bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3506: Heregulin induces transformation of mammary epithelial cells via HER3 activation
Authors: Lupu Ruth , Khurana Ashwani , Lugo Ghiara , Guerrico Anatilde Gonzalez 
Published: May 2015

Abstract
Heregulin (HRG)s are high-affinity combinatorial ligands for the HER family of tyrosine kinase receptors. HRG induces heterodimerization and cross-talk between members of the HER tyrosine kinase receptor family. HRG interaction with HER3 induces heterodimerization between HER3 and other HER receptors, including epidermal growth factor receptor (EGFR) and HER2, resulting in cross-talk-induced tyrosine phosphorylation. Several studies have revealed that HRG is expressed in about 40% of invasive breast carcinomas, many of which are triple negative breast carcinomas. We have previously demonstrated that HRG expression induces tumorigenesis and metastasis of MCF-7 cells. We tested the effect of HRG on non-committed MCF10A cells. MCF-10A cell line is an immortalized, non-transformed epithelial cell line derived from human fibrocystic mammary tissue. These cells lack the ability to form tumors in nude mice and the ability to grow in anchorage-independent assays. We found that forced expression of HRG in MCF10A induced cellular transformation, while the control MCF10A/Vector cells did not growth. MCF10A/HRG cells express constitutive phosphorylation of HER3 and induction of the signaling cascade. HER3 phosphorylation occurs as a result of HRG induction of HER3 heterodimerization with EGFR in an autocrine manner. Lapatinib, a dual tyrosine kinase inhibitor which interrupts the HER2 and EGFR pathways, blocked HER3 phosphorylation and the resulted signaling in MCF10A/HRG cells and prevented their anchorage-independent growth demonstrating that HER3 phosphorylation is responsible, at least in part, for the transformation of MCF10A/HRG cells. This study provides an alternate targeting prospective for breast carcinomas that express HER3 and HRG by targeting the autocrine-loop (HRG/HER3) and thus preventing HRG from binding to HER3, disrupting the possible receptor heterodimerization, and leading to blockage of the proliferative signals and promoting inhibition of growth.
Citation Format: Ruth Lupu, Ashwani Khurana, Ghiara Lugo, Anatilde Gonzalez Guerrico. Heregulin induces transformation of mammary epithelial cells via HER3 activation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3506. doi:10.1158/1538-7445.AM2014-3506
Abstract 351: Comparative studies on SIRT6 and SIRT7 interactomes: Implications of important roles in cancer via associating with interacting partners
Authors: Lee Namgyu , Kwon Jung-Hee , Park Sung Jin , Choi Kwan Yong 
Published: May 2015

Abstract
Sirtuins are NAD+-dependent deacetylases that regulate a range of cellular processes. Although anti-aging effects of sirtuins have been proposed, the proteins interacting with SIRT6 and SIRT7 remain elusive. In the current study, we identified SIRT6- and SIRT7-interacting proteins and compared their interactomes. Our data revealed 129 novel interacting proteins for SIRT6 and 122 for SIRT7 while confirming 7 and 111 previously identified proteins for SIRT6 and SIRT7, respectively. Comparison of the SIRT6 and SIRT7 interactomes under a same experimental condition disclosed 111 shared proteins indicated that functional associations. The functional networks of interactomes exhibited that the binding partners are associated with important biological processes in aging and age-related diseases including cancer. Two proteins, NPM1 and NCL localized in the nucleus and interacted with SIRT6 and SIRT7. NPM1 was identified as a novel substrate and its acetylation level decreased by both SIRT6 and SIRT7. Additionally, in senescent cells, the acetylation level of NPM1 was increased in conjunction with decreased level of SIRT6 and SIRT7, suggesting that acetylation of NPM1 is regulated by SIRT6 and SIRT7 in the aging process. Our findings provide insights on functional relationship between SIRT6 and SIRT7 as well as their roles in DNA repair, chromatin assembly and cancer cell proliferation, and aging.
Citation Format: Namgyu Lee, Jung-Hee Kwon, Sung Jin Park, Kwan Yong Choi. Comparative studies on SIRT6 and SIRT7 interactomes: Implications of important roles in cancer via associating with interacting partners. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 351. doi:10.1158/1538-7445.AM2014-351
Abstract 3511: Sustained adrenergic signaling promotes cervical cancer progression
Authors: Sadaoui Nouara C. , Armaiz-Pena Guillermo N. , Nagaraja Archana S. , Rupaimoole Rajesha , Previs Rebecca A. , Dalton Heather J. , Lingegowda Mangala S. , Ramondetta Lois M. , Sood Anil K. , Lutgendorf Susan K. , Cole Steve W. 
Published: May 2015

Abstract
Objective: Chronic stress and sustained adrenergic signaling promote tumor progression. The underlying mechanisms behind this process are not well understood. We examined the effects of sustained adrenergic signaling on cervical cancer progression through increased expression of HPV oncogenes, E6 and E7.
Methods: Beta-adrenergic receptor (ADRB) positive cervical cancer cell lines (CaSki and SiHa) were treated with norepinephrine (NE) or isoproterenol (ISO) to analyze intracellular responses. Migration, invasion and anoikis assays were performed to elucidate the resultant biological effect of NE and ISO. ADRB expression levels were examined from cervical cancer patient tumor samples.
Results: ADRB expression was determined for cervical cell lines (CaSki, SiHa, and C33A) using qRT-PCR. CaSki and SiHa cells express ADRB1, ADRB2, and ABRB3. Cells exposed to NE for 30 min showed elevated cyclic AMP activity. After treatment with NE or ISO, mRNA levels from HPV oncogenes, E6 and E7, were significantly elevated in the SiHa and CaSki cells. NE exposure resulted in a significant increase in invasion and migration of cervical cancer cells, while E6 siRNA abrogated these effects. After 48 hours of NE or ISO exposure, CaSki cells showed a 30% reduction in anoikis. Among 166 tumor samples evaluated from cervical cancer patients, 85% had increased ADRB1 expression and 61% had increased ADRB2 expression. Tumor stage or grade was not related to ADRB expression. ADRB1 expression was not correlated with patient survival outcomes (p = 0.86); however, patients with high ADRB2 expressed had decreased overall survival (p=0.038).
Conclusion: Increased adrenergic signaling promotes cervical cancer progression. Disruption of this pathway could provide a novel complement to current therapies.
Citation Format: Nouara C. Sadaoui, Guillermo N. Armaiz-Pena, Archana S. Nagaraja, Rajesha Rupaimoole, Rebecca A. Previs, Heather J. Dalton, Mangala S. Lingegowda, Lois M. Ramondetta, Anil K. Sood, Susan K. Lutgendorf, Steve W. Cole. Sustained adrenergic signaling promotes cervical cancer progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3511. doi:10.1158/1538-7445.AM2014-3511
Abstract 3520: TAZ (WWTR1), a key transcription co-activator of hippo-pathway, promotes hepatocellular carcinoma progression via PI3K/Akt/mTOR pathway
Authors: Hayashi Hiromitsu , Kuroki Hideyuki , Nakagawa Shigeki , Higashi Takaaki , Sakamoto Keita , Yokoyama Naomi , Ishiko Takatoshi , Beppu Toru , Baba Hideo 
Published: May 2015

Abstract
Introduction: The contact inhibition of proliferation is crucial for well-controlled organogenesis. Its disruption results in sustained cell proliferation, which is a hallmark of solid tumors. The Hippo signaling pathway has been implicated in contact inhibition of proliferation. Here, we investigated the role of TAZ (WWTR1), a key transcription co-activator of hippo-pathway, in HCC progression. Methods and Results: In HCC patients, the high TAZmRNA expression examined by real time PCR showed worsen survival outcomes compared with low expression group. Additionally, the tumor size in High TAZmRNA expression group was significantly larger than that in low expression group, and its high protein expression in HCC was deeply associated with the cell proliferative activity. A knockdown of TAZ expression in HCC cell lines attenuated the cell growth accompanying the downstream gene expressions (CTGF and CYR61). As the TAZ-mediated signaling pathway in cell growth, a knockdown of TAZ expression using RNAi inactivated the PI3K/Akt/mTOR pathway. Conclusion: Thus, TAZ plays a crucial role in tumor progression by accelerating cell growth via a PI3K/Akt/mTOR pathway, and tumoral TAZmRNA expression level may be a useful prognostic biomarker in HCC.
Citation Format: Hiromitsu Hayashi, Hideyuki Kuroki, Shigeki Nakagawa, Takaaki Higashi, Keita Sakamoto, Naomi Yokoyama, Takatoshi Ishiko, Toru Beppu, Hideo Baba. TAZ (WWTR1), a key transcription co-activator of hippo-pathway, promotes hepatocellular carcinoma progression via PI3K/Akt/mTOR pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3520. doi:10.1158/1538-7445.AM2014-3520
Abstract 3527: YYEI motif is critical to oncogenicity of 14-3-3 proteins
Authors: Chang Wen-Hsin , Chen Ching-Hsien , Hong Qi-Sheng , Chen Jian-Wei , Yu Sung-Liang , Chen Chiung-Tong 
Published: May 2015

Abstract
14-3-3 family consists of seven highly conserved isoforms and most of them are identified as oncogenes in various types of cancer except for 14-3-3σ, a well-known tumor suppressor. To clarify the suppressor characteristic of 14-3-3σ divergent from others, we found that the major difference between the other oncogenic members and 14-3-3σ by protein alignment was an amino acid substitution (Y180H) by which the SH2-binding motif (YYEI) is disrupted and cannot be phosphorylation. Thus, we generated a H180Y 14-3-3σ mutant and investigated the impact of the acquired YYEI motif on the tumor suppression. First, we found that 14-3-3σ decreased cancer invasion. Surprisingly, the H180Y mutant not only enhanced cell invasion but increased cell viability. Meanwhile, the interaction between H180Y mutant and Src was higher than wild type. It indicates one amino acid substitution switches 14-3-3σ from tumor suppressor to oncogene. Hence, the YYEI motif might be important for the oncogenicity of other 14-3-3 proteins. Indeed, we demonstrated that 14-3-3ζ interacted with Src through Y178 phosphorylation, which is crucial for the binding of 14-3-3ζ with Src-SH2 domain. Owing to the importance of Y178 phosphorylation in the 14-3-3ζ/Src interaction, we introduced the Y178F 14-3-3ζ mutant to lung cancer cells and confirmed that Y178 phosphorylation is important for the increase of invasion and viability. Furthermore, we also revealed an amino acid switch of 14-3-3σ from YYEI to HYEI during evolutionary progression. Taken together, our findings suggest that YYEI motif is essential for 14-3-3 proteins to interact with Src and to regulate Src-mediated cell functions.
Citation Format: Wen-Hsin Chang, Ching-Hsien Chen, Qi-Sheng Hong, Jian-Wei Chen, Sung-Liang Yu, Chiung-Tong Chen. YYEI motif is critical to oncogenicity of 14-3-3 proteins. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3527. doi:10.1158/1538-7445.AM2014-3527
Abstract 3533: ADAM9 regulates microRNAs expression for lung cancer metastasis
Authors: Sher Yuh-Pyng , Wang Li-Ju , Tsai Mong-Hsun , Kuo Ting-Ting , Chuang Eric Y. , Lai Liang-Chuan 
Published: May 2015

Abstract
Lung cancer is the leading cause of cancer death worldwide, and brain metastasis is a major cause of morbidity and mortality in lung cancer. Currently, it is not clear which molecules or what mechanisms mediate lung cancer brain metastasis. To explore this question, we compared our established brain-metastatic lung cancer sublines with their parental cancer cells, and identified ADAM9 (a disintegrin and metalloprotease 9) was overexpressed in metastatic sublines. Knocking down ADAM9 expression in lung cancer cells also showed significant reduction of lung cancer brain metastasis in vitro and in vivo. Furthermore, using a genome-wide approach to screen ADAM9-related mRNAs and microRNAs involved in brain metastasis, we identified that CDH2, encoding N-cadherin, was up-regulated by ADAM9 in brain-metastatic lung cancer sublines, and the 3′UTR of CDH2 contains the predicted binding sites of several microRNAs that were down-regulated in ADAM9-overexpressed cancer cells. Luciferase assays and western blot analysis showed that CDH2 is a target gene of microRNAs. The up-regulation of microRNAs, in turn, reduced the expression of its target gene and further inhibited the migration ability of aggressive lung adenocarcinoma cells. This study revealed that ADAM9 activates CDH2 through the release of microRNA inhibition of CDH2 in lung adenocarcinoma and plays a role in lung cancer metastasis.
Citation Format: Yuh-Pyng Sher, Li-Ju Wang, Mong-Hsun Tsai, Ting-Ting Kuo, Eric Y. Chuang, Liang-Chuan Lai. ADAM9 regulates microRNAs expression for lung cancer metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3533. doi:10.1158/1538-7445.AM2014-3533
Abstract 3542: Upregulation of microRNA-372 & 373 associates with cervical lymph node metastasis and poor prognosis of oral carcinomas
Authors: Liu Chung J. , Tu Hsi-Feng , Cheng Hui-Wen , Chang Kuo-Wei 
Published: May 2015

Abstract
Purpose: Oral squamous cell carcinoma (OSCC) is prevalent worldwide, and survival in OSCC has not improved significantly in the last few decades. MicroRNAs (miRNAs) have an important regulatory role in human cancer including oral carcinogenesis. MicroRNA 372 and microRNA 373 play as oncogenic and tumour-suppressive functions of between different human maligngncy. This study investigated the microRNA-372 and microRNA 373 expression and their clinical implication in OSCC.
Experimental Design: Fifty patients with primary OSCC were included in the study. Primary cancer cells and matched normal oral epithelium were purified by laser capture microdissection. RNA were extracted from these samples. The expression levels of miR-372 and miR-373 in the tissue of OSCC patients were measured by quantitative RT-PCR.
Results: both miR-372 and miR-373 was up-regulated in OSCC tissue relative to control mucosa. Among different clinical variables, over-expression of miR-372 and miR-373 were associated with nodal metastasis, lymphovascular invasion and poor survival. Multivariate analysis showed that both high miR-372 and miR-373 expression were independent predictors for poor survival in OSCC.
Conclusion: Over expression of miR-372 and miR-373indicate worse survival in OSCC.
Citation Format: Chung Ji Liu, Hsi-Feng Tu, Hui-Wen Cheng, Kuo-Wei Chang. Upregulation of microRNA-372 & 373 associates with cervical lymph node metastasis and poor prognosis of oral carcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3542. doi:10.1158/1538-7445.AM2014-3542
Abstract 3543: A long noncoding RNA plays a critical role in Bcr-Abl-mediated cellular transformation
Authors: Guo Guijie , Kang Qingzheng , Chen Qinghuang , Jing Ouyang , Chen Jilong 
Published: May 2015

Abstract
It is well documented that malignant transformation of myeloid and lymphoid cells by Bcr-Abl involves the dysregulation or mutation of a variety of protein-coding genes that are normally involved in regulating the proliferation and survival of hematopoietic cells. However, the functional relevance of long noncoding RNAs (lncRNAs) and their in vivo regulation during Bcr-Abl-mediated tumorigenesis remain unknown, although recent studies have shown that aberrant expression of lncRNAs is associated with various human cancers. In this study, we performed a comprehensive analysis of lncRNAs in human CML cells using an lncRNA cDNA microarray, and identified an lncRNA termed lncRNA-BGL3 that acted as a key regulator of Bcr-Abl-mediated cellular transformation. Notably, we observed that lncRNA-BGL3 was highly induced in response to disruption of Bcr-Abl expression or by inhibiting Bcr-Abl kinase activity in K562 cells and leukemic cells derived from CML patients. Ectopic expression of lncRNA-BGL3 sensitized leukemic cells to undergo apoptosis and inhibited Bcr-Abl-induced tumorigenesis. Furthermore, transgenic mice expressing lncRNA-BGL3 were generated. We found that transgenic expression of lncRNA-BGL3 alone in mice was sufficient to impair primary bone marrow transformation by Bcr-Abl. Interestingly, we identified that lncRNA-BGL3 was a target of miR-17, miR-93, miR-20a, miR-20b, miR-106a and miR-106b, microRNAs that repress mRNA of PTEN. Further experiments demonstrated that lncRNA-BGL3 functioned as a competitive endogenous RNA (ceRNA) for binding these microRNAs to cross-regulate PTEN expression. Additionally, our experiments have begun to address the mechanism of how lncRNA-BGL3 is regulated in the leukemic cells and showed that Bcr-Abl repressed lncRNA-BGL3 expression through c-Myc-dependent DNA methylation. Taken together, these results reveal that Bcr-Abl-mediated cellular transformation critically requires silence of tumor suppressor lncRNA-BGL3 and suggest a potential strategy for the treatment of Bcr-Abl-positive leukemia.
Citation Format: Guijie Guo, Qingzheng Kang, Qinghuang Chen, Ouyang Jing, Jilong Chen. A long noncoding RNA plays a critical role in Bcr-Abl-mediated cellular transformation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3543. doi:10.1158/1538-7445.AM2014-3543
Abstract 3544: Tumor suppressor function of loc285194 in breast cancer
Authors: CHI YAYUN , Huang Sheng , Wu Jiong 
Published: May 2015

Abstract
Accumulating studies have focused on the oncogenic and tumor suppressive roles of the newly identified lncRNAs. LOC285194 was found to be associated with poor survival of osteosarcoma patients and colorectal cancer patients. Also loc285194 is reported to be a direct transcription target of p53 and could suppress cell growth. However, its role in breast cancer (BC) remains unknown. The aim of this study was to examine the expression pattern of loc285194 in BC and to evaluate its biological role and clinical significance in prediction of prognosis. In this study, we examined expression of loc285194 in 20 pairs of BC cancer tissues and adjacent noncancerous tissues (ANCT), also in 151 BC tissues, 14 BC cell lines and one normal breast cell line. It showed that loc285194 expression was lower both in BC samples and in BC cell lines compared with corresponding normal control. Loc285194 expression was correlated with menopausal status. Postmenopausal patients had a lower loc285194 expression level comparing with premenopausal patients (p=0.040). Moreover, low loc285194 expression was correlated with a relatively poor survival status (p=0.023) and a poor tumor differentiation (p=0.035). The Kaplan-Meier survival curves indicated that the overall survival (OS) was significantly poor in BC patients who showed low loc285194 expression. Furthermore, expression of loc285194 is significantly associated with worse prognosis independent of prognostic markers in estrogen receptor (ER) negative tumor samples (p = 0.05). Our studies indicate that loc285194 may represent a new marker of prognosis and it is a potential therapeutic target for breast cancer especially for ER negative breast cancer.
Citation Format: YAYUN CHI, Sheng Huang, Jiong Wu. Tumor suppressor function of loc285194 in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3544. doi:10.1158/1538-7445.AM2014-3544
Abstract 3559: Long non-coding RNA subtype classification of clear-cell renal cell carcinoma
Authors: Malouf Gabriel G. , Zhang Jianping , Tannir Nizar , Thompson Erika J. , Khayat David , Spano Jean-Philippe , Su Xiaoping 
Published: May 2015

Abstract
Background: Long non-coding RNAs (lncRNA) play a key role in regulating cell physiology through different mechanisms including regulation of transcription and splicing, and recruitment of histone-modifying enzymes. The portrait of lncRNA in kidney cancers remains fully unknown.
Material and Methods: we performed a genomic analysis of GENCODE lncRNAs in clear-cell renal cell carcinoma (ccRCC), using The Cancer Genome Atlas (TCGA) molecular RNAseq profiles of 475 primary tumors. Furthermore, we described global correlations between lncRNA and expression of cis- and trans-acting genes, and established lncRNA expression subtypes based on distinct signatures. In addition, lncRNA expression was correlated with miRNA, copy-number alterations and the chromatin landscape of human kidney.
Results: Using stringent criteria (RPKM ≥1 in at least 10% of ccRCC), we identified 1,934 lncRNAs and predicted those that are potential drivers of cancer progression through integrative analysis. The expression of 1,057 (54.6%) lncRNAs showed a positive correlation with the mRNA expression of their neighboring genes, while only 13 (0.7%) lncRNAs showed a negative correlation. Overall, 844 (43.6%) lncRNAs were pre-marked by H3K4me3 in normal kidney, suggesting that those lncRNA might arise from promoter-associated elements. Conversely, only 81 (4.2%) and 182 (9.4%) lncRNAs were pre-marked by H3K36me3 and H3K27me3, respectively. Unsupervised clustering of lncRNA expression revealed four robust subtypes, which differ from the ccRCC transcriptomic subgroups. Interestingly, patients belonging to cluster II (n=111) displayed poor overall survival as compared to patients of other clusters (p=2.6x10-6). Intriguingly, there were 37 (7.8%) ccRCC belonging to cluster IV, and those were enriched for TFE3/TFEB RCC. Furthermore, tumors within cluster IV were devoid from 3p loss and 5q gain which represent the most frequent genomic aberrations in ccRCC. Finally, GREAT analysis reveals that overexpressed lncRNA in cluster IV were exclusively enriched for genes belonging to collecting duct (p=1.6x10-13) highly suggesting that their cell of origin might be different.
Conclusion: This study describes the first portrait of lncRNA in ccRCC and proposes a robust lncRNA subtype classification of ccRCC, which may serve in predicting patient outcome. Furthermore, we identified a small ccRCC subgroup with distinct lncRNA and karyotypic phenotype.
Citation Format: Gabriel G. Malouf, Jianping Zhang, Nizar Tannir, Erika J. Thompson, David Khayat, Jean-Philippe Spano, Xiaoping Su. Long non-coding RNA subtype classification of clear-cell renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3559. doi:10.1158/1538-7445.AM2014-3559