-values&lt;0.001) in tumor epithelium as well as in stroma.
In conclusion, the results suggest that Cav1 could be an important promoter of invasive growth in a subgroup of PCa, where it is upregulated by beta1-integrins, and where it promotes oncogenic TGFβ signaling.
Citation Format: Teijo Pellinen, Sami Blom, Sara Sanches, Katja Välimäki, John-Patrick Mpindi, Antti Rannikko, Raffaele Strippoli, Maria Montoya, Hind Azegrouz, Tuomas Mirtti, Miguel del Pozo, Olli Kallioniemi. Caveolin-1 drives oncogenic TGFβ effects in prostate cancer: in vitro mechanistic insights integrated with systems pathology visualization in primary tumor samples. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 207. doi:10.1158/1538-7445.AM2015-207
Abstract 2070: Stxbp4 suppresses APC/C mediated turnover of p63 and increases tumorigenicity and malignancy
Authors: Otaka Yukihiro , Rokudai Susumu , Kaira Kyoichi , Shimizu Kimihiro , Ito Masashi , Ichihara Ami , Kawabata Reika , Yoshiyama Shinji , Yamane Arito , Asao Takayuki , Prives Carol , Nishiyama Masahiko 
Published: August 2015

Abstract
p63 plays a pivotal role in epithelial development and maintenance of epithelial proliferative potential. The delN isoforms of p63 are thought to be involved in both basal-epidermal gene expression and maintenance of epithelial progenitor proliferative potential. It is also thought that delN versions of p63 and p73 can serve to inhibit the abilities of their TA isoform counterparts to induce cell cycle arrest and apoptosis. Consistent with this, after DNA damage or during terminal differentiation, delNp63 proteins are quickly down regulated. Although p53 is frequently mutated in human cancers, p63 mutation is rare and it overexpresses especially in squamous carcinomas, such as lung, bladder, breast, and head and neck squamous cell carcinoma. Indeed several report concluded that immuno histochemistry with delNp63 is a powerful ancillary method for classifying lung adenocarcinoma and squamous carcinoma, a distinction with important therapeutic implications. We previously reported that APC/C plays a role in ubiquitin-mediated turnover of delNp63 and that Stxbp4 suppresses the degradation of delNp63 by the APC/C and Rack1-VHL. Importantly, both Stxbp4 and APC/C degradation-resistant delNp63 suppress the terminal differentiation process in 3D organotypic culture model as well as in vitro culture. To investigate the effect and the mechanism of delNp63 for tumorigenicity and malignancy in Lung squamous carcinoma, we examined a transcriptome analysis (RNA-seq) of delNp63 and Stxbp4 with NGS (Next Generation Sequencer) and generated xenograft mice model. Thus, our study provides insight into a novel mechanism for delNp63 in regulating tumorigenicity and malignancy in squamous cell carcinoma as well as epitherial development.
Citation Format: Yukihiro Otaka, Susumu Rokudai, Kyoichi Kaira, Kimihiro Shimizu, Masashi Ito, Ami Ichihara, Reika Kawabata, Shinji Yoshiyama, Arito Yamane, Takayuki Asao, Carol Prives, Masahiko Nishiyama. Stxbp4 suppresses APC/C mediated turnover of p63 and increases tumorigenicity and malignancy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2070. doi:10.1158/1538-7445.AM2015-2070
Abstract 2086: Role of the transcription factor NFE2L3 in TNFα signaling pathway in colorectal cancer
Authors: Bury Marina , Blank Volker 
Published: August 2015

Abstract
Patients with inflammatory bowel disease have an increased risk of developing colorectal cancer (CRC), which is the third leading cause of cancer related deaths in the world. Our laboratory is studying the transcription factor NFE2L3 [nuclear factor (erythroid-derived 2)-like 3]. NFE2L3, a member of the Cap’n’Collar family, is a basic-region leucine zipper transcription factor that was identified 15 years ago. Contrary to its extensively studied homolog NFE2L2, the role of NFE2L3 in cancer is still unknown. We demonstrated that NFE2L3 functions as heterodimer by complexing with small Maf (musculoaponeurotic fibrosarcoma) proteins for DNA binding. According to the clinical databases, NFE2L3 is up-regulated in CRC compared to normal tissues. Using the colorimetric MTT viability assay, we determined the optimal concentration to treat colon cell lines with the tumor necrosis factor-alpha (TNFα), a pro-inflammatory cytokine associated with CRC tumorigenesis. We showed that protein levels of NFE2L3 and small Maf proteins are up-regulated by TNFα in CRC cells. We used genomic approaches for identifying genes that are modulated by NFE2L3 after TNFα treatments. The identification of the precise role of NFE2L3 in TNFα signaling pathway will lead to a better understanding of colorectal cancers and will help in the design of novel treatment options.
Citation Format: Marina Bury, Volker Blank. Role of the transcription factor NFE2L3 in TNFα signaling pathway in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2086. doi:10.1158/1538-7445.AM2015-2086
Abstract 2119: Identification of a RNA binding protein, SSP1, inducing cell growth in esophageal squamous cell carcinoma (ESCC)through posttranscriptional regulation of target genes
Authors: Imoto Issei , Masuda Kiyoshi , Shoda Katsutoshi , Hamada Jyunichi 
Published: August 2015

Abstract
RNA-binding proteins (RBPs) involve in many post-transcriptional aspects of RNA metabolism. Although the impact of RBPs on expression of cancer-associated genes is well recognized, their crucial functions in carcinogenesis remain unclear. Here we show that a RBP, squamous cell carcinoma-specific protein 1 (SSP1, Lab name), promotes the cell growth in esophageal squamous cell carcinoma (ESCC) through regulating the expression of cell cycle- and apoptosis-associated genes. Immunohistochemical analysis of dissected ESCC samples showed that SSP1 was highly expressed in advanced ESCC compared with normal tissues. Expression levels of SSP1 was positively and significantly correlated with tumor size, invasion depth and overall survival of patients with ESCC. The correlation between SSP1 expression level and overall survival was significant even after stratified with other clinicopathological factors, indicating SSP1 to be an independent prognosticator in ESCC. Knockdown of SSP1 inhibited cell growth and induced G0/G1 arrest in ESCC cell lines, whereas stably overexpressed SSP1 promote cell growth. Ribonucleoprotein immunoprecipitation analysis followed by RNA sequencing (RIP-seq) revealed that SSP1 bound to large sets of mRNAs, including TP53, RB1, CCNA2, CCND1, BAX, and FAS, and regulated their expression through regulation their translation. Our results indicated SSP1 might be one of the crucial molecular targets for ESSC.
Citation Format: Issei Imoto, Kiyoshi Masuda, Katsutoshi Shoda, Jyunichi Hamada. Identification of a RNA binding protein, SSP1, inducing cell growth in esophageal squamous cell carcinoma (ESCC)through posttranscriptional regulation of target genes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2119. doi:10.1158/1538-7445.AM2015-2119
Abstract 2120: Not all ribosomes are created equal: How cancer abuses the translational machinery
Authors: Landon Ari L. , Muniandy Parameswary , Gartenhaus Ronald B. 
Published: August 2015

Abstract
Translational Dysregulation is emerging as a prominent mechanism leading to the malignant phenotype. These changes in protein levels can lead to cancer initiation, maintenance and progression. Cap-dependent translation is the primary mechanism of mRNA translation in eukaryotic cells. Cap-dependent translation is initiated by eIF4E1 binding to the 7-methyl-guanosine-cap (cap). The conventional translation initiation complex eIF4F consists of eIF4A, eIF4G and eIF4E. eIF4E binds the cap structure in the mRNA functioning as a bridge between mRNA and the ribosome. MNK kinases are responsible for phosphorylating eIF4E1. We observed that knocking down MNK kinases translationally represses total eIF4E1 expression. Interestingly, MNK down regulating total eIF4E1 occurs specifically in B-cells. This novel impact on total eIF4E1 demonstrates the potential for MNK1 and MNK2 to directly impact a large subset of oncogenes in a B-cell specific manner. Inhibiting MNK kinase activity and subsequent eIF4E1 phosphorylation results in an increase in eIF4E3 protein expression. eIF4E3 is another member of the eIF4E family that has been shown to bind the cap by an atypical mechanism. We explored the biological function of eIF4E3 in a diffuse large B-cell lymphoma model. The increase in total eIF4E3 competes with eIF4E1 for binding to the cap. We found that eIF4E3 also physically associates with eIF4A and eIF4G forming a novel eIF4F complex. We interrogated the functional aspects of eIF4E3-mediated translation by analyzing the translatome and transcriptome of eIF4E3 expressing cells. eIF4E3 and eIF4E1 mutually regulate a high fraction of total mRNA transcripts while both family members exclusively modulate translation of select messages. We identified selective motif enrichments in the 5′UTR that may facilitate transcript selection by eIF4E1 or eIF4E3. These findings imply alternative ribosomal complexes that are able to selectively translate mRNA via transcript recognition. The dual roles of MNK proteins for both eIF4E1 phosphorylation and total expression highlight MNK as a powerful oncogenic translation switch.
Citation Format: Ari L. Landon, Parameswary Muniandy, Ronald B. Gartenhaus. Not all ribosomes are created equal: How cancer abuses the translational machinery. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2120. doi:10.1158/1538-7445.AM2015-2120
Abstract 2123: Protein synthesis and its control in cancer development, progression and treatment
Authors: Parsyan Armen 
Published: August 2015

Abstract
A central dogma of molecular biology posits that the protein biosynthetic pathway generally follows the three major events: replication, transcription and translation. The abnormal functioning of any of these processes can nurture malignant cellular transformation. While other components of the central dogma were front-page in cancer research, translation, somewhat, remained in the shades. This presentation is based on the recently published book “Translation and Its Regulation in Cancer Biology and Medicine”* that for the first time comprehensively summarizes and analyzes decades of information into the role of the aberrations in protein synthesis, translation, as well as its regulation in the biology of cancer. The mechanisms of action of various translation factors, such as oncoprotein eIF4E, and tumor suppressors, such as PDCD4, are intensively discussed. Other, less-studied protein factors participating in the complex process of translation are presented in light of their known or emerging roles in cancer development and progression. In addition, the presentation focuses on the oncogenic role of the regulation of the translation machinery by fundamental cellular signal transduction pathways, such as mTOR, MAPK and others. Finally, clinical applications of the current knowledge regarding the translation machinery, its function and regulation in cancer are highlighted, including the use of the translation factors as diagnostic and prognostic markers, as well as factors for novel approaches to targeted pharmacologic treatment.
* Translation and Its Regulation in Cancer Biology and Medicine
Parsyan, Armen (Ed.)
2014, XXXIV, 697 p. 52 illus., 44 illus. in color., Hardcover
ISBN 978-94-017-9078-9
Springer Publishing
Website: http://www.springer.com/biomed/cancer/book/978-94-017-9077-2
Citation Format: Armen Parsyan. Protein synthesis and its control in cancer development, progression and treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2123. doi:10.1158/1538-7445.AM2015-2123
Abstract 2132: Mutant Kras associated protein oxidation in pancreatic neoplasia
Authors: Schultz Michelle , DeCant Brian , Diaz Andrew , Solman Sharon , Shah Rital , Bentrem David , Grippo Paul J. 
Published: August 2015

Abstract
Recent studies have suggested that mutant Kras associated activation of the Nrf2 pathway may have a significant role in pancreatic cancer (PaCa) tumorigenesis. Nrf2 regulates a battery of antioxidant genes, including peroxiredoxin-1 (Prdx-1), thioredoxin (Txn), and sulfiredoxin (Srxn), which are responsible for maintaining redox homeostasis in the cell. While ROS detoxification may have significant roles in cancer, several non-classical mechanisms of redox signaling associated with protein oxidation and phosphorylation are also important in tumorigenesis. Prdx-1 can regulate transcription as a cofactor in multiple oxidation states, represses tumorigenesis in its reduced state, and can act as a nuclear chaperone in elevated states of oxidation and when phosphorylated. Txn and Srxn prevent Prdx-1 overoxidation. We are therefore investigating the role of Prdx-1 oxidation and Txn and Srxn regulation in oncogenic signaling pathways in mutant Kras models of pancreatic tumorigenesis and neoplasia. Our data suggest that throughout tumor progression, Prdx-1 expression and localization are differentially regulated. These changes also correlated with reduced Txn and Srxn expression in lesions. In vitro, neoplastic and tumorigenic pancreatic cell lines have more total prdx-1 expression and oxidized Prdx-1 expression than non-tumorigenic cell lines. Moreover, cells that have mutant Kras were associated with higher levels of protein oxidation than those with wildtype Kras expression. Interestingly, mutant Kras was also associated with differences in pERK interaction with Prdx-1, which was also differentially regulated by NOX inhibitors and omega-3 fatty acids that control pancreatic neoplasia. ERK inhibitors also differentially affected Prdx1 expression in pancreatic cells in vitro. In addition, AKT, ERK, and FOXO3a phosphorylation were also modified by DPI treatment (NOX inhibitor) and omega-3 fatty acid treatment in wildtype and mutant Kras normal, neoplastic, and tumorigenic cell lines. We therefore conclude that mutant Kras is associated with elevated levels of Prdx-1 oxidation and that Kras-mediated activation of ERK could be associated with changes in Prdx-1 signaling in pancreatic neoplasia.
Citation Format: Michelle Schultz, Brian DeCant, Andrew Diaz, Sharon Solman, Rital Shah, David Bentrem, Paul J. Grippo. Mutant Kras associated protein oxidation in pancreatic neoplasia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2132. doi:10.1158/1538-7445.AM2015-2132
Abstract 2134: Standard immunohistochemistry efficiently screens for ALK rearrangements in differentiated thyroid cancer
Authors: Park Gahee , Kim Tae Hyuk , Lee Hae-Ock , Lim Jung Ah , Won Jae-Kyung , Min Hye Sook , Lee Kyu Eun , Park Do Joon , Park Young Joo , Park Woong-Yang 
Published: August 2015

Abstract
The anaplastic lymphoma kinase (ALK) gene is frequently rearranged in various types of cancer, and is highly responsive to the target therapeutics. We developed a pipeline to detect ALK rearrangement in a large group of Korean thyroid cancer patients. We screened 474 malignant or benign thyroid tumor cases to find ALK fusion. The expression and translocation of the ALK gene were analysed by immunohistochemistry (IHC), fluorescence in situ hybridisation (FISH), and digital multiplexed gene expression (DMGE) using formalin-fixed paraffin embedded tissues. Four cases of ALK rearrangement were screened out of 474 patients by IHC, which were validated by performing FISH for 189 samples. On the other hand, DMGE analysis using Nanostring could detect three out of four IHC positive cases. Two ALK rearrangements were Striatin (STRN)-ALK fusion, identified by 5′ RACE analysis. ALK rearrangements were found exclusively in the BRAF wild type papillary carcinoma. Given the wide availability and accuracy for detecting ectopic ALK expression in the thyroid, we suggest that IHC based screening can be used as a practical method for identifying patients with ALK rearranged differentiated thyroid cancer.
Citation Format: Gahee Park, Tae Hyuk Kim, Hae-Ock Lee, Jung Ah Lim, Jae-Kyung Won, Hye Sook Min, Kyu Eun Lee, Do Joon Park, Young Joo Park, Woong-Yang Park. Standard immunohistochemistry efficiently screens for ALK rearrangements in differentiated thyroid cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2134. doi:10.1158/1538-7445.AM2015-2134
Abstract 2135: Survivin is a novel target of the Hedgehog/GLI signaling pathway in human tumor cell lines
Authors: Vlčková Kateřina , Ondrušová Lubica , Réda Jiri , Vachtenheim Jiri , Záková Petra 
Published: August 2015

Abstract
Survivin, a pivotal antiapoptotic protein is expressed in tumors whereas its expression in normal tissues is extremely low. It is believed that transcription of the survivin gene is driven mainly by the transcription factor Sp1. We have identified 11 potential consensus sites for GLI trancription factors in the survivin promoter, albeit non of them has been a full consensus. Interestingly, the distal part of the promoter (-1765 to -941, ending at +39) containing 4 GLI sites showed about 2-fold higher activity than the proximal promoter (-941 to +39). The survivin promoter-reporter has been found to be upregulated mainly by plasmids encoding GLI2 and deltaN-GLI2, a more active GLI2 truncated mutant. Its activity was even higher than the Sp1 activity. The promoter-reporter plasmid is also inhibited by the GLI1/2 inhibitor GANT61. Moreover, by analyzing 40 human tumor cell lines of various origin, we have found that the endogenous survivin protein level substantially decreases after the incubation with GANT61 in most cell lines. Real-time PCR for the survivin mRNA in GANT61-sensitive cell lines showed a decrease by up to about 50 per cent. These data suggest that survivin may be a novel important target regulated by the Hedgehog/GLI signaling pathway, which has been reported previously to be deregulated in the majority of tumor types. The work was supported by the grant NT/14005 from IGA, Ministry of Health, Czech Republic.
Citation Format: Kateřina Vlčková, Lubica Ondrušová, Jiri Réda, Jiri Vachtenheim, Petra Záková. Survivin is a novel target of the Hedgehog/GLI signaling pathway in human tumor cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2135. doi:10.1158/1538-7445.AM2015-2135
Abstract 2146: RASSF1C modulation of Piwi-interacting RNAs (piRNAs) in lung cancer
Authors: Amaar Yousef G. , Firek Matthew , Reeves Mark E. , Reeves Mark E. 
Published: August 2015

Abstract
Introduction: RASSF1C is emerging as an important oncoprotein in lung cancer cell growth. We have shown that RASSF1C promotes lung cancer cell proliferation and migration; and RASSF1C up-regulates important genes in lung cancer cell growth that include a stem cell self-renewal gene, piwi1 (hiwi). PIWI-like proteins are a subfamily of Argonaute proteins that interact with small PIWI-interacting RNA molecules (known as piRNAs that are 24-32 nucleotides long) to form complexes that regulate transcriptional and translational repression. This leads to inhibition of apoptosis, stimulation of cell division and proliferation, and down-regulation of cyclin inhibitors and tumor suppressors. Therefore, modulation of Piwil1-piRNA gene expression by RASSF1C suggests a potential role for RASSF1C in lung cancer stem cell development and progression. To further investigate our hypothesis, we carried out a global piRNA microarray screen to identify piRNAs that are modulated by RASSF1C in lung cancer cells.
Method: A piRNA microarray screen was performed using the lung cancer cell line H1299 stably over-expressing RASSF1C (and controls). Total RNA was extracted from experimental and control cells and was submitted to Arraystar (Rockville, MD) for the piRNA microarray screen and data analysis.
Results: The piRNA microarray screen identified several piRNAs that are regulated by RASSF1C and we have confirmed the expression of some of them in cell lines. The function of the piRNAs identified is yet to be determined. We have initiated studies to determine the function of some of the most up-regulated and down-regulated piRNA genes in lung cancer cells. We are also profiling the expression of these piRNAs in normal and lung tumor tissues.
Conclusion: Several piRNAs are target genes of RASSF1C. Characterization of the function of these piRNAs may enhance our understanding of the role of RASSF1C in promoting lung cancer stem cell growth and progression. Linking a Rassf1c-Piwil1/piRNAs axis to lung cancer stem cell development and progression could possibly lead to discovery of new diagnostic and therapeutic targets for lung cancer.
Citation Format: Yousef G. Amaar, Matthew Firek, Mark E. Reeves, Mark E. Reeves. RASSF1C modulation of Piwi-interacting RNAs (piRNAs) in lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2146. doi:10.1158/1538-7445.AM2015-2146