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Source: Cancer Research
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Total 26 results found since Jan 2013.
Transcription Factor ZBP-89 Drives a Feedforward Loop of {beta}-Catenin Expression in Colorectal Cancer
In colorectal cancer, APC-mediated induction of unregulated cell growth involves posttranslational mechanisms that prevent proteasomal degradation of proto-oncogene β-catenin (CTNNB1) and its eventual translocation to the nucleus. However, about 10% of colorectal tumors also exhibit increased CTNNB1 mRNA. Here, we show in colorectal cancer that increased expression of ZNF148, the gene coding for transcription factor ZBP-89, correlated with reduced patient survival. Tissue arrays showed that ZBP-89 protein was overexpressed in the early stages of colorectal cancer. Conditional deletion of Zfp148 in a mouse model of Apc-med...
Source: Cancer Research - November 29, 2016 Category: Cancer & Oncology Authors: Bryan E. Essien, Sinȷu Sundaresan, Ramon Ocadiz–Ruiz, Aaron Chavis, Amy C. Tsao, Arthur J. Tessier, Michael M. Hayes, Amanda Photenhauer, Milena Saqui–Salces, Anthony J. Kang, Yatrik M. Shah, Balazs Győrffy, Juanita L. Merchant Tags: Molecular and Cellular Pathobiology Source Type: research
Abstract A18: Epigenetic profiling uncovers the suppressive role of caveolae in Ewing sarcoma
Ewing sarcoma (ES) is the second most common bone tumor in childhood. ES harbors a characteristic gene translocation that gives rise to a fusion protein, most commonly EWS/FLI1 (EF). Caveolin-1 (CAV1) is a direct target of EF, it is overexpressed in ES and has an oncogenic role. CAV1 and the Polymerase I and transcript release factor (PTRF) interact at the plasma membrane and are essential for caveolae formation. The methylome analysis of ES samples and cell lines revealed a hypermethylation in the N-shore islands of the PTRF promoter compared to normal cells. We hypothesize that, as ES cells have very few caveolae and do ...
Source: Cancer Research - April 3, 2016 Category: Cancer & Oncology Authors: Huertas–Martinez, J., Court, F., Rello–Varona, S., Martin, D. H., Almacellas, O., Sainz–Jaspeado, M., Garcia–Monclus, S., Lagares–Tena, L., Buȷ, R., Hontecillas–Prieto, L., Mateo–Lozano, S., Sastre, A., Azo Tags: Epigenetics Source Type: research
C-Raf Colocalizes with DAPK in the Mitochondria
This study identified the interaction of C-Raf with S308 phosphorylated DAPK (pDAPKS308), which together became colocalized in the mitochondria to facilitate mitochondrial remodeling. Combined use of the Raf inhibitors sorafenib and GW5074 had synergistic anticancer effects in vitro and in vivo, but targeted mitochondrial function, rather than the canonical Raf signaling pathway. C-Raf depletion in knockout MEFC-Raf−/− or siRNA knockdown ACHN renal cancer cells abrogated the cytotoxicity of combination therapy. Crystal structure simulation showed that GW5074 bound to C-Raf and induced a C-Raf conformational change that...
Source: Cancer Research - August 31, 2015 Category: Cancer & Oncology Authors: Tsai, Y.-T., Chuang, M.-J., Tang, S.-H., Wu, S.-T., Chen, Y.-C., Sun, G.-H., Hsiao, P.-W., Huang, S.-M., Lee, H.-J., Yu, C.-P., Ho, J.-Y., Lin, H.-K., Chen, M.-R., Lin, C.-C., Chang, S.-Y., Lin, V. C., Yu, D.-S., Cha, T.-L. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
Abstract 4678: A novel nuclear transporter for androgen receptor and AR-variant-7 in castration resistant prostate cancer: Ideal therapeutic target
Conclusions: We identified novel (i) transporter of AR and (ii) approach for treating CRPC in men.Citation Format: Aijaz Parray, Hifzur R. Siddique, Alyssa Langfald, Pooja Singh, Mikihiko Naito, Robert Matusik, Ingo Schmitz, Shahriar Koochekpour, Badrinath R. Konety, Mohammad Saleem. A novel nuclear transporter for androgen receptor and AR-variant-7 in castration resistant prostate cancer: Ideal therapeutic target. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4678. ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Parray, A., Siddique, H. R., Langfald, A., Singh, P., Naito, M., Matusik, R., Schmitz, I., Koochekpour, S., Konety, B. R., Saleem, M. Tags: Endocrinology Source Type: research
Abstract 916: The molecular landscape of colorectal cancer cell lines unveils clinically actionable targets
In conclusion our data suggest that overexpression of TK outliers drives primary resistance to EGFR blockade, and could be used to identify patients unlikely to respond to cetuximab or panitumumab. Moreover, the approach described here can be used to pinpoint colorectal cancers with exquisite dependencies to individual kinases for which clinically approved drugs are already available.Citation Format: Mariangela Russo, Gabriele Picco, Carlotta Cancelliere, Giorgio Corti, Emanuele Valtorta, Silvio Veronese, Marco Beccuti, Francesca Cordero, Federica Di Nicolantonio, Enzo Medico, Alberto Bardelli. The molecular landscape of c...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Russo, M., Picco, G., Cancelliere, C., Corti, G., Valtorta, E., Veronese, S., Beccuti, M., Cordero, F., Di Nicolantonio, F., Medico, E., Bardelli, A. Tags: Prevention Research Source Type: research
Abstract 4956: Hsp27 negatively affects Hippo tumor suppressor pathway to regulate cell survival in cancer
Conclusion: Hsp27 overexpression contributes to inactivation of Hippo pathway. Targeting Hsp27 leads to inactivation of YAP and TAZ onco-proteins affecting cancer cell survival.Impact: Our data further supports the significance of targeting Hsp27 as a treatment option in cancers, especially metastatic malignancies like CRPC.Citation Format: Sepideh Vahid, Daksh Thaper, Amina Zoubeidi. Hsp27 negatively affects Hippo tumor suppressor pathway to regulate cell survival in cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelph...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Vahid, S., Thaper, D., Zoubeidi, A. Tags: Molecular and Cellular Biology Source Type: research
Abstract 4966: Identification of deubiquitinating enzyme USP19 as a regulator of EWS/FLI1 protein turnover in Ewing sarcoma
Ewing sarcoma belongs to the family of pediatric tumors which arise most commonly in bone. The majority of Ewing sarcoma is characterized by a balanced translocation between chromosomes 11 and 22 which encodes for the uniquely expressed fusion protein EWS/FLI1. Tumor cells are crucially dependent on expression of the fusion protein. Protein degradation is an important and highly regulated process in all cells and novel insights are beginning to be applied for cancer therapy. We aim to investigate the mechanism of turnover with the goal to diminish EWS/FLI1 protein and thereby identify novel targets for Ewing sarcoma treatm...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Gierisch, M. E., Lopez-Garcia, L. A., Pfistner, F., Niggli, F. K., Schaefer, B. W. Tags: Molecular and Cellular Biology Source Type: research
Abstract 149: Overexpression of the long non-coding RNA PVT1 and its role in cervical carcinogenesis
Although it is becoming increasingly clear that long non-coding RNAs (lncRNAs) are intricately involved in numerous cancer types, the mechanisms by which they influence carcinogenesis remain poorly understood. The plasmacytoma variant translocation 1 gene (PVT1) is a lncRNA that has been designated as an oncogene due to its contribution to the phenotype of multiple cancers. Further, our lab has recently demonstrated that human papillomavirus (HPV) integration, a hallmark of invasive cervical cancer (ICC), into the PVT1 locus occurs in multiple cervical tumors. The present study was designed to investigate the role of PVT1 ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Iden, M., Fye, S., Ramchandran, R., Rader, J. S. Tags: Molecular and Cellular Biology Source Type: research
Abstract 54: Ezrin enhances signaling and nuclear translocation of the epidermal growth factor receptor in non-small cell lung cancer cells
The cytoskeletal cross linker protein ezrin is a member of the ezrin-radixin-moesin (ERM) family and plays important roles not only in cell motility, cell adhesion, and apoptosis, but also in various cell-signaling pathways. Ezrin interacts with EGFR in the cell membrane and involves in cell motility events, but little is known about the effects of this interaction on the EGFR signaling pathway. We investigated the role of Ezrin in EGFR signaling and nuclear trafficking in non-small cell lung cancer (NSCLC) cell lines. The ligand induced interaction between Ezrin and EGFR was evaluated by immunoprecipitation (IP) and immun...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Saygideger Kont, Y., Celik, H., Erkizan, H. V., Minas, T., Han, J., Toretsky, J., Uren, A. Tags: Molecular and Cellular Biology Source Type: research
Abstract 478: EWS/FLI1 transcription is modulated by the PI3K pathway via SP1 in Ewing sarcoma
Ewing sarcoma (ES) is the second most frequent bone cancer in childhood and it is characterized by the presence of the balanced t(11;22)(q24;q12) translocation in more than 85% of cases, generating a dysregulated transcription factor EWS/FLI1. ES belongs to small-round-blue-cell tumors and it is a very aggressive osteolytic cancer with early tendency for development of metastasis. Mostly it affects bones such as pelvis, femour and ribs but can also arise in soft tissues, mainly in adults. EWS/FLI1 is an essential oncogenic component of ES development which is necessary for tumor cell maintenance, through inappropriate regu...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Giorgi, C., Boro, A., Lopez-Garcia, L. A., Schaefer, B. W., Niggli, F. K. Tags: Tumor Biology Source Type: research
Abstract 479: Inhibition of the splicing of the EWS-FLI1 fusion transcript reverses EWS-FLI1 driven oncogenic expression in Ewing sarcoma
This study has implications for the treatment of ES through inhibition of proteins required for expression of the EWS-FLI1 transcript and identifies a candidate lead compound for further clinical development. Our findings may also open up strategies for treatment of other cancers driven by fusion oncogenes.Citation Format: Patrick J. Grohar, Suntae Kim, Sara Haddock, Guillermo Rangel Rivera, Matt Harlow, Nichole K. Maloney, Konrad Huppi, Kristen Gehlhaus, Magdalena Grandin, Carleen Klumpp-Thomas, Eugen Buehler, Lee J. Helman, Scott E. Martin, Natasha J. Caplen. Inhibition of the splicing of the EWS-FLI1 fusion transcript r...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Grohar, P. J., Kim, S., Haddock, S., Rangel Rivera, G., Harlow, M., Maloney, N. K., Huppi, K., Gehlhaus, K., Grandin, M., Klumpp-Thomas, C., Buehler, E., Helman, L. J., Martin, S. E., Caplen, N. J. Tags: Tumor Biology Source Type: research
Abstract 2030: FRK regulates glioma cell progression by promoting N-cadherin/{beta}-catenin complex formation
In this study, we found that FRK over-expression increased the protein level of N-cadherin, but not that of E-cadherin. Meanwhile, FRK over-expression promoted β-catenin translocation to the plasma membrane, where it formed complex with N-cadherin, while inhibited β-catenin translocation to the nucleus. In addition, down-regulation of N-cadherin by siRNA promoted the migration/ invasion proliferation and inhibited apoptosis of glioma U251 and U87 cells. Interestingly, N-cadherin down-regulation abolished the effect of FRK on glioma cell migration/invasion, proliferation and apoptosis. In summary, these results indicate t...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Shi, Q., Song, X., Yan, H., Wang, J., Zhang, W., Hu, J., Zhou, X., Yu, R. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1393: Correlating the expression of protein kinase C isozymes with the transformed phenotype in colorectal cancer
Protein Kinase C (PKC) is a family of serine/threonine kinases that are involved in almost every signal transduction pathway. Their regulation is mediated by several factors and by binding to a group of scaffolding proteins called RACKs (Adams et al. 2011). The development of PKC modulators with anti-cancer therapeutic value is a major target in cancer. However, this task is made difficult because PKC has an important role to play in normal processes and the PKC family consists of at least 12 different isozymes. In colon cancer, there is differential expression of the PKC isozymes, giving the cancer cells a migratory advan...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Dowling, C. M., Hanly, J., Dalton, T., Kiely, P. A. Tags: Molecular and Cellular Biology Source Type: research
Abstract 718: Systemic delivery of therapeutic siRNA by multifunctional mesoporous silica-based nanocarrier inhibits lung cancer growth and metastasis
In this study, we developed a novel siRNA delivery vector based on our magnetic mesoporous silica nanoparticles (M-MSNs) platform. This nanocarrier was constructed by loading siRNAs into the mesopores of M-MSNs, followed by polyethylenimine (PEI) capping, PEGylation and fusogenic peptide KALA modification. The resultant functionalized delivery system exhibited prolonged half-life in bloodstream, enhanced cell membrane translocation and endosomal escapablity, and favorable tissue biocompatibility and biosafety. Systemic application of vascular endothelial growth factor (VEGF) siRNA via this nanocarrier resulted in remarkabl...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Chen, Y., Gu, H., Xia, W. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 2319: Dynamics of TET methylcytosine dioxygenases in 5-methylcytosine and 5-hydroxymethylcytosine patterning in human cancer cells
This study highlights the multi-dimensional functions of TETs in mediating DNA methylation, hydroxymethylation, and gene expression patterns, and the results reveal that chromatin landscape and DNA sequence composition are regulators of TET function.
Citation Format: Emily L. Putiri, Rochelle L. Tiedemann, Jeong-Hyeon Choi, Keith D. Robertson. Dynamics of TET methylcytosine dioxygenases in 5-methylcytosine and 5-hydroxymethylcytosine patterning in human 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;...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Putiri, E. L., Tiedemann, R. L., Choi, J.-H., Robertson, K. D. Tags: Molecular and Cellular Biology Source Type: research
