bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1051: Atypical PKC and TGFβ receptors co-operate to phosphorylate Par6
Authors: Gunaratne Adrian , Guglielmo John Di 
Published: June 2012

Abstract
Transforming growth factor beta (TGFβ) is involved in many aspects of cellular behavior including apoptosis and differentiation. In tumor cells, TGFβ signaling alters cell plasticity through a loss in apical-basal cell polarity and induces epithelial to mesenchymal transition (EMT). Integral to this process is the phosphorylation of a polarity protein, Par6, on a conserved serine residue (S345). Recent work has shown that phosphorylation of this site not only increases cell plasticity and EMT, but also promotes an invasive phenotype in breast cancer cells. Our work suggests that a polarity partner of Par6, atypical Protein Kinase C (aPKC), can also phosphorylate Par6 on this critical site to drive distinct cellular changes in non-small cell lung cancer (NSCLC) cells. Using co-immunoprecipitation studies and immunofluorescence microscopy, we show that aPKCι interacts with TGFβ receptors through the adaptor Par6, and that these proteins localize to the leading edge of migrating cells. Furthermore, co-expression of Par6 with TGFβ receptors results in increased phospho-Par6 levels as previously reported. However, we have also found that phosphorylation of Par6 increases in the presence of aPKC. aPKC kinase activity as well as association with Par6 were found to be important for Par6 phosphorylation as evidenced by a loss in phospho-Par6 using a kinase deficient mutant of PKCζ (PKCζ -KR) as well as a mutant of Par6 that does not bind aPKC (Par6-K19A). Furthermore, gene silencing of atypical PKC reduces TGFβ induced cell morphology changes, E-cadherin loss, and stress fiber production. Finally, gene silencing of atypical PKC was observed to reduce TGFβ dependent migration of NSCLC cells. In conclusion, our results indicate that atypical PKC cooperate with TGFβ receptors to regulate phospho-Par6 levels to drive an invasive phenotype of NSCLC cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1051. doi:10.1158/1538-7445.AM2011-1051
Abstract 1055: Effect of embryonic stem (ES) cell-conditioned microenvironment on the reprogramming of melanoma
Authors: Kim Myoung Ok , Kim Sung-Hyun , Jeong Chul-Ho , Lee Kun-Yeong , Yao Ke , Bode Ann M. , Cho Yong-Yeon , Bowden Tim G. , Dong Zigang 
Published: June 2012

Abstract
The cancer micro-environment affects cancer cell proliferation and growth. Embryonic stem (ES)-preconditioned 3-dimensional (3-D) culture of cancer cells induces cancer cell reprogramming and results in a change in cancer cell properties such as differentiation and migration in skin melanoma. However, the mechanism has not yet been clarified. Using the ES-preconditioned 3-D micro-environmental model, we provide evidence showing that the ES micro-environment inhibits proliferation and anchorage-independent growth of SK-MEL-5 and SK-MEL-28 human melanoma cells, which is accompanied by the down-regulation of c-jun and c-fos gene expression. We also found that the ES micro-environment suppresses telomerase activity and thereby induces senescence in SK-MEL-5 and SK-MEL-28 cells. Furthermore, we observed that gremlin, an antagonist of bone morphogenic protein 4 (BMP4), is secreted from ES cells and plays an important role in cellular senescence. Taken together, these results demonstrated that gremlin is a crucial factor responsible for abrogating cancer properties in the ES-preconditioned 3-D micro-environment.
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 1055. doi:10.1158/1538-7445.AM2011-1055
Abstract 1063: BRAFV600E status predicts higher uPA levels in papillary thyroid cancer
Authors: Darr E. Ashlie , Nowicki Theodore S. , Kummer Nicolas , MacEwan Melanie , Dunbar Julie , Suslina Nina , Iacob Codrin , Shin Edward , Schantz Stimson , Tiwari Raj , Geliebter Jan 
Published: June 2012

Abstract
Of the 44,670 new cases of thyroid cancer predicted for this year in the US by the American Cancer Society, 80% will be papillary thyroid carcinoma (PTC). PTC typically arises from a gain-of-function mutation in the RET, RAS, or BRAF genes which make up a linear signaling cascade for ERK activation in over 90% of PTC cases. PTCs possessing the BRAFV600E mutation have been associated with greater local invasion and regional metastatic potential. Urokinase plasminogen activator (uPA) has been shown to be an important mediator of invasion and metastasis in several cancers. To determine the extent to which BRAFV600E mutation status predicts up-regulation of the uPA in PTC, a study using patient thyroid tissue samples obtained over a 6-year period at a single tertiary care center was undertaken. DNA and RNA were obtained from patient PTC and matched, normal thyroid tissue samples using the Trizol method. BRAFV600E mutational status of the DNA was determined using the TaqMan SNP genotyping assay, while RNA was analyzed for differences in uPA transcription levels (relative to matched, normal thyroid tissue) by qRT-PCR. Fifty-four percent of the PTC samples possessed the BRAFV600E mutation. PTC samples bearing the BRAFV600E mutation displayed significantly higher uPA RNA levels (relative to matched control tissue) than those samples with wild-type BRAF (5.883 vs. 1.27-fold, p&lt;0.05, Wilcoxon signed-rank test). Additionally, uPA RNA levels were significantly higher in patients with nodal metastasis (p&lt;0.05). These data provide new evidence of the roles of BRAFV600E and uPA in PTC invasive pathology and demonstrate for the first time that BRAFV600E status is able to predict higher uPA levels in PTC.
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 1063. doi:10.1158/1538-7445.AM2011-1063
Abstract 107: miR-200a targets SIRT1 for malignant transformation
Authors: Eades Gabriel , Yao Yuan , Zhou Qun 
Published: June 2012

Abstract
Evidence supports a critical role for microRNAs in regulation of tissue specific differentiation and development. Signifying a disruption of these programs, miRNA profiling has revealed extensive dysregulation in tumors compared with healthy tissue. The malignant contribution of some miRNAs is understood, however, in other instances the pathways affected by aberrant miRNA expression have yet to be characterized. The miR-200 family has been established as a key regulator of epithelial phenotype and as such, is deeply involved in EMT-like processes in cancer. While exploring a model of transformation of normal mammary epithelium we observed epigenetic silencing of the miR-200 family- as was previously identified in breast cancer cell lines. Here we show the class III histone deacetylase SIRT1 overexpression in a TGF-β driven model of transformation as well as in patient samples of early stage breast cancer. We establish SIRT1 transcript as subject to novel regulation of the miR-200 family, through miR-200a / miR-141 targeting. Moreover, we demonstrate that downregulation of miR-200 family members contributes at least in part to the overexpression of SIRT1, a proposed oncogene in breast cancer. Restoration of miR-200a or knockdown of SIRT1 results in decreased growth in soft agar and decreased invasion. These observations provide further evidence of the important tumor suppressive role of miR-200 family members in breast epithelium, as well as identifying a novel regulatory mechanism that may contribute to SIRT1 upregulation early in breast tumorigenesis.
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 107. doi:10.1158/1538-7445.AM2011-107
Abstract 1070: Pancreatic Ductal Adenocarcinoma (PDA) mice lacking Mucin 1 has a profound defect in tumor growth and metastasis
Authors: Besmer Dahlia , Roy Lopamudra Das , Curry Jennifer , Tinder Teresa , Manouchehrabadi Mahnaz , Schettini Jorge , Hwang Sunil , Lee Yong-Yook , Gendler Sandra , Mukherjee Pinku 
Published: June 2012

Abstract
MUC1 is over expressed and aberrantly glycosolated in &gt;60% of pancreatic ductal adenocarcinomas. Over expression of MUC1 in pancreatic cancer is known, however the functional role has yet to be fully elucidated due to a dearth of appropriate models. In the present study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1 null (KCKO) or express human MUC1 as a self antigen (KCM). We show that PDA mice lacking Muc1 have significantly slower tumor progression, with tumor weight reaching up to a third of the KCM tumor and half of KC tumor. One out of 10 KCKO mice developed secondary metastasis versus 6 out of 10 and 3 out of 10 KCM and KC respectively. Cell lines derived from KCKO tumors have significantly lower tumorigenic capacity compared to cells derived from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared to mice bearing the KCM tumors. In vitro, the KCKO cells have reduced proliferation and invasion compared to KCM cells and failed to respond to exogenous epidermal growth factor (EGF), platelet-derived growth factor (PDGF), or matrix metalloproteinase-9 (MMP9) stimuli. Further, significantly fewer KCKO cells entered the G2M phase of the cell cycle compared to the KCM cells, consequently more KCKO cells were observed at the S-phase of the cell cycle. Proteomics and western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of MAPK, as well as a significant decrease in Nestin and Tubulin α-2 chain expression in KCKO cells. Treatment of the KCM cells with a MEK1/2 inhibitor, U0126, completely abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, strongly suggesting that MUC1 is necessary for MAPK activity and downstream oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse in order to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro.
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 1070. doi:10.1158/1538-7445.AM2011-1070
Abstract 1071: Repression of ERK1/2 signaling by RanBPM
Authors: Atabakhsh Elnaz , Schild-Poulter Caroline 
Published: June 2012

Abstract
Ran binding protein-M (RanBPM, also called RanBP9) is a nucleo-cytoplasmic protein that has been implicated in a multitude of cellular roles, including the regulation of transcription, protein modifications and stability, and extracellular receptor signaling pathways. However the precise mechanism by which RanBPM functions within the cell remains largely unknown. Previous studies in our lab have identified RanBPM as a pro-apoptotic protein that mediates its effects through modulation of Bcl-2 levels. Here we present evidence that the effect of RanBPM on apoptosis is mediated, at least in part, through regulation of the ERK1/2 signaling pathway.
First, we determined that in addition to Bcl-2, RanBPM also regulated the expression of a second anti-apoptotic factor, Bcl-XL. siRNA-mediated knockdown of RanBPM expression led to elevated Bcl-2 and Bcl-XL mRNA expression, suggesting regulation by RanBPM at the transcriptional level. Conversely, we found that expression of RanBPM also affected ectopically expressed Bcl-2 protein levels. Together, these findings suggested that RanBPM regulated the expression of Bcl-2 and Bcl-XL at both the transcriptional and post-translational levels.
One pathway that has previously been shown to regulate the expression of Bcl-2 and Bcl-XL at both the transcriptional and post-translational levels is the ERK1/2 signaling pathway. We found that RanBPM-deficient cells exhibited enhanced ERK1/2 phosphorylation and activation, while re-expression of RanBPM led to a marked decrease in the levels of phosphorylated ERK1/2. Further analyses indicated that enhanced ERK1/2 activation in RanBPM-deficient cells contributed to the elevated levels of Bcl-2 expression observed in these cells, as inhibition of ERK1/2 activation correlated with decreased Bcl-2 protein expression. These findings suggested that RanBPM acts as a novel negative regulator of ERK1/2 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 1071. doi:10.1158/1538-7445.AM2011-1071
Abstract 1085: Nuclear localization and function of EphB4 in prostate cancer cells
Authors: Mertens-Walker Inga , Burke Leslie , Herington Adrian C. , Stephenson Sally-Anne 
Published: June 2012

Abstract
EphB4 is a member of the largest group of receptor tyrosine kinases. EphB4 is significantly overexpressed in prostate cancer where it contributes to tumour progression as demonstrated through knock down of EphB4 in both in vitro and in vivo cell models. EphB4's interaction with its preferred ligand ephrin-B2 may lead, in some cases, to tumour suppression, suggesting therefore that ligand-independent effects are oncogenic. EphB4 is usually located to the plasma membrane, but using an in-house specific monoclonal antibody we have identified EphB4 in the nucleus of prostate cancer cell lines and patient tumour samples. Accordingly, we hypothesise that EphB4 can directly regulate gene expression in prostate cancer cells and that this may be at least one mechanism through which the ligand-independent effects on tumour progression may be manifested. Using chromatin immunoprecipitation with the specific EphB4 antibody we were able to precipitate numerous DNA sequences that are currently being validated. Using confocal microscopy we have discovered that EphB4 colocalises with SUMO-1 (small ubiquitin-like modifier-1). SUMOylation is a posttranslational modification by which one or multiple SUMO molecules are attached to certain lysine residues of a target protein and this can result in cytoplasmic-nuclear shuttling. In silico analysis of EphB4 revealed that it contains a highly conserved potential sumoylation site, K616. This is a highly novel and significant finding in the Eph receptor field and may provide a mechanism by which EphB4 localises to the nucleus. Further characterisation of EphB4 sumoylation and nuclear translocation is currently being undertaken. This study provides novel insight into Eph receptor biology and may identify a major new mechanism by which EphB4 can control gene expression and potentially influence cancer progression.
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 1085. doi:10.1158/1538-7445.AM2011-1085
Abstract 1099: Aza-derivatives of resveratrol are potent inhibitors of macrophage migration inhibitory factor (MIF)
Authors: Fujita Yoshihiko , Islam Rafiqul Islam , Kimura Hideharu , Matsumoto Kazuko , Furuta Kazuyuki , Nagai Tomoyuki , Kudo Kanae , Kaneda Hiroyasu , Tamura Daisuke , Sakai Kazuko , Aomatsu Keiichi , Arao Tokuzo , Okawara Tadashi , Nishio Kazuto 
Published: June 2012

Abstract
Resveratrol (3, 4’, 5-trihydroxy-trans-stilbene), a natural phytoalexin found in grapes and wine, has an anti-proliferative activity in human-derived cancer cells. In our study, we used a conventional condensation reaction between aldehydes and amines to provide a number of aza-resveratrol (3, 4’, 5-trihydroxy-trans- aza-stilbene) derivatives in an attempt to screen for compounds with resveratrol's action but with increased potency. Aza-resveratrol and its hydroxylated derivative (3, 4, 4’, 5-tetrahydroxy-trans- aza-stilbene) showed a more enhanced anti-proliferative effect than resveratrol in an MCF-7 breast carcinoma cell line. To identify the cellular targets of the aza derivatives of resveratrol, we conjugated the latter aza-stilbene compound with epoxy-activated agarose and performed an affinity purification. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, was identified as a major target protein in MCF-7 cell lysates using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS). The aza-resveratrol and its hydroxylated derivative, but not resveratrol, were also found to be potent inhibitors of MIF tautomerase activity, which may be associated with their inhibitory effects on MIF bioactivity for cell growth. Such inhibitors may lead to the development of drugs for the treatment of cancer and, possibly, inflammatory and autoimmune diseases.
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 1099. doi:10.1158/1538-7445.AM2011-1099
Abstract 1102: c-Kit regulates stem-like phenotype and chemoresistance in ovarian cancer cells
Authors: Chau Wing Ka , Wong Alice Sze Tsai 
Published: June 2012

Abstract
One emerging concept of the development of drug-resistant tumors involves a pool of self-renewing malignant progenitors. However, the factors and molecular mechanisms that govern this process remain largely elusive. It has been reported that the high malignancy of these cells is associated with a more efficient cytokine network. In this study, we characterized tumor-initiating cells (TIC) from human ovarian cancer cell line as a model. In contrast to non-TIC, TIC had higher colony formation ability in vitro and greater tumorigenicity in vivo, suggesting that TIC enrich cancer stem-like cells. Notably, the c-Kit receptor tyrosine kinase and its ligand stem cell factor were significantly elevated in TIC. The use of c-Kit siRNA or small molecule inhibitor imatinib to inhibit c-Kit expression and kinase activity, respectively, in TIC resulted in diminished cell proliferation and survival and in vivo tumorigenicity, confirming that the effect was c-Kit specific. Furthermore, we showed that while the two front-line chemotherapeutic drugs cisplatin and paclitaxel could eliminate non-TIC, it had no effect on TIC. Combining cisplatin/paclitaxel with c-Kit siRNA or imatinib prevented the growth of both tumor cell populations. These effects were found to be dependent on signaling of phosphatidylinositol 3-kinase/Akt, but not extracellular signal-regulated kinase 1/2. These results reveal an important role for c-Kit in regulation of self-renewal and proliferation of ovarian cancer cells, which could be selectively targeted for improved treatment.
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 1102. doi:10.1158/1538-7445.AM2011-1102
Abstract 1104: Insulin-like growth factor-1 is elevated in viscerally obese oesophageal adenocarcinoma patients and expression of its receptor correlates with tumor invasiveness
Authors: Doyle Suzanne L. , Donohoe Claire L. , Lithander Fiona E. , Reynolds John V. , Pidgeon Graham P. , Lysaght Joanne 
Published: June 2012

Abstract
The insulin-like growth factor (IGF) pathway and visceral obesity have been independently linked with esophageal cancer development. This study aimed to delineate the differential and interlinked role of visceral obesity and the IGF-1 system in esophageal adenocarcinoma and squamous cell carcinoma (SCC) progression.
IGF-1 receptor (IGF-1R) mRNA and protein were examined in esophageal SCC (KYSE410, OE21) and adenocarcinoma (OE19, OE33) cell lines by Western Blotting. Tumor cell proliferation in response to IGF-1 was assessed by BrdU incorporation assay. Circulating levels of IGF-1 were measured in 99 serum samples by ELISA and IGF-1R expression was assessed in 50 resected tumor specimens by immunohistochemistry. Results were related to tumor type, gender and visceral adiposity.
Higher IGF-1R mRNA and protein expression were observed in SCC cells, however only adenocarcinoma cell lines showed significantly increased cell proliferation in response to IGF-1 (p&lt;0.01). Significantly higher circulating levels of IGF-1 were detected in patients who had adenocarcinoma (p&lt;0.05) and who were viscerally obese (p&lt;0.05). In resected esophageal adenocarcinoma, IGF-1R expression significantly increased as the tissue progressed along the malignant sequence, with the highest expression observed at the invasive leading edge of the tumor. Uniform IGF-1R expression was observed in SCC tumors.
This novel study is the first of its kind to examine both the differential role of the IGF system in esophageal adenocarcinoma and SCC, and also its association with visceral obesity. These data indicate that in esophageal adenocarcinoma, the IGF-1 axis plays a key role in malignant progression and represents a plausible mechanism by which visceral obesity increases esophageal adenocarcinoma risk.
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 1104. doi:10.1158/1538-7445.AM2011-1104