bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1149: Interaction with NHERF1 enhances protein stability of G protein-coupled estrogen receptor
Authors: Meng Ran , Xiong Ying , Zhao Yuan , Wang Yan , Tao Tao , Wang Qiqi , Liu Hua , Wang Songlin , Qin Qiong , Zheng Junfang , He Junqi 
Published: July 2016

Abstract
G Protein-Coupled Estrogen Receptor (GPER), also called GPR30, has been demonstrated to play important roles in a variety of physiological and pathological responses, especially in cancer cells proliferation, migration and invasion. Despite increasing evidences have showed clinical correlations between GPER expression level and poor prognosis in human cancer specimens, little is known regarding the regulation of GPER expression level, especially in protein level. Our previous studies have shown that PDZ protein NHERF1 can interact with ACTN4 (FASEB J. 2015) or PTEN (Endocrinology. 2011) and prevent their degradation. In this study, NHERF1 was demonstrated to interact with GPER in HEK293 cells and breast cancer cells MCF7 and T47D. GST Pull-down, Co-IP and immunocytochemistry analysis revealed that this interaction was mediated by the PDZ2 domain of NHERF1 and the carboxyl terminal of GPER. Mutation of the last c-terminal amino acid of GPER V375A could abolish the interaction of NHERF1 with GPER. Change of NHERF1 expression level by overexpression or knockdown affects the overall protein level of GPER. NHERF1 overexpression improved the GPER protein stability by inhibiting the receptor degradation via ubiquitin-proteasome pathway in an interaction dependent manner. Further analysis of public TCGA data revealed that NHERF1 expression level positively associated with activation of GPER downstream genes in invasive breast cancer, in which GPER mRNA level was similar with that of normal breast tissue. Our findings identify NHERF1 as a novel binding partner for GPER and uncover a novel role of NHERF1 in promoting GPER protein stability by inhibiting ubiquitin-proteasome degradation of the receptor. Considering the importance of GPER in breast cancer progression, these findings may help elucidate mechanisms associated with breast cancer invasion and metastasis.
Citation Format: Ran Meng, Ying Xiong, Yuan Zhao, Yan Wang, Tao Tao, Qiqi Wang, Hua Liu, Songlin Wang, Qiong Qin, Junfang Zheng, Junqi He. Interaction with NHERF1 enhances protein stability of G protein-coupled estrogen receptor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1149.
Abstract 1157: Single nucleotide polymorphisms in ARHGAP17 are associated with pancreatic intraepithelial neoplasia in 2401 autopsied elderly patients
Authors: Matsuda Yoko , Tanaka Masashi , Seki Atsuko , Nonaka Keisuke , Nishimura Makoto , Ishiwata Toshiyuki , Yoshimura Hisashi , Takubo Kaiyo , Arai Tomio 
Published: July 2016

Abstract
Background: Aging, obesity, smoking, alcohol consumption, diabetes, and pancreatitis have been reported to be the risk factors for pancreatic cancer. There is much evidence showing that single nucleotide polymorphisms (SNPs), especially those in BCAR1, PDX1, ZNRF3, or TERT, influence one's predisposition to pancreatic cancers and survival. However, the association between SNP and pancreatic precancerous lesions is not yet clarified. In the present study, we clarified the clinicopathological features of precancerous lesions of the pancreas by examining autopsied elderly cases. Methods: We analyzed serial autopsy cases (men, 1326; women, 1075; mean age, 80.6) of pancreatic intraepithelial neoplasia (PanIN) and performed a comparative analysis based on the sex, age, and body mass index (BMI) of the patients. The SNPs were analyzed using HumanExome BeadChip. Results: The occurrence of PanIN increased with advanced age. Approximately, 60% of the elderly patients showed low-grade PanIN. The autopsy cases showed that the occurrence of low-grade PanIN was positively correlated with the female sex, advanced age, and increase in BMI. The SNPs of the ARHGAP17 gene, p.G782D (rs28365822) and rs1106576, were risk factors for PanIN (Table, P&lt;0.0001, *adjusted with age and gender). Discussion: A high incidence of low-grade PanIN in the elderly might be related to the increased risk of pancreatic cancer in the elderly. Further studies are needed to clarify the role of SNPs of ARHGAP17 in the carcinogenesis of pancreatic cancer. Association between SNPs in ARHGAP17 and pancreatic intraepithelial neoplasiasGenotypePanIN (-)PanIN (+)P valueunadjustedadjusted*rs28365822(%)Chi squareDominant-FisherLogistic regressionOdds ratio(95% confidence interval)CC1028(99.1)1192(96.7)&lt;0.00010.000040.00023.934.05TC9(0.9)41(3.3)(1.90-8.12)(1.94-8.47)TT0(0)0(0)GenotypePanIN (-)PanIN (+)P valueunadjustedadjusted*rs1106576(%)Chi squareDominant-FisherLogistic regressionOdds ratio(95% confidence interval)TT1027(99.1)1192(96.7)&lt;0.00010.000040.00023.934.05TC9(0.9)41(3.3)(1.90-8.12)(1.94-8.47)CC0(0)0(0)
Citation Format: Yoko Matsuda, Masashi Tanaka, Atsuko Seki, Keisuke Nonaka, Makoto Nishimura, Toshiyuki Ishiwata, Hisashi Yoshimura, Kaiyo Takubo, Tomio Arai. Single nucleotide polymorphisms in ARHGAP17 are associated with pancreatic intraepithelial neoplasia in 2401 autopsied elderly patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1157.
Abstract 1160: FRY Inhibits progression and metastasis of breast cancer through activating Hippo signaling pathway
Authors: Zhang Hao , Fei Fan , Chen Xushen , Ceng Zi , Tang Xiaojiang , Zarbl Helmut , Ren Xuefeng 
Published: July 2016

Abstract
Background: Recently, we reported that using quantitative trait locus (QTL) mapping in differentially susceptible rat strains, we identified Fry, the mammalian ortholog of the furry gene in Drosophila melanoganster, as a candidate mammary carcinoma susceptibility gene (Mcs30). Preliminary studies of rat Fry gene suggest that Fry may play a key role in epithelial-mesenchymal transition (EMT), tumor progression and metastasis.
Methods: In the present study, we modified and established multiple breast cancer cell lines with enhanced expression of either wildtype or mutated human FRY gene. We examined the anti-tumorigenic and anti-metastatic effects of enhanced FRY expression on these cell lines in vitro and in vivo. We also utilized RNA-seq and proteomic approach to dissect FRY-regulated signaling molecules and pathways.
Results: Ectopic expression of wild-type FRY significantly diminished tumorigenicity and metastasis of breast cancer cells both in vitro and in animal studies, particularly in the triple negative breast cancer cell line, MDA-MB-231 cells. Relative to the rapidly tumors growth of MDA-MB-231 cells in vitro and in nude mice assay, the growth of MDA-MB-231 cells ectopically expressing the FRY significantly reduced. In comparison, the anti-tumorigenic effects of mutated FRY were compromised but remained significant. Further, we showed that FRY's effects in suppressing proliferation, invasion, and metastasis of breast cancer cells were partially through the activation of Hippo signaling pathway.
Conclusions: These results provide direct evidence in supporting the important role of FRY in breast cancer progression and metastasis, and first time reveal a connection between FRY and the Hippo signaling pathway.
Citation Format: Hao Zhang, Fan Fei, Xushen Chen, Zi Ceng, Xiaojiang Tang, Helmut Zarbl, Xuefeng Ren. FRY Inhibits progression and metastasis of breast cancer through activating Hippo signaling pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1160.
Abstract 1162: Multiple genes on chromosome 17q25 were involved in sporadic esophageal squamous cell carcinoma development
Authors: Iwaya Takeshi , Amano Suburu , Endo Fumitaka , Akiyama Yuji , Shioi Yoshihiro , Kume Kohei , Nishizuka Satoshi , Ito Chie , Sasaki Akira , Mimori Koshi 
Published: July 2016

Abstract
[Background] Tylosis is an autosomal dominant skin disorder that is associated with the early onset of esophageal squamous cell carcinoma (ESCC) in several families. The tylosis esophageal cancer (TOC) gene locus has been mapped to chromosome 17q25.1 using linkage analyses. This region is also frequently lost in sporadic ESCC. [Materials and Methods] Gene expression profiles on 17q25 in tumor samples from 3 ESCC patients were analyzed using RNA-seq. We validated the expression status of candidate genes in samples from 90 ESCC patients using qRT-PCR. Direct sequence, microsatellite LOH analysis, and methylation assay were also performed in the candidate gene, ST6GALNAC1. Mutation profiles of genes on 17q were also evaluated by exome sequence analysis from 144 ESCC patients. [Result] EVPL and ST6GALNAC1 were found to be significantly downregulated in tumor samples using RNA-seq. Significant downregulation of ST6GALNAC1 and EVPL expression in cancer tissues was confirmed by qRT-PCR in 90 ESCC samples. Although direct sequence of ST6GALNAC1 demonstrated missense mutations in 7 out of 46 (15%) cases, these mutations were not tumor specific. ST6GALNAC1 expression was significantly upregulated in 5-aza-dC treatment groups compared with control in the 5 ESCC cell lines. LOH in ST6GALNAC1 gene locus were identified 18 of 27 informative cases (67%). On chromosome 17q, exome sequence revealed that recurrent mutations were observed only in ZNF750 (14.5%) on 7q25.3. Recently, missense mutations in RHBDF2 were identified tylosis familys. However, RHBDF2 mutation was not observed in sporadic ESC samples by exome sequence analysis. [Conclusion] Our results suggest that ST6GALNAC1 is a putative tumor suppressor gene for ESCC. Furthermore, recent studies on tylosis families and our results on sporadic ESC suggest that multiple genes on chromosome 17q25 are involved in ESCC development.
Citation Format: Takeshi Iwaya, Suburu Amano, Fumitaka Endo, Yuji Akiyama, Yoshihiro Shioi, Kohei Kume, Satoshi Nishizuka, Chie Ito, Akira Sasaki, Koshi Mimori. Multiple genes on chromosome 17q25 were involved in sporadic esophageal squamous cell carcinoma development. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1162.
Abstract 1164: Semaphorin 3C promotes de novo steroidogenesis in androgen-deprived prostate cancer cells
Authors: Yenki Parvin , Adomat Hans , Cheng Chi Wing , Ong Christopher 
Published: July 2016

Abstract
Introduction: This project aims to study the biological role of Semaphorin 3C (SEMA3C) in castration resistant prostate cancer (CRPC) progression. We have found that SEMA3C is a key driver of prostate cancer (PCa) growth through activation of epidermal growth factor receptor (EGFR) and cMet receptor tyrosine kinase (RTK) pathways. RTK signalling activation has been shown to induce de novo steroidogenesis, therefore we hypothesize that SEMA3C-mediated RTK signalling may contribute to CRPC progression through promotion of androgen biosynthesis in androgen-deprived PCa cells.
Methods: LNCaP and 22Rv1 cells stably overexpressing SEMA3C were compared to mock transfected cells with respect to their in vitro steroidogenesis, secreted hormone levels were measured by Liquid chromatography-mass spectrometry (LC-MS) technique. Also the expression of steroidogenic enzymes and regulatory proteins were tested by quantitative PCR and western blotting. De novo steroidogenesis was detected by pulsing cells with C14-labeled acetate as a steroid precursor; production of intermediates was measured by scintillation.
Results: Steroid analysis showed that SEMA3C overexpression can significantly elevate testosterone and dihydrotestosterone secretion by prostate cancer cells. SEMA3C is also able to upregulate STAR, CYP17A1, HSD17β3, AKR1C3 and SRD5A1 expression. Steroid analysis of SEMA3C-overexpressing LNCaP cells incubated with C14-labeled acetate resulted in the increase of the radioisotope-labeled testosterone and pregnenolone.
Conclusions: These findings indicate that SEMA3C can promote steroid biosynthesis in androgen deprived prostate cancer cells, thereby SEMA3C signaling pathway can contribute to maintain active AR signaling in CRPC cells. This research line will be followed to measure intratumoral androgen level by inducing subcutaneously xenografted tumors in athymic nude mice. Tumor homogenates’ steroids will then be extracted and run on LC-MS system.
Citation Format: Parvin Yenki, Hans Adomat, Chi Wing Cheng, Christopher Ong. Semaphorin 3C promotes de novo steroidogenesis in androgen-deprived prostate cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1164.
Abstract 1177: The role of nischarin in the breast tumor microenvironment
Authors: Maziveyi Mazvita , Dong Shengli , Alahari Suresh K. 
Published: July 2016

Abstract
Women with denser breasts, have a higher risk of developing breast cancer. Breast density reflects the amount of connective tissue and collagen present. During metastasis, tumor cells move through tracks of extracellular matrix (ECM). A stiff and ordered tissue microenvironment is necessary for tumor cell invasiveness. Matrix stiffness is mediated by ECM fiber organization and cell-matrix adhesions. Our lab is investigating a tumor suppressor that contributes to ECM organization. The protein Nischarin interacts with a number of signaling proteins such as integrin α5, PAK1, LIMK1, LKB1, MLCK, ERK and Rac1 to prevent cancer cell migration. Our data shows that spontaneous breast tumors from wild-type (WT) animals have reduced ECM fiber expression and organization compared to those from homozygous Nischarin Null mice. Furthermore, we have found Nischarin to alter integrin and focal adhesion signaling, therefore affecting cell-matrix adhesions. We hypothesize that the absence of Nischarin in the breast tumor leads to increased matrix stiffness, through increased fiber organization, and altered cell-matrix adhesions. Since no breast tumor suppressors have been linked to collagen and fibronectin ECM remodeling, we present a novel role for Nischarin in organizing the ECM. By integrating cell signaling with optical and computational instrumentation, we will assess the role of Nischarin in the bidirectional cellular/matrix crosstalk, which will add to our understanding of the metastatic process in breast cancer.
Citation Format: Mazvita Maziveyi, Shengli Dong, Suresh K. Alahari. The role of nischarin in the breast tumor microenvironment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1177.
Abstract 1178: Runx1 is obligatory for mammary epithelial cell morphology and phenotype
Authors: Hong Deli , Messier Terri , Fritz Andrew , Browne Gillian , Stein Janet , Lian Jane , Stein Gary 
Published: July 2016

Abstract
Introduction: Runx1 belongs to the Runx family of transcription factors. Translocation of Runx1 is well established as a causative factor of leukemia. However the recognition of Runx1 expression in epithelial lining cells of glands suggests that Runx1 functions in maintaining the integrity of that cell layer. Recent studies have identified Runx1 as one of the top genes mutated in breast cancers. Further Runx1 levels are decreased in high-grade primary breast tumors compared to low/mid-grade tumors. Based on these findings, we raise the hypothesis that Runx1 is a tumor suppressor that functions to maintain the normal epithelial phenotype and that loss of Runx1 could promote epithelial to mesenchymal (EMT). Methods and results: We used two human breast cancer cell models systems, the MCF10A to MCF7/T47D and to MDA-MB-231 and the MCF10A progression model from normal-like mammary epithelial cells (MCF10A) to tumorigenic (MCF10AT1) and to metastatic (MCF10CA1a) cells. We observed that the level of Runx1 is decreased in tumorigenic cells. To understand Runx1 function, Runx1 was depleted by shRNA in mammary epithelial cells that resulting in disrupted/altered cellular morphology and suppressed expression of the epithelial gene E-cadherin. To reinforce this observation, EMT was induced by addition of TGFB1 or by growth factor depletion in MCF10A cells. A striking Runx1 decrease resulted suggesting that Runx1 has a crucial role in preventing EMT. Furthermore our analysis of breast tumors and survival data supports the above finding that loss of Runx1 promotes tumor progression.
Conclusion and Impact: Our results highlight an essential role for Runx1 in maintaining normal epithelial phenotype and preventing epithelial to mesenchymal transition as well as tumor progression in breast cancer. Identifying this Runx1 mechanism provides the basis for a novel strategy to treat early stage breast cancer.
Citation Format: Deli Hong, Terri Messier, Andrew Fritz, Gillian Browne, Janet Stein, Jane Lian, Gary Stein. Runx1 is obligatory for mammary epithelial cell morphology and phenotype. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1178.
Abstract 1180: The TCA cycle transferase DLST is critical for MYC-mediated leukemogenesis
Authors: Anderson Nicole , Li Dun , Peng H.L. , Mansour Marc , Laroche Fabrice , Gjini Evisa , Helman Daniel , Harrold Itrat , Meng Le , Sanda Takaomi , Amsterdam Adam , Neuberg Donna , Denton Travis , Singh Anurag , Look A Thomas , Feng Hui 
Published: July 2016

Abstract
The proto-oncogene MYC has been implicated in the pathogenesis of many human cancers, including hematological and solid malignancies1. In the majority of T-ALL cases, MYC is aberrantly expressed downstream of activated NOTCH1 mutations. Despite the pivotal role of MYC in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and many other cancers, the mechanisms underlying MYC-mediated tumorigenesis remain inadequately understood2. Here we utilized a well-characterized zebrafish model of Myc-induced T-ALL for genetic studies to identify novel genes contributing to disease onset. We found that heterozygous inactivation of a tricarboxylic acid (TCA) cycle enzyme, dihydrolipoamide S-succinyltransferase (Dlst), significantly delayed tumor onset. Concordant with our zebrafish results, RNAi knockdown of DLST led to decreased cell viability and induction of apoptosis in human T-ALL cell lines. DLST is the E2 transferase of the -ketoglutarate dehydrogenase complex (KGDHC), which converts -ketoglutarate (-KG) to succinyl-CoA in the TCA cycle3. Polar metabolomics profiling revealed that the TCA cycle was disrupted by DLST knockdown in human T-ALL cells, as demonstrated by an accumulation of -KG and its precursor glutamine, as well as a loss of succinyl-CoA. Addition of succinate, the downstream TCA cycle intermediate, to human T-ALL cells was sufficient to rescue defects in cell viability caused by DLST inactivation. Taken together, our studies identify DLST as an important mediator of MYC-driven leukemogenesis and provide compelling evidence for the metabolic dependence of T-ALL cells on the TCA cycle.
1. Nesbit CE, Tersak JM, Prochownik EV. MYC oncogenes and human neoplastic disease. Oncogene 1999 May 13; 18(19): 3004-3016.
2. Sharma VM, Calvo JA, Draheim KM, Cunningham LA, Hermance N, Beverly L, et al. Notch1 contributes to mouse T-cell leukemia by directly inducing the expression of c-myc. Molecular and cellular biology 2006 Nov; 26(21): 8022-8031.
3. Sheu KF, Blass JP. The alpha-ketoglutarate dehydrogenase complex. Ann N Y Acad Sci 1999; 893: 61-78.
Citation Format: Nicole Anderson, Dun Li, H.L. Peng, Marc Mansour, Fabrice Laroche, Evisa Gjini, Daniel Helman, Itrat Harrold, Le Meng, Takaomi Sanda, Adam Amsterdam, Donna Neuberg, Travis Denton, Anurag Singh, A Thomas Look, Hui Feng. The TCA cycle transferase DLST is critical for MYC-mediated leukemogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1180.
Abstract 1191: Anti-tumor effect of selective progesterone receptor modulator (ulipristal acetate) on endometrial cancer cell lines
Authors: Lee Ha-Young , Ko A Ra , Kang Dong-Woo , Kim Yu-Seon , Kim Su-Min , Kang Tae-Wook , Lee Shin-Wha , Kim Yong-Man 
Published: July 2016

Abstract
Background: Endometrial cancer is the most common malignancy of the female reproductive tract and the third most common cause of death from women's cancer. Risk factors of endometrial cancer include high levels of estrogen, obesity, diabetes mellitus, breast cancer, long term use of tamoxifen, late menopause, high blood pressure, and increasing age. Although the exact mechanisms in endometrial carcinogenesis due to chronic exposure are unclear, it is though that the pro-proliferative and DNA-damaging effects of estrogen and its metabolites, related with and insufficient counterbalance by progesterone, promote the hyper-proliferation and transformation of cells. Selective progesterone receptor modulator (SPRM) is an agent that acts on the progesterone receptor. Ulipristal acetate (UA) is one of SPRM and other SPRM, such as Mifepristone, showed inhibitory effect on various endometrial cancer cell lines. UA has been available as an emergency contraception and a treatment for uterine leiomyoma. The effect of UA on leiomyoma is decreasing neovascularization, proliferation, and viability.
Objective: This study was undertaken to investigate antitumor effect of UA and to explore the effect of combination treatment with chemotherapy drug in endometrial cancer.
Method: Inhibitory concentration (IC), proliferation assay, and migration assay were performed using Ishikawa, HEC-1-A, HEC-1-B, and/or patient-derived primary cancer cells (PCC). Different concentration of UA were treated in endometrial cancer cell lines and PCCs for the each assay. The CellTiter-Glo assay were performed to investigate IC50 in cell lines and PCCs. Crystal violet staining and wound healing assay were performed to examine cell proliferation and migration.
Results: UA inhibited cell viability of endometrial cancer cell lines and PCCs at high concentration, most abviously 10uM in dose-dependent manner. In combination treatment assay with paclitaxel, UA showed synergistic anti-tumor effect with low-dose of paclitaxel on cell lines and PCCs.
Conclusions: We showed that combination treatment of UA and paclitaxel effectively than single treatment by low dosage. In summary, we are actively exploring new effective applicable drugs for endometrial cancer, and our data suggest that UA may have therapeutic value with chemo-combination treatment of patients with endometrial cancer.
Citation Format: Ha-Young Lee, A Ra Ko, Dong-Woo Kang, Yu-Seon Kim, Su-Min Kim, Tae-Wook Kang, Shin-Wha Lee, Yong-Man Kim. Anti-tumor effect of selective progesterone receptor modulator (ulipristal acetate) on endometrial cancer cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1191.