bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5276: Phospholipase A/acyltransferase enzyme activity of H-rev107 inhibits the H-RAS signal pathway
Authors: Tsai Fu-Ming , Wu Chang-Chieh , Wang Chun-Hua , Tsai Tzung-Chieh , Shyu Rong-Yaun , Jiang Shun-Yuan 
Published: May 2015

Abstract
H-rev107, also called HRASLS3 or PLA2G16, is a member of the HREV107 type II tumor suppressor gene family that includes HREV107, Retinoid-inducible gene 1, and HRASLS. The HREV107 protein family contains an NC domain, with unknown function at the N-terminus, and a hydrophobic membrane-anchoring domain at the C-terminus. Previous study showed that the H-rev107 gene specifically expressed in H-ras resistant fibroblasts. However, the mode of action and the site of inhibition of H-rev107 are still unknown. Our results revealed that H-rev107 reduced the levels of activated RAS (RAS-GTP) or Elk1-mediated transactivation in epidermal growth factor stimulated HtTA cells that expressed H-RAS. Further, we found that H-rev107 reduced H-RAS palmitoylation determined by acyl-biotin exchange assay. Palmitoylation or S-acylation is the post-translational attachment of fatty acids to cysteine residues and continuous cycles of de- and reacylation reactions accounts for the specific subcellular distribution of RAS. H-rev107 was shown as a phospholipase A/Acyltransferase (PLA/AT) that involved in the phospholipid metabolism. We next determined whether H-rev107 affected H-RAS palmitoylation through deacylation/acylation by acyl-protein thioesterases (APT1) or PLA/AT using APT1 inhibitor (palmostatin B) or PLA/AT inhibitor (arachidonyl trifluoromethyl ketone, AACOCF3). Treating cells with AACOCF3 can increase H-rev107-induced acylated H-RAS suppression of HtTA cells. Also, AACOCF3 significantly increased the levels of activated RAS and Elk-mediated transactivation in H-rev107 expressed cells. However, treating cells with palmostatin B enhanced H-rev107-induced acylated H-RAS suppression in H-rev107 expressing cells. In conclusion, H-rev107 can inhibit H-RAS palmitoylation to reduce its GTP-form levels and further suppress the downstream signal pathway. Our study suggested that PLA/AT activity of H-rev107 might play an important role in H-rev107 mediated RAS suppression.
Note: This abstract was not presented at the meeting.
Citation Format: Fu-Ming Tsai, Chang-Chieh Wu, Chun-Hua Wang, Tzung-Chieh Tsai, Rong-Yaun Shyu, Shun-Yuan Jiang. Phospholipase A/acyltransferase enzyme activity of H-rev107 inhibits the H-RAS signal 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 5276. doi:10.1158/1538-7445.AM2014-5276
Abstract 5277: Latent transforming growth factor beta-binding protein-3 interacts with midkine
Authors: Weng Chunhua , Dong Haojie , Xu Zhengping 
Published: May 2015

Abstract
Midkine (MK) is a multifunctional heparin-binding growth factor with a molecular weight of 13 kDa, which plays important roles in carcinogenesis. In order to study the action mechanism of MK,we employed a yeast two-hybrid system to screen a human liver cDNA library to determine the putative MK-interacting proteins. cDNA clones containing nucleotide sequences which encode latent transforming growth factor -beta binding protein-3 (LTBP-3) were obtained. The MK/LTBP-3 interaction was confirmed by fluorescence resonance energy transfer analysis. Furthermore, the interaction was analyzed in detail by yeast two-hybrid assay and GST pull down assay. The binding site of MK in LTBP-3 was mapped to the center of the protein, a tandem array of EGF-like repeats, by a fragment deletion analysis in yeast two-hybrid system. The eighth EGF-like domain of LTBP3 plays a critical role in the MK/LTBP-3 interaction in GST pull down assay. On the other hand, four basic amino acids (K-79, R-81, K-86 and K-87) present within the heparin-binding cluster I and II of MK are necessary for the two proteins binding process. These results indicate that MK can bind to LTBP-3, and locate to the eighth EGF-like domain. The heparin-binding clusters of MK are a multifunctional domain, which provide a potential mechanism whereby MK may participate in the TGF-beta system to interfere in carcinogenesis.
Note: This abstract was not presented at the meeting.
Citation Format: Chunhua Weng, Haojie Dong, Zhengping Xu. Latent transforming growth factor beta-binding protein-3 interacts with midkine. [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 5277. doi:10.1158/1538-7445.AM2014-5277
Abstract 5288: PHLPP controls cell polarity by negatively regulating the activity of atypical PKC in colon cancer cells
Authors: Xiong Xiaopeng , li Xin , Gao Tianyan 
Published: May 2015

Abstract
The proper establishment of epithelial polarity allows cells to sense and to respond signals that arise from the microenvironment in a spatiotemporally controlled manner. Increasing evidence has suggested that disruption of polarity promotes the malignant progression of cancer cells. However, the molecular mechanism underlying polarity regulation in the initiation and progression of colon cancer remains largely unknown. PHLPP belongs to a novel family of Ser/Thr protein phosphatases that consists of PHLPP1 and PHLPP2 isoforms. Previously, we have identified conventional PKC isoforms as substrates of PHLPP. Here, we demonstrated that PHLPP controls phosphorylation levels of atypical PKC (aPKC) isoforms, including PKCζ and PKCι, as well. Overexpression of either PHLPP isoform resulted in a decrease in aPKC phosphorylation at both the activation loop (Thr403/410) and the turn motif (Thr555/560) sites in colon cancer cells; conversely, knockdown of PHLPP increased aPKC phosphorylation. In addition, in vitro dephosphorylation experiments revealed that both aPKC isoforms are direct substrates of PHLPP. Since aPKC has been widely implicated in the regulation of cell polarity in intestinal epithelial cells, we determined the function of PHLPP in establishing cell polarity using a 3-D Matrigel culture model. Whereas control Caco2 cells form well polarized cysts in 2 weeks, PHLPP depletion alters the acinar structure by inducing the formation of multiple lumens. Interestingly, knockdown of PKCζ, but not PKCι, results in similar disruption of the polarized lumen structure in Caco2 cells, suggesting that PHLPP may regulate cell polarity through dephosphorylating PKCζ. Taken together, our results identify both aPKC isoforms as novel substrates of PHLPP and downregulation of PHLPP may promote tumorigenesis in colon cancer by disrupting cell polarity.
Citation Format: Xiaopeng Xiong, Xin li, Tianyan Gao. PHLPP controls cell polarity by negatively regulating the activity of atypical PKC in colon cancer cells. [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 5288. doi:10.1158/1538-7445.AM2014-5288
Abstract 5292: The functional role of Tensin4 in hepatocellular carcinoma
Authors: Chan Lo Kong 
Published: May 2015

Abstract
The focal adhesion protein Tensin4 (also known as cten: c-terminal tensin like) is structurally distinct from the three other members in the Tensin family and has been reported to play critical roles in cancer cell migration and invasion in breast and colorectal cancers. However, its expression and potential function in other cancers including hepatocellular carcinoma are not well understood. By quantitative real time PCR and western blotting with Tensin4 specific antibodies, Tensin4 was found to be expressed in a panel of HCC cell lines with a number of cells showing high levels of expression. In these cells, treatment with growth factors (e.g. EGF) significantly induced Tensin4 protein expression; while treatment of pharmacological inhibitors against the kinases in the MAPK signaling cascade abolished this induction. These observations suggested that Tensin4 expression was Ras/MAPK signaling dependent. Intriguingly, the growth factor-induced Tensin4 expression could not be observed in HCC cell lines with low basal Tensin4 expression, implying that other regulatory mechanisms do exist. By immunofluorescence microscopy, the focal adhesion localization of Tensin4 was confirmed in HCC cells. Detail examination of a panel of Tensin4 deletion constructs revealed the requirement of the C-terminal SH2 domain for this specific localization. To examine the functional role of Tensin4, SMMC and BEL7402 HCC cells with high basal expression of Tensin4 were subjected to stable Tensin4 knockdown followed by cell proliferation and cell migration assays. Consistently, we observed that both stable Tensin4 knockdown cells proliferated and migrated in slower rates in vitro. However, the molecular mechanisms regarding this reduction remains to be explored. Taken together, our data suggested that Tensin4 may play a pro-oncogenic role in HCC, possibly function as a downstream effector of Ras/MAPK signaling.
The study was funded by a Hong Kong Research Grants Council GRF grant (775110).
Citation Format: Lo Kong Chan. The functional role of Tensin4 in hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5292. doi:10.1158/1538-7445.AM2014-5292
Abstract 5295: MELK enhances gastric cancer progression via the FAK/paxillin pathway
Authors: Liu Bingya , Du Tao , Qu Ying , Li Jian-fang , Su Liping , Zhu Zheng-gang 
Published: May 2015

Abstract
Elevated MELK expression is a characteristic of multiple tumors and has been correlated with tumorigenesis and tumor development. However, the precise mechanism underlying this correlation is unclear. Here, we report that there are pleiotropic effects associated with enhanced MELK expression in gastric cancer, and this are mediated via the FAK/paxillin pathway. We first show that MELK mRNA and protein expression are both elevated in human gastric cancer, and this is associated with chemoresistance to 5-FU. Knockdown of MELK significantly suppresses cell proliferation, migration, and invasion of gastric cancer both in vitro and in vivo, and decreases the percentages of cells in the G1/G0 phase and increases those in the G2/M and S phases. Moreover, depletion of MELK decreases the amount of actin stress fibers and reduces RhoA activity. Finally, knockdown of MELK decreases the phosphorylation of molecular components of the FAK/Paxillin pathway and prevents gastrin-mediated FAK/paxillin phosphorylation. By contrast, MELK overexpression produces the opposite results, although the differences are moderate. Together, our work suggests that MELK plays an important role in the occurrence and development of gastric cancer, implicates the FAK/Paxillin pathway as the means by which it promotes these effects, and identifies MELK as a potential target for treatment against gastric cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Bingya Liu, Tao Du, Ying Qu, Jian-fang Li, Liping Su, Zheng-gang Zhu. MELK enhances gastric cancer progression via the FAK/paxillin 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 5295. doi:10.1158/1538-7445.AM2014-5295
Abstract 5298: Regulation of urothelial bladder cancer by nicotine and stress neurotransmitters
Authors: John Arokya M. Papu , Banerjee Jheelam , Schuller Hildegard M. 
Published: May 2015

Abstract
Urothelial bladder cancer (UBC) is the 7th most common cancer in men and the 17th most common cancer in women. Smoking is an established risk factor for UBC. However, the mechanisms how smoking induces bladder cancer are poorly understood. Using two established human urothelial bladder cancer cell lines, our data show that nicotine significantly increased the proliferation of both cell lines. Both cell lines produced the stress neurotransmitters norepinephrine and epinephrine and nicotine further enhanced this activity. The broad-spectrum beta-blocker propranolol strongly inhibited base level and nicotine-induced proliferation in both cell lines, identifying beta-adrenergic receptors as mediators. Proliferation in response to exogenous addition of epinephrine, norepinephrine or the selective β-adrenergic agonist isoproterenol and complete blockage of these responses by propranolol support this interpretation. Treatment with the inhibitory neurotransmitter γ-aminobutyric acid (GABA), that inhibits beta-adrenergic receptor-mediated proliferation of other cancer types via inhibition of cAMP formation, was less effective. These findings suggest that urothelial bladder cancer cells are stimulated in their growth via beta-adrenergic receptor signaling independent of cAMP by nicotine or psychological stress. Additional investigations are underway to further dissect the signal transduction pathways involved.
Supported by the State of Tennessee Center of Excellence in Livestock Diseases and Human Health.
Citation Format: Arokya M. Papu John, Jheelam Banerjee, Hildegard M. Schuller. Regulation of urothelial bladder cancer by nicotine and stress neurotransmitters. [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 5298. doi:10.1158/1538-7445.AM2014-5298
Abstract 5301: Rescuing cell polarity with small molecule inhibitors of de-palmitoylation
Authors: Hernandez Jeannie L. , Davda Dahvid , Majmudar Jaimeen , Labby Kristin J. , Gang Margery , Pasupuleti Sirisha , Seita Makoto , Martin Brent R. 
Published: May 2015

Abstract
Protein palmitoylation is a unique post-translational modification required for the membrane anchoring and trafficking of numerous regulatory proteins that play key roles in cell growth, polarity, and signaling. Using a pulse-chase palmitoylation proteomics approach, we identified the tumor suppressor Scrib as the most dynamic, enzymatically regulated palmitoylated protein in malignant cells. Scrib localizes at the basolateral membrane where it regulates epithelial cell apical-basolateral polarity, junctional integrity, proliferation, and metastasis. Loss of Scrib at the plasma membrane cooperates with oncogenic Ras or Myc overexpression to drive tumor formation, promote epidermal to mesenchymal transition (EMT), and bypass contact inhibition. Interestingly, overexpression of Snail in polarized cells eliminates Scrib membrane localization. We recently reported a class of in vivo active small selective inhibitors of the acyl protein thioesterases APT1 and APT2. Addition of a small molecule APT2 inhibitor restores Scrib membrane localization and enhances E-Cadherin expression, overcoming Snail-mediated repression of E-cad. These findings suggest that thioesterases, predominantly APT2 more than APT1, regulate the palmitoylation of cell polarity proteins, and highlight a strategy to attenuate oncogenic signaling and restore cell polarity pathways in malignant cells.
Citation Format: Jeannie L. Hernandez, Dahvid Davda, Jaimeen Majmudar, Kristin J. Labby, Margery Gang, Sirisha Pasupuleti, Makoto Seita, Brent R. Martin. Rescuing cell polarity with small molecule inhibitors of de-palmitoylation. [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 5301. doi:10.1158/1538-7445.AM2014-5301
Abstract 5302: CITED2 as a molecular switch for hypoxia-mediated proliferation
Authors: Wang Yuan-Hung , Kuo Ming-Han , Huang Chien-Fu , Hsiao Shih-Hsin , Wu Cheng-Wen , Chou Yu-Ting 
Published: May 2015

Abstract
Hypoxia, the reduction of oxygen levels in cells or tissues, elicits a set of genes to adjust physiological and pathological demands during normal development and cancer progression. Hypoxia-mediated stabilization of hypoxia-inducible factor (HIF) 1α and 2α contributes to transcriptional regulation of genes involved in hypoxia-mediated physiological adaptation. Till now, the molecular mechanism of how HIF1α and HIF2α signaling regulates cancer cell proliferation and quiescence in hypoxic microenvironment is little understood. Here, we reported that CITED2, a cytokine inducible transcriptional modulator, is induced by HIF2α to regulate cell proliferation and quiescence. We observed that HIF2α expression is induced by hypoxia in a subgroup of lung cancer cells, proliferation of which is regulated via HIF2α/CITED2 signaling. Interestingly, HIF1α-silencing promotes hypoxic-mediated cell proliferation in the HIF2α-positive lung cancer cells. In contrast, knockdown of HIF2α as well as CITED2 attenuates cell growth, suggesting that HIF2α/CITED2 signaling functions as a molecular switch for cell proliferation and quiescence. Soft-agar assay showed that HIF2α promotes anchorage-independent growth of cancer cells, which can be inhibited by CITED2-silencing. We observed that upon hypoxia induction, CITED2 enhances MYC-mediated transactivation of downstream target genes. Our findings provide a novel oncogenic role of CITED2 in hypoxia with potential as a biomarker and therapeutic targets for lung cancer.
Citation Format: Yuan-Hung Wang, Ming-Han Kuo, Chien-Fu Huang, Shih-Hsin Hsiao, Cheng-Wen Wu, Yu-Ting Chou. CITED2 as a molecular switch for hypoxia-mediated proliferation. [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 5302. doi:10.1158/1538-7445.AM2014-5302
Abstract 5308: A proteome analysis of the cadmium response in human bronchial epithelial cells: Identification of potential biomarkers related to cadmium exposure
Authors: Lau Andy T. Y. , Chen De-Ju , Du Ji-Ying , Xu Yan-Ming 
Published: May 2015

Abstract
Cadmium (Cd) and Cd derivatives are ubiquitously-distributed in the living environment. In particular, the contamination of Cd in the food chain, occupational exposure and tobacco smoke provide important sources of human exposure to Cd. Here, we provide a proteomic analysis of human bronchial epithelial cells (BEAS-2B) treated with CdCl2, with the aim of identifying protein response to Cd toxicity. Comparative proteome analysis was conducted at the intracellular (cell lysate) and extracellular (spent medium) levels to identify global changes in the protein expression profiles of sham-exposed and Cd-treated cells. Proteins were separated by two-dimensional electrophoresis and visualized by silver staining. We reported that while a low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity and produced no significant proteome changes between the treated group and the control, however, high levels (20 or 30 μM) of Cd treatment for 36 h induced obvious proteome changes and cell death in BEAS-2B cells. Differentially-expressed proteins were identified by LC-MS/MS and further confirmed by Western blot analysis. The proteins that were significantly up-regulated included molecular chaperones (e.g. HSP90B1, HSPA6, TCP-1-epsilon), antioxidative stress enzymes (e.g. GST-P1 and -O1, thioredoxin, peroxiredoxin-1 and -2), as well as pro-apoptotic proteins (e.g. GAPDH, eIF-5A-1). Interestingly, we also found that the redox-sensitive transcription factor NF-κB is up-regulated; while the tumor suppressor p53 is significantly down-regulated by high levels of Cd treatment. Pretreatment with the thiol antioxidant glutathione before Cd treatment effectively abrogated the up-regulation or down-regulation of these marker proteins and prevented cell death. Taken together, our results demonstrate that high levels of Cd cause oxidative stress-induced cytotoxicity, while a low level of Cd may exert a more noticeable effect after long-term exposure, but not after transient exposure.
Citation Format: Andy T. Y. Lau, De-Ju Chen, Ji-Ying Du, Yan-Ming Xu. A proteome analysis of the cadmium response in human bronchial epithelial cells: Identification of potential biomarkers related to cadmium exposure. [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 5308. doi:10.1158/1538-7445.AM2014-5308
Abstract 5317: Photonic crystal microarray sensing of breast cancer cell line lysates
Authors: Chakravarty Swapnajit , Tang Naimei , Yan Hai , Yang Chun-ju , Zou Yi , Shen Qiang , Chen Ray 
Published: May 2015

Abstract
Monitoring of protein expression changes in cells or in real tissue is commonly based on western blot and protein microarray. However, these assays have limitations that include lack of detection sensitivity and accuracy. Furthermore, fluorescent, radioactive or magnetic tags or labels are typically needed for signal transduction, which may not always be preferable, as more and more new markers are being discovered. In this study, we have used our silicon chip based label free high throughput high sensitivity XtremeSens Diagnostics benchtop nanophotonic platform to detect the target proteins that are regulated by TAM67. The platform has currently demonstrated the smallest sensor on chip with the highest sensitivity down to 67femtograms per milliliter with specificity. The target proteins were selected based on western blot results which shows that when Tam67 is overexpressed in MCF-7 Tam67 clone cells, PCNA is up-regulated; ß-catenin, cyclinD1, p-EGFR expression are down-regulated, and E-cadherin seems to have no change. The probe antibodies were printed on unique photonic crystal microcavities and cell lysates were detected by a label-free method.
The assay is based on the highly sensitive photonic crystal platform in silicon-on-insulator chips in which light-matter interaction is enhanced due to confinement and guiding of light on length scales of the wavelength of light. The probe proteins are immobilized on unique photonic crystal microcavities in the array. All sensors are exposed to the analyte at the same instant of time. The binding interaction alters the refractive index of the resonance cavity and this is detected as a shift in the resonance wavelength trapped by the device. The resonance shift is detected directly and does not require any secondary labeling. Specificity is demonstrated using a sandwich assay in which a second antibody was introduced following the initial binding and washing steps and a secondary resonance wavelength shift is observed.
The impact of this study will provide the wide range of applications including the study of cancer biomarker, signal transfection pathway, clinical diagnosis of diseases, commercialization potential is envisioned in other civilian markets such as environmental pollution sensing, food pathogen detection and biodefense.
Citation Format: Swapnajit Chakravarty, Naimei Tang, Hai Yan, Chun-ju Yang, Yi Zou, Qiang Shen, Ray Chen. Photonic crystal microarray sensing of breast cancer cell line lysates. [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 5317. doi:10.1158/1538-7445.AM2014-5317