bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4057: Modulation of actin binding proteins by docosahexaenoic acid reduces cancer cell migration
Authors: Ali Mehboob , Long Alexander , Heyob Kathryn M. , Srinivasan Asha , Rogers Lynette K. 
Published: May 2015

Abstract
Cancer is the leading cause of death worldwide and all age groups, including children, are at risk for cancer associated death. Disease progression and metastasis are major contributors to cancer-associated morbidity and mortality. Increased cell migration rate is characteristic of tumor progression and metastasis. Actin binding proteins regulate cytoskeletal remodeling at the leading edges of cancer cells, facilitate invasive organelle (invadopodia) formation, and promote higher migration rates. Docosahexaenoic acid (DHA), a poly unsaturated fatty acid, has been shown to inhibit the cancer cell metastatic phenotype. Here, we test the hypothesis that changes in actin binding proteins regulate cancer cell migration and that supplementing cells with DHA will prevent these changes. Non-cancer (MLE12) and cancer (A549, HCT116 and MCF7) cells were treated with 8-Br-cAMP and/or DHA. F-actin content was measured using confocal microscopy. Cell migration was estimated by wound assay and transwell apparatus. Actin binding proteins, profilin, cofilin, vimentin and gelsolin, were identified and quantified using confocal microscopy and western blot to evaluate wound edges and actin co- munoprecipitate, respectively. F-actin content and cell migration were increased by cAMP in association with changes in profilin, cofilin, vimentin and gelsolin levels. DHA treatment suppressed the increase in actin content and cell migration in cancer cells but not in non-cancer cells in association with altered levels of actin binding proteins. We postulate that DHA specifically inhibits cancer cell migration via alterations in actin binding proteins indicating a therapeutic potential against cancer cell metastasis. The changes in actin binding proteins could serve as biomarkers for cancer progression and as innovative therapeutic targets.
Citation Format: Mehboob Ali, Alexander Long, Kathryn M. Heyob, Asha Srinivasan, Lynette K. Rogers. Modulation of actin binding proteins by docosahexaenoic acid reduces cancer cell migration. [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 4057. doi:10.1158/1538-7445.AM2014-4057
Abstract 406: A potential new mechanism for PTEN to maintain genome stability
Authors: Gong Lili , Lin Shiaw-Yih 
Published: May 2015

Abstract
Purpose: PTEN (phosphatase and tensin homolog) is among the most mutated or lost tumor suppressors. Recent studies revealed that nuclear PTEN represses tumorigenesis by stabilizing the centromere, a highly condensed heterochromatin domain featured with long array of DNA repeats (namely, satellite DNA), repressive histones, such as trimethylated Histone H3 at Lys9 residue (H3K9me3), and heterochromatin proteins. Our studies are aimed to explore the molecular mechanism that PTEN regulates this heterochromatin structure and thus maintaining genome stability.
Methods and Results: Co-immunoprecipitation (Co-IP) assay showed that PTEN and the heterochromatin proteins directly interact. Chromatin immunoprecipitation (ChIP) assay showed that PTEN is enriched in satellite locus. Depletion of PTEN leads to abnormal heterochromatin structure, indicated by reduced H3K9m3 foci (detected by immunofluorescent staining) and occupancy to satellite locus (ChIP assay), decreased heterochromatin protein levels (Westernblot analysis), and overexpression of satellite transcripts (quantitative RT-PCR). Through a knockdown-and-mutant rescue strategy, we found that the C-terminal of PTEN is essential for its repressive function on satellite transcription. Furthermore, overexpression of the C-terminal truncated PTEN into PTEN-null BT549 cells, as compared to wild-type PTEN overexpression, lost its function to suppress cell growth (MTT assay), cell cycle progression (flow cytometry analysis) and protection from DNA damage (MTT and colony formation assays).
Conclusions: Our finding showed that PTEN guards the genome stability through maintaining the normal structure of heterochromatin domain.
Citation Format: Lili Gong, Shiaw-Yih Lin. A potential new mechanism for PTEN to maintain genome stability. [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 406. doi:10.1158/1538-7445.AM2014-406
Abstract 4063: Potential targets of PTP4A3 involved in uveal melanoma migration
Authors: Liot Geraldine , Anezo Oceane , Laurent Cecile , Maacha Selma , Planque Nathalie , Saule Simon 
Published: May 2015

Abstract
Uveal melanoma (UM) is the most frequent eye cancer in the adulthood and it represents 4-5% of all melanomas. Although at diagnosis over 95% of patients have disease limited to the eye, about 50% will develop metastases after a median time of three years. From transcriptomic study, we identified PTP4A3/PRL3 level as an efficient predictor of patient's survival. Overexpression of PTP4A3 in UM OCM-1 increased both cell migration and invasiveness.
We then got interested in identifying downstream targets of PTP4A3 and more precisely proteins linked to cytoskeleton. We first highlighted collapsin Response Mediator Protein (CRMP2) by 2-D electrophoresis of phosphorus-enriched UM OCM1 stably-expressing PTP4A3 or an inactive catalytic mutant of PTP4A3 (C104S). CRMP2 was dephosphorylated in presence of PTP4A3. CRMP2 expression in UM is inversely correlated with that of PTP4A3, suggesting an antagonistic role of these proteins in tumor progression. Through the use of shRNA in OCM-1, the downregulation of CRMP2 led to an increase in cell migration of PTP4A3-expressing OCM1. In addition, we focused on ATIP3, a protein encoded by the gene MTUS1, which binds to microtubules. In breast cancer, MTUS1 expression was shown to be downregulated in highly proliferative breast carcinomas of poor clinical outcome. Similarly, our transcriptomic analysis showed that expressions of PTP4A3 and MTUS1 were anti-correlated, suggesting that the reduction of MTUS1 gene and ATIP3 expression in UM would be of bad prognosis. In our OCM1 cells, we demonstrated that ATIP3 overexpression blocks proliferation however effect of ATIP3 overexpression on cell migration still need to be elucidaded.In conclusion, CRMP2 and ATIP3 may play a role in the metastatic process of UM tumors expressing high levels of the phosphatase.
Citation Format: Geraldine Liot, Oceane Anezo, Cecile Laurent, Selma Maacha, Nathalie Planque, Simon Saule. Potential targets of PTP4A3 involved in uveal melanoma migration. [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 4063. doi:10.1158/1538-7445.AM2014-4063
Abstract 4069: Capn4 contributes to tumor growth and metastasis of hepatocellular carcinoma by activation of FAK-Src signaling pathways
Authors: Dai Zhi , Zhou Jian , Fan Jia 
Published: May 2015

Abstract
Calpain small subunit 1 (Capn4) has been identified as a major gene that promotes metastasis of hepatocellular carcinoma (HCC). However, the mechanism by which Capn4 promotes progression of HCC is not understood. In this study, we found that Capn4 expression was increased in highly metastatic HCC cell lines and in tumor tissue from HCC patients compared to healthy patient tissue. Overexpression of Capn4 in HCC cells enhanced tumor cell growth in vitro and increased invasiveness, tumorigenicity, and lung metastasis in vivo. Protein microarray analyses in HCC cells with altered Capn4 levels (through Capn4 silencing or overexpression) showed that expression of multiple proteins was regulated by Capn4 and that the activation of focal adhesion kinase (FAK) signaling pathways might play a key role in Capn4-enhanced tumor development. Immunoprecipitation and western blotting verified that Capn4 was physically associated with FAK and promoted hyperactivity of the FAK-Src signaling pathway via increased phosphorylation of specific tyrosine residues of FAK, Src, and p130Cas. Knockdown of Capn4 expression suppressed the malignant behavior of HCC cells and inhibited the FAK-Src signaling pathway. Furthermore, Capn4-mediated invasion and metastasis of HCC cells required up-regulation of matrix metalloproteinase-2 (MMP2) through activation of this signaling pathway. Our clinical data revealed that Capn4 expression correlated well with the levels of phospho-FAK, and overexpression of both Capn4 and phospho-FAK correlates with the poorest survival outcomes in HCC. These results suggest that Capn4 can contribute to HCC growth and metastasis via activation of the FAK-Src Signaling pathway and MMP2. Capn4 could be a therapeutic target for HCC.
Citation Format: Zhi Dai, Jian Zhou, Jia Fan. Capn4 contributes to tumor growth and metastasis of hepatocellular carcinoma by activation of FAK-Src signaling pathways. [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 4069. doi:10.1158/1538-7445.AM2014-4069
Abstract 4077: Impact of RET/PTC3 oncogene's inflammatory and transformative signaling on tumorigenicity of thyroid and non-thyroid tumorigenic cell lines
Authors: Kari Suresh C. , Eisenlohr Laurence C. 
Published: May 2015

Abstract
Rearranged in transformation/ papillary thyroid carcinoma 3 (RET/PTC3 or RP3), is a unique fusion oncogene, responsible for a benign version of PTC. RP3 has an active inflammatory component leading to the secretion of various pro-inflammatory cytokines, however the role of inflammation in development and progression of PTC has not been clearly defined. Facilitating investigation of this issue is our finding that the transforming and inflammatory signals of RP3 can be functionally separated allowing us to study each in isolation. We generated several RP3 mutants ablated in; 1) transformative signaling due to mutation of a tyrosine residue (RP3Y588Fmutant) which prevents the binding of downstream adaptor proteins 2) inflammatory signaling through mutation of binding sites for TRAF2 and TRAF6. Transformation only RP3 mutants grew tumors in immunodeficient and immunocompetent mice, strengthening our hypothesis that the inflammatory component of RP3 is responsible for the benign nature of PTC.
To assess the impact of inflammatory RP3 on the progression of different tumors, various thyroid and non-thyroid tumorigenic cell lines were transduced with MSCV_IRES_GFP_RP3 mutants and sorted for GFP expression. With highly immunogenic MC57G cells (C57BL/6 mice), the transforming only mutants developed tumors whereas wild type RP3 along with inflammatory only RP3 were rejected. Inflammation only RP3 mutant also led to slower tumor growth in Renca cell line (Balb/c) demonstrating the effect to be independent of haplotype. We are currently extending the analysis to PTC lines with BRAF and KRAS mutations, which are usually associated with more aggressive tumor profiles without an inflammatory tumor microenvironment. Our data so far suggest that contrary to the contemporary view, inflammation can retard tumor progression. Thus, the RP3 oncogene might be exploited in this regard. Future experiments aim to further characterize the importance of RP3-driven inflammation in tumor growth through continued in vivo and in vitro studies.
Citation Format: Suresh C. Kari, Laurence C. Eisenlohr. Impact of RET/PTC3 oncogene's inflammatory and transformative signaling on tumorigenicity of thyroid and non-thyroid tumorigenic cell lines. [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 4077. doi:10.1158/1538-7445.AM2014-4077
Abstract 4081: Id4 (inhibitor of dna binding 4) crosstalk with pten-akt pathway
Authors: Komaragiri Shravan Kumar 
Published: May 2015

Abstract
Introduction: Inhibitor of DNA binding/differentiation protein 4 (Id4), acts as a dominant negative regulator of basic helix loop helix (bHLH) family of transcription factors. Id4 shares the homology of HLH domain with other Ids and lack the basic DNA binding region. Previous studies from our lab had shown that unlike Id1, Id2 and Id3, Id4 acts as a tumor suppressor in prostate cancer by attenuating cell proliferation and promoting apoptosis. In this study we investigated whether Id4 acts as a tumor suppressor by regulating the AKT pathway.
Experimental procedures: Id4 protein expression was analyzed on human prostate adenocarcinoma samples by Immunohistochemistry. We also performed Immunohistochemistry to determine AKT, pAKT, PTEN protein expression in Id4 knockout mouse prostates. In addition we determined the expression levels of the above mentioned proteins in prostate cancer cell lines with or without Id4 (LNCaP, LNCaP-Id4, DU145, DU145+Id4, PC3).
Results: IHC demonstrated decreased Id4 protein expression in human prostate tissue samples whereas higher nuclear Id4 expression was found in normal human and mouse prostate tissues. IHC on Id4 knockout (Id4-/-) mouse prostates demonstrated an increase in pAKT expression, whereas AKT expression did not change significantly when compared to normal mouse prostate. PTEN expression levels decreased ignificantly in Id4 knockout mouse prostates. Similar pattern was observed in prostate cancer cell lines: DU145 cells lacking Id4 had low PTEN as compared to Id4 over-expressing DU145 cells. Id4 expression was also associated with PI3 kinase activity in LNCaP and PC3 cells. These results suggest Id4 regulates AKT-PI3K pathway by attenuating PTEN.
Conclusions: Id4 appears as a potential tumor suppressor gene that exerts its tumor suppressor activity by promoting PTEN expression. PTEN in turn regulates AKT phosphorylation that stabilizes p53, AR and NKX3.1 expression in the normal prostate.
Acknowledgement: The research was supported by NIH/NCI-RO1CA128914 and in part by NIH/NCRR/RCMI G12RR03062
Citation Format: Shravan Kumar Komaragiri. Id4 (inhibitor of dna binding 4) crosstalk with pten-akt 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 4081. doi:10.1158/1538-7445.AM2014-4081
Abstract 4087: Identification of microRNAs involved in shaping immune surveillance and growth properties of tumors
Authors: Seliger Barbara , Jasinski-Bergner Simon , Bukur Juergen , Schulz Kristin , Stehle Franziska 
Published: May 2015

Abstract
Ligands of the natural killer (NK) cells and CD8+ cytotoxic T lymphocyte (CTL) receptors, such as the inhibitory classical HLA-G antigen, are often deregulated upon viral infection and neoplastic transformation thereby allowing virus-infected or malignant-transformed cells to escape NK and T cell-mediated immune surveillance. The underlying molecular mechanisms controlling the aberrant HLA-G expression have been recently identified suggesting that cellular microRNAs (miRs) target the 3′UTR of HLA-G mRNA thereby shaping the anti-tumoral immune response. Functional analysis of these miRs demonstrated an inverse correlation of HLA-G and miR expression, which was directly associated with tumor grading, staging, disease progression and survival of renal cell carcinoma patients. Furthermore, these miRs enable tumors to evade NK and T cell cytotoxicity. Using 2DE-based proteome analysis in combination with MALDI-TOF mass spectrometry of HLA-G-specific miR transfectants and control cells lead to the identification of novel targets of these miRs including the 14-3-3-β protein (YWHAB). The miR-regulated YWHAB expression not only alters tumor cell proliferation, but also the sensitivity to apoptosis. Loss of HLA-G-specific miRs enhanced YWHAB expression, which is accompanied by an inhibition of pro-apoptotic gene expression leading to apoptosis resistance, enhanced proliferation, migration and tumor progression. Furthermore, YWHAB expression and lack of HLA-G-specific miR expression directly correlate with a worse clinical outcome of HLA-G+ tumors linking for the first time tumor immune escape mechanisms with the malignant phenotype. Thus, the HLA-G-regulating miRs not only affect immune surveillance, but also enhance tumorigenicity.
Citation Format: Barbara Seliger, Simon Jasinski-Bergner, Juergen Bukur, Kristin Schulz, Franziska Stehle. Identification of microRNAs involved in shaping immune surveillance and growth properties of tumors. [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 4087. doi:10.1158/1538-7445.AM2014-4087
Abstract 4088: Methylselenic acid inhibits the soluble and cell-surface bound NKG2D-ligand ULBP2 in melanoma
Authors: Uhlenbrock Franziska K. , Jensen Michael Hagemann , Kehlet Stephanie , Andresen Lars , Skov Søren 
Published: May 2015

Abstract
The secretion of the soluble NKG2D-ligand ULBP2 is a marker for poor prognosis in several types of cancer. NKG2D-ligands are normally directed to the cell surface of stressed, inflamed or pre-cancer cells and serve as targets for immune effector cells expressing the NKG2D receptor. The soluble NKG2D-ligands are devastating due to their chronic activation and thereby desensitization of NKG2D expressing immune effector cells. In fact this leads to severely compromised immune activation governing cancer development.
The present study describes that methylselenic acid (MSA) is able to inhibit soluble ULBP2 in different primary melanoma cell lines. Moreover, MSA actively suppressed ULBP2 both from constitutively expressing tumors and after induction by HDAC-inhibitors. In the attempt to elucidate the mechanism of inhibition, real-time qPCR experiments were performed. MSA activated the promoter and the transcription of the ULBP2 gene at a level similar to HDAC-inhibitors. These findings strongly indicate that ULBP2 is post-transcriptional regulated.
Selective blocking of ULBP2 from melanomas or other cancers that produces soluble immune suppressive ULBP2 is thus a new treatment strategy that also has the potential to be used in combination with existing treatment regimens.
Citation Format: Franziska K. Uhlenbrock, Michael Hagemann Jensen, Stephanie Kehlet, Lars Andresen, Søren Skov. Methylselenic acid inhibits the soluble and cell-surface bound NKG2D-ligand ULBP2 in melanoma. [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 4088. doi:10.1158/1538-7445.AM2014-4088
Abstract 409: Regulation of chromatin remodeling in leukemia by Ikzf1 and Casein Kinase II
Authors: Payne Jonathon L. , Casiano Carlos M. , Payne Kimberly J. , Sloane Justin , Dovat Elanora , Song Chunhua , Dovat Sinisa 
Published: May 2015

Abstract
Ikzf1 (Ikaros) encodes a zinc finger protein that binds DNA and regulates gene expression via chromatin remodeling. The loss of Ikaros activity due to genetic or functional inactivation results in leukemia with a poor prognosis. The goal of our project is to determine the mechanism by which Ikaros regulates chromatin remodeling in human leukemia. Previous studies showed that Ikaros function in leukemia is controlled through its direct phosphorylation by Casein Kinase II (CK2). Treatment of leukemia cells with CK2 inhibitors results in enhanced Ikaros activity, which leads to cessation of cell growth. We have studied the mechanism by which inhibition of CK2 regulates Ikaros-induced epigenetic changes in leukemia. The human Nalm6 pre-B cell leukemia was treated with CK2 inhibitor, and the epigenetic signature of the histone modifications H3K9ac and H3K9me3 were determined using chromatin immunoprecipitation coupled with next generation sequencing (ChIP-SEQ). H3K9ac histone modification is associated with positive regulation of gene expression, while H3K9me3 is associated with the formation of heterochromatin and repression. The enrichment of particular histone modifications was confirmed by quantitative chromatin immunoprecipitation (qChIP). The results demonstrated that the inhibition of CK2 activity in leukemia results in a marked alteration in the epigenetic signature of both H3K9ac and H3K9me3 compared to untreated cells. This is associated with altered Ikaros binding to its target genes following CK2 inhibition. Current bioinformatics analysis is directed toward establishing a link between epigenetic modifications and Ikaros binding in leukemia. These results suggest that CK2 and Ikaros regulate gene transcription via epigenetic modifications and chromatin remodeling in leukemia.
Citation Format: Jonathon L. Payne, Carlos M. Casiano, Kimberly J. Payne, Justin Sloane, Elanora Dovat, Chunhua Song, Sinisa Dovat. Regulation of chromatin remodeling in leukemia by Ikzf1 and Casein Kinase II. [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 409. doi:10.1158/1538-7445.AM2014-409