bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1939: Association between LRRK2 and 4E-BP1 protein levels in normal and malignant cells
Authors: Pons Berta , Armengol Gemma , Ramón y Cajal Santiago J. 
Published: August 2014

Abstract
Translational control is a crucial component of cancer development and progression. Eukaryotic initiation factor 4E (eIF4E) mediates eIF4F association with the mRNA 5’ cap structure to stimulate cap-dependent translation initiation. The eIF4E-binding protein, 4E-BP1, regulates cap-dependent translation through its phosphorylation at multiple sites. The search for new kinases that could be implicated in 4E-BP1 phosphorylation, and determination of the mechanisms that affect 4E-BP1 stability are important to understand the role of eIF4E in cell transformation.
In this study, we investigate 48 kinases that may be implicated in 4E-BP1 phosphorylation and stability. The screening study was based on analysis of 4E-BP1 status after inhibition of these kinases in a breast carcinoma cell line (MDA-MB 231 cells).
With the use of this method, several kinases that affect 4E-BP1 stability (LRRK2, RAF-1, p38γ, GSK3β, AMPKα, PRKACA and PRKACB) and 4E-BP1 phosphorylation (CDK1, PDK1, SRC, PRKCB1, PAK2, p38β PRKCA and CaMKKB) were identified. These novel findings provide evidence that 4E-BP1 can be regulated and stabilized by multiple kinases implicated in several cell signaling pathways. We also found that LRRK2 downregulation affects 4E-BP1 stability and causes degradation of this factor in various cell types. Interestingly, inhibition of proteasome activity by MG132 restored total 4E-BP1 protein levels in cells where LRRK2 was downregulated. In addition, these stabilization events appear to be functionally important for cell growth control in normal cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1939. doi:10.1158/1538-7445.AM2011-1939
Abstract 194: The Golgi/ER protein p23/Tmp21 regulates PKCΔ-mediated apoptosis in prostate cancer cells
Authors: Wang Hongbin , Xiao Liqing , Kazanietz Marcelo G. 
Published: August 2014

Abstract
Protein kinase C isozymes have prominent and specific roles in the control of apoptosis and survival of cancer cells. Activation of PKCΔ in androgen-dependent prostate cancer cell models triggers an apoptotic response that is mediated by the release of death factors and the activation of the extrinsic apoptotic cascade. We have previously established that p23/Tmp21, a member of the p24 family ER/Golgi cargo protein, physically interacts with the C1 domains in PKC isozymes and regulates the their activation. Here we found that depletion of p23/Tmp21 significantly potentiates apoptosis induced by phorbol 12-myristate 13-acetate (PMA) in LNCaP prostate cancer cells and the DNA damaging agent doxorubicin. The potentiation of the PMA effect was prevented by the pan-PKC inhibitor GF 109203X or PKCΔ RNAi depletion. Yeast two-hybrid assay revealed that the PKCΔC1a-b domain interacts with p23/Tmp21. In addition, co-localization analysis by confocal microscopy demonstrated that GFP-PKCΔ C1b domain co-localizes with p23/Tmp21 in the perinuclear region. The interaction of PKCΔ and p23/Tmp21 in LNCaP cells was also confirmed by co-immunoprecipitation. Interestingly, disruption of PKCΔ-p23/Tmp21 association by depletion of p23/Tmp21 in LNCaP cells significantly accelerated PMA-induced PKCΔ translocation to the plasma membrane and potentiates the activation of PKCΔ downstream effectors ROCK and JNK. Moreover, a mutated PKCΔ that is unable to interact with p23/Tmp21 triggered significant apoptotic effect when expressed in LNCaP cells. In summary, our data provide evidence that p23/Tmp21 acts as an anchoring protein that retains PKCΔ at the perinuclear region, thus limiting its availability for signaling.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 194. doi:10.1158/1538-7445.AM2011-194
Abstract 1942: Lactoferrin interferes with the Akt-GSK3b-cyclin D1 growth signaling of human prostate cancer cells
Authors: Banerjee Partha , Jagadeesh Shankar , Dobi Albert , Srivastava Shiv 
Published: August 2014

Abstract
The etiology of human prostatic carcinoma remains largely undefined. However, it is becoming clear that epigenetic inactivation of various tumor suppressor genes could play pivotal role in the development of various cancers including prostate cancer. One of such tumor suppressor is lactoferrin (LTF) gene.
Epigenetic inactivation of LTF may contribute to the development of human prostate cancer. Ectopic expression of LTF or supplementation of bovine LTF in human prostate cancer cells that lack endogenous LTF expression resulted in reduced growth in vitro supporting a role for LTF as a putative tumor suppressor gene. Therefore, it is important to delineate the molecular mechanisms by which LTF regulates prostate cancer cell growth.
In this investigation, we demonstrated that, purified bovine LTF treatment of LNCaP and PC3 cells blocked cell cycle progression and up-regulated cell cycle inhibitors, p15 (INK4b), p16 (INK4a), p21 (Cip1) and p27 (Kip1) and p57 (Kip2) in a dose dependent manner. As a consequence, Cdk4, Cdk6, cyclin D1 and cyclin E levels decreased significantly with bovine LTF treatment. Subsequently, LTF treatment decreased nuclear cyclin D1 and possibly facilitated its degradation. In order to examine the degradation of cyclin D1, we analyzed the levels of phospho-Akt-Ser473- and phospho-Akt-Thr308 after LTF treatment of LNCaP and PC3 cells. We observed that LTF dose dependently decreased phospho-Akt-Ser-473 and phospho-Akt-Thr-308 without altering the total Akt levels. As a consequence, activated GSK3-beta level increased, which is a known to degrade cyclin D1.
In summary, this study shows that bovine LTF treatment can inhibit human prostate cancer cell growth by disrupting Akt-GSK3b-cyclin D1 signaling pathway. Lactoferrin, therefore, promises an encouraging therapeutic potential for prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1942. doi:10.1158/1538-7445.AM2011-1942
Abstract 1944: Phospholipid scramblase 1 and 3 as novel effectors of cripto-1 signaling
Authors: Karasawa Hideaki , Nagaoka Tadahiro , Rangel Maria Cristina , Castro Nadia P. , Held Natalie , Gonzales Monica , Bianco Caterina , Salomon David S. 
Published: August 2014

Abstract
In the present study we performed a yeast two-hybrid (Y2H) screen to search for novel Cripto-1 (CR-1) binding proteins that might modulate CR-1-dependent signaling pathways involving Nodal/Gdf3/Smad 2/3 or GRP78/glypican-1/c-src. Screening a mouse embryo or human colon cDNA prey library with a peptide sequence of CR-1, we isolated six candidate genes, including mNotch3, mFibulin-4, mCHD4, hAHNAK, hHUWE1 and mouse phospholipid scramblase 3 (PLSCR3). PLSCRs consist of a family of four related genes that encode for endofacial transmembrane proteins, and have been proposed to play a role in the redistribution of plasma membrane phospholipids. Recent work on the PLSCRs has revealed their involvment in signal transduction and lipid metabolism. The most studied member of this family, PLSCR1, has been shown to partition into lipid rafts implicated in the regulation and endocytic trafficking of receptor-signaling complexes. We confirmed the results of the Y2H screen since we found that full-length GFP-tagged PLSCR1 and PLSCR3 were able to bind to 3xFLAG-CR-1 in transiently transfected 293T cells, as detected by coimmunoprecipitation and Western blot analysis. In addition, we were able to detect co-localization of these proteins in 293T cells that were transiently expressing GFP-PLSCR1/3 and 3xFLAG-CR-1 by immunocytochemistry. We then evaluated the effect of interaction between CR-1 and PLSCR-1/3 on Nodal signaling. We therefore analyzed the activity of the Nodal/Activin-responsive (n2)7-luciferase reporter ((n2)7-Luc), which contains mouse Fast-1 binding sites from the Nodal left side-specific enhancer, in 293T cells transiently expressing CR1-FLAG, PLSCR1-GFP, PLSCR3-GFP, (n2)7-Luc, TK-renilla, mouse Fast-1, mouse Nodal and human ALK4 expression vectors. Overexpression of PLSCR1 induced a very strong dose-dependent inhibition of CR-1 activation of Nodal-responsive luciferase reporter activity in 293T cells. In contrast, overexpression of PLSCR3 did not have a significant inhibitory effect on CR-1activation of Nodal-responsive luciferase reporter activity in 293T cells. The effect of knockdown of PLSCR-1/3 with specific siRNA on CR-1 ability to induce activation of a Nodal-responsive luciferase reporter assay and to modulate CR-1 Smad-dependent and Smad-independent signaling pathways is currently under investigation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1944. doi:10.1158/1538-7445.AM2011-1944
Abstract 1947: FAM129B regulates cell proliferation and activates NF-κB and Nrf2 by inactivating KEAP1 in cancer cells
Authors: Lin You-Chin , Cheng Kai-Chung , Lai Alan Chuan-Ying , Chen Yu-Ju , Yu Alice L. 
Published: August 2014

Abstract
The Family with sequence similarity 129 (FAM129) contains three membrane proteins, FAM129A, B and C. FAM129A (also called Niban) and FAM129C (also called BCNP1) have been found to be up-regulated in thyroid tumors and chronic lymphocytic leukemia, respectively. Although phosphorylation of FAM129B has been suggested to play a role in controlling melanoma cell invasion, the molecular mechanism of FAM129B in tumorigenesis remains largely unknown. In this study, we first identified FAM129B as one of proteins with altered phosphorylation status in breast cancer stem cells by the phosphor-mass spectrum technique. Silencing of FAM129B expression in breast cancer cell line, MDA-MB-231, led to decreased proliferation, along with flattened and rounded cell morphology. By mammalian two-hybrid system and FRET (fluorescence resonance energy transfer) assay, KEAP1 (kelch-like ECH-associated protein 1) was detected to interact with FAM129B. KEAP1 has been reported to function as a substrate adaptor protein for Cul3-dependent E3 ligase complex to repress IKKβ and transcription factor Nrf2. We indeed observed that the expression of NF-κB and Nrf2 downstream genes, FN1 and NQO1, was down-regulated in FAM129B-silenced cells by qPCR analysis. On the other hand, FAM129B together with either IKKβ or Nrf2 synergistically activated NF-κB and Nrf2 promoter activity by reporter assays. Taken together, our results suggest that FAM129B might play an important role in the regulation of cell proliferation in cancers by inactivating KEAP1 which in turn activates Nrf2 and IKKβ activities.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1947. doi:10.1158/1538-7445.AM2011-1947
Abstract 1948: Functional profiling of signal transduction pathway proteins in gastric cancer (GC) patients
Authors: Lee Tani , Lee Jeeyun , Magonova Katya , Kang Won Ki , Harvie Gulia , Barham Robert , Leesman Glen , Kim Phillip , Singh Sharat , Kim Sung 
Published: August 2014

Abstract
Although gastrectomy is the only curative treatment in gastric cancer (GCA) patients, a high recurrence rate ranging from 40 ∼ 60% following curative surgery still accounts for poor overall survival. In order to further improve survival, there is an urgent need to identify reliable molecular prognostic markers for survival or recurrence following adjuvant chemoradiation therapy. With the advent of molecularly targeted therapy in cancer care, profiling of pathway proteins for targeted drug is of utmost importance. Hence, we have developed a multiplexed immunoassay platform for functional profiling of the signal transduction pathway proteins using a multiplexed immuno-microarray platform.
A multiplexed protein microarray platform, Collaborative Enzyme Enhanced Reactive-immunoassay (CEER) that utilizes the formation of a unique immuno-complex requiring co-localization of two detector-antibodies (d-abs) has been utilized to profile targetable biomarkers in 447 fresh frozen tumor tissues procured during surgical procedure from GCA patients with localized disease. The collaboration between two channeling-enzymes conjugated on two d-abs in proximity enables the profiling of the target proteins with extreme sensitivity and specificity in multiplexed fashion. As CEER can also be configured for each specific target protein, it allows differential detection of truncated targets (i.e., p95HER2) from their normal counter parts (i.e., HER2). Here we report the profiling of HER2, p95HER2, HER1, HER3, PI3K, cMET, Shc and IGF1R in GCA for their levels of expression and phosphorylation. Approximately 12% of patients in this cohort expressed high levels of HER2. Varying levels of truncated HER2 were detected in 7.1% (27/447) of GCA pts. HER3 were found in approximately 40% of pts. The prevalence of biomarker expression/activation along with the outcome of unsupervised clustering analysis of signaling molecules revealing diverse and distinct disease subtypes will be presented.
The treatment of recurrent or metastatic GC may be optimized based on patient-specific functional profiling of biomarker leading to patient-tailored treatment strategies. In addition, the incidence of alteration in transduction pathway proteins may guide oncologists for further clinical development of targeted therapies or combined / sequenced targeted therapies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1948. doi:10.1158/1538-7445.AM2011-1948
Abstract 1954: In vitro effects on gene expression of Casp9, GRB10, and CDKN1B following rG3 treatment of human breast cancer cells
Authors: Schalkoff Katie , Walker Heather , Scott Tom 
Published: August 2014

Abstract
Introduction: Integrins can stimulate cellular growth and proliferation, as well as apoptosis, and are important factors in AKT cell signaling. To assess their binding, a recombinant protein of the G3 domain of laminin-5 (rG3) that specifically binds the alpha subunit expressed on metastatic MDA-MB-231 cells in vitro was produced. Studying changes in expression of genes involved in cell signaling and the apoptosis cascade, specifically CDKN1B, GRB10, and Caspase 9, can help improve understanding of signaling pathways of metastatic cells and the AKT pathway.
Methods: rG3 was produced using ArcticExpress Competent Cells (Stratagene). Plasmid DNA was transformed into competent cells and transferred to ampicillin plates for colony production of successful transformation. A single colony was used to inoculate LB broth containing gentamycin and ampicillin for an overnight incubation at 37°C. LB without antibiotics was inoculated with the overnight culture and incubated at 30°C for 3 hours. The temperature was lowered to 11.5°C before the expression was induced using IPTG at a final concentration of 1mM. SDS-PAGE/immunoblotting confirmed successful soluble rG3 protein expression. MDA-MB-231 human breast cancer cells from ATCC were grown in tissue culture flasks and maintained until confluent. Cells were plated at 3 × 106 cells/well in a 6-well tissue culture plate in a 2 ml volume of DMEM without pen/strep in duplicate. rG3 was added to wells at a final concentration of 175 µg/ml for treated cells and corresponding control buffer for untreated cells. After incubation overnight, cells were collected at time points within 0-60 hours and RNA was isolated using Qiagen RNeasy. An eppendorf Realplex 96-well plate reader was used for PCR analysis using a β-actin standard curve. Differences in gene expression were shown in fold change using Pfaffl's Method.
Results: Our preliminary data show there are changes in gene expression after treatment with rG3.We are further investigating these changes in expression. Preliminary results suggest that changes in gene expression after treatment may be informative in understanding the AKT signaling pathway.
Conclusion: The study of these changes in gene expression after altering the AKT pathway from treatment with rG3 could prove to be a helpful tool in understanding the signaling mechanisms of metastatic cells and the details of the signaling pathways involved in apoptosis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1954. doi:10.1158/1538-7445.AM2011-1954
Abstract 1956: Enhanced colony-forming ability, and motility and migratory properties of Cisplatin-resistant ovarian cancer cells
Authors: Yue Peibin , Zhang Xiaolei , Turkson James 
Published: August 2014

Abstract
Ovarian cancer causes the highest gynecologic neoplasm-related deaths in the United States. Although the majority of ovarian cancer patients respond to Cisplatin therapy, most develop recurrent and resistant disease, raising the need to understand the molecular mechanisms that support the resistant phenotype and to identify novel effective therapeutic and chemo-sensitizing modalities. In this study, we developed Cisplatin resistance in vitro to address the molecular and biological mechanisms that may be presented by the recurrent disease. The resistant lines, A2780S/CP3 and A2780S/CP5, which were derived from the Cisplatin-sensitive line, A2780S and are resistant to 3 and 5 μM Cisplatin, respectively, showed marked changes in morphology, compared to the parental cells. Notably, both resistant lines showed enhanced colony-forming ability and significantly enhanced cell motility and migratory properties. Molecular mechanistic analysis indicated the Cisplatin resistance was associated with hyperactive epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase (Erk)1/2MAPK and EGFR-Signal Transducer and Activator of Transcription (Stat)3 pathways, the overexpression of Survivin and vascular endothelial growth factor receptor (VEGF), and F-actin and Cortactin, with F-actin localization that is predominantly at the cellular extensions. Treatment of the Cisplatin-resistant A2780S/CP5 line with the EGFR inhibitor, Iressa or the Stat3 inhibitor, S3I-201 inhibited the colony-forming ability of these cells, without suppressing their viability, suggesting EGFR-Erk1/2 and EGFR-Stat3 activation are required for the proliferation of the resistant cells. Furthermore, inhibition of EGFR or Stat3 activation significantly suppresses the migration of A2780S/CP3 cells, while the motility of both A2780S/CP3 and A2780S/CP5 lines are sensitive to EGFR inhibition. These results together suggest that Cisplatin resistance in ovarian cancer is mediated in part through the activation of the EGF receptor-mediated Erk and Stat3 pathways that promote increased cell proliferation, motility and migration. These findings raise the possibility that EGFR or Stat3 inhibitors combined with Cisplatin may be an effective therapeutic approach for Cisplatin-resistant ovarian cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1956. doi:10.1158/1538-7445.AM2011-1956
Abstract 1957: PMEPA1 promotes androgen receptor negative prostate cell proliferation through suppressing the Smad3/4-c-Myc-p21Cip1 signaling pathway
Authors: Liu Rong , Zhou Zhongmei , Huang Jian , Chen Ceshi 
Published: August 2014

Abstract
The PMEPA1 gene has been shown to suppress the androgen receptor (AR) and TGFβ signaling pathways and is abnormally expressed in prostate tumors. However, the role and mechanism action of PMEPA1 in AR-negative prostate cancer are unclear. Here, we demonstrate that inhibition of PMEPA1 suppresses AR-negative RWPE1 and PC-3 prostate cell proliferation through upregulating the p21 transcription. Additionally, PMEPA1 overexpression suppresses the p21 expression and promotes cell proliferation. PMEPA1 is induced by TGFβ as a negative feedback loop to suppress Smad3 phosphorylation and nuclear translocation, upregulates c-Myc, downregulates p21, and promotes PC-3 cell proliferation. The PMEPA1 functions depend on its Smad2/3 binding motif. Consistently, depletion of Smad3/4, but not Smad2, blocks the PMEPA1's functions of regulating c-Myc and p21. Importantly, stable depletion of PMEPA1 in PC-3 inhibits xenograft growth. Finally, we found that PMEPA1 is overexpressed in a subset of prostate cancer cell lines and tumors. These findings suggest that PMEPA1 may promote AR-negative prostate cancer cell proliferation through p21. (This work was supported by a grant from the Department of Defense (W81XWH-07-1-0191) and a grant from the American Cancer Society (RSG-08-199-01). Dr. Liu is supported by a postdoctoral fellowship from American Urological Association Foundation.)
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Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1957. doi:10.1158/1538-7445.AM2011-1957
Abstract 1967: Ligand-dependent TGFβ signalling potential
Authors: McLean Sarah E. , Guglielmo John Di 
Published: August 2014

Abstract
Transforming growth factor beta (TGFβ) is a cytokine which regulates many normal biological processes such as organogenesis and cell cycle control. Its signaling pathway is under intense study as it is commonly dysregulated in pathophysiological conditions such as cancer and fibrosis. The TGFβ signalling cascade is initiated by the binding of ligand to cell-surface serine-threonine kinase receptors. Binding of ligand to the TGFβ receptors initiates phosphorylation of intracellular signalling proteins called Smads, which can then enter the nucleus and initiate specific transcriptional programs. There are three TGFβ ligands which can activate canonical Smad signalling: TGFβ1, TGFβ2 and TGFβ3. These ligands share significant sequence homology (70-80%) but have different spatial and temporal patterns of expression in development. Although TGFβ1 and TGFβ3 are highly expressed in the tumour microenvironment, the role of TGFβ3 has been largely over-looked and thought to be the same as TGFβ1. The objective of the present study is to evaluate the signalling capacity of TGFβ1 and TGFβ3 in non-small cell lung cancer cells. Using dose response studies, we show that TGFβ1 ligand induces Smad2 phosphorylation to a greater extent than TGFβ3. We also show that TGFβ3 induces a lower reduction in steady-state levels of E-cadherin, a protein involved in cell-cell adhesion, compared to TGFβ1. To evaluate the transcriptional programs of both ligands, we used microarray technology to assess gene transcription in non-small cell lung cancer cells treated with TGFβ1 or TGFβ3. Consistent with our signalling data, we found that TGFβ3 induces far fewer genes than TGFβ1. Future studies will evaluate the differential roles of TGFβ1 and TGFβ3 in cancer cell migration and epithelial-to-mesenchymal transition.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1967. doi:10.1158/1538-7445.AM2011-1967