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Source: Cancer Research
Cancer: Colorectal Cancer
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Total 94 results found since Jan 2013.
Abstract 1663: Selective CDK8 inhibitor SEL120-34A alters expression of interferon-related DNA damage resistance signature genes in colorectal cancer
CDK8 (cyclin-dependent kinase 8) is a kinase component of a multi - protein Mediator complex, involved in transcription control. Several studies indicated that high overexpression and activity of CDK8 could be a driver of malignant progression in colorectal cancer (CRC). Herewith we present molecular insights into mechanism of action of SEL120-34A - a selective small molecule inhibitor of CDK8 kinase. Biochemical and binding studies indicated that SEL120-34A selectively binds and inhibits enzymatic activity of CDK8 in the low nM range. Recently CDK8 has been described as a regulator of STAT1 activity in NK cells where by p...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Rzymski, T., Mikula, M., Szaȷewska–Skuta, M., Zyłkiewicz, E., Sapała, Łukasz, Dolata, I., Kitliłska, A., Goryca, K., Grochowska, A., Cabaȷ, A., Dreas, A., Kucwaȷ, K., Białas, A., Radzimier Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 2958: Discovering therapeutic epigenetic targets using whole genome siRNA screening
Conclusions: A whole genome siRNA screen in combination with the DNMT inhibitor decitabine identified many new target genes that might be epigenetic regulators and potential targets for drug development.Citation Format: Yasuyuki Okamoto, Woonbok Chung, Judith Garriga, Jaroslav Jelinek, Jean-Pierre J. Issa. Discovering therapeutic epigenetic targets using whole genome siRNA screening. [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 2958. doi:10.1158/1538-7445.AM2015-2958
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Okamoto, Y., Chung, W., Garriga, J., Jelinek, J., Issa, J.-P. J. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1180: Hexokinase II plays a pivotal role in colorectal cancer cell proliferation and survival
The Warburg Effect describes the widely observed metabolic phenotype of cancer cells and their heavy reliance on the glycolytic pathway for energy production regardless of oxygen tension. This is a result of alterations to metabolic signaling pathways leading to an upregulation in key glycolytic enzymes. Hexokinase II (HKII) catalyzes the first irreversible step of glycolysis and is often overexpressed in tumors. 3-bromopyruvate (3BP) has been shown to primarily target HKII, and is a promising anti-cancer compound capable of targeting critical metabolic pathways in cancer cells. Here we examine the importance of HKII to ce...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ho, N., Coomber, B. L. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1443: BMP-2 induces motility and invasiveness of colon cancer through upregulation of cancer stem cell
In this study, we investigated the function of BMP-2 and relevance BMP-2 and CSCs in Colon cancer cells.First, We compared the endogenous protein level of parental and spheroid cells by western blotting. The spheroid cells showed higher level of EMT(Epithelial mesenchymal transition) markers N-Cadherin and Snail, CSC markers (EpCAM and CD133), and p Smad1/5 known BMP-2 downstream than the corresponding parental cells. Then expression of EpCAM and CD133 was confirmed by flow cytometry. We found that BMP-2 plays a key role in Cancer stem cell. To determine function of BMP-2 in Colon cancer cells, we stimulated the colon canc...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Kim, B. R., Kim, J. L., Park, S. H., Jeoung, Y. A., Lee, S. I., Min, B.-W., Oh, S. C. Tags: Tumor Biology Source Type: research
Abstract 1215: Small molecule Prodigiosin-mediated p53 pathway restoration and inhibition of self-renewal in colorectal cancer involves c-Jun-mediated {Delta}Np73 inhibition and p73 activation
Tumor suppressor p53 is frequently mutated or inactivated in colorectal cancer while p53 family member p73 is rarely mutated in cancer cells. Small molecules that activate p73 can elicit a p53-like tumor suppressive function and represent a novel approach for p53 pathway restoration. Colorectal tumors contain a small population of cancer stem cells (CSCs) capable of self-renewal that contributes to tumor maintenance and resistance to therapy. Targeting CSCs could improve treatment response and prolong patient survival. We have previously shown that small molecule Prodigiosin restores the p53 pathway via activation of p73 a...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Prabhu, V. V., Zhang, S., Hong, B., Allen, J. E., Lulla, A., Dicker, D. T., El-Deiry, W. S. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1233: Impairment of TFF3 induces cellular apoptosis in prostate cancer cell lines and overexpression of TFF3 may be a prognostic biomarker in human prostate cancers
Background: Human trefoil factor 3(TFF3)/ Intestinal trefoil factor(ITF) is originally known well as an essential regulator for epithelial restitution in gastrointestinal tract and also suggested as a potential cancer marker in serum. Furthermore, the aberrant overexpression of TFF3 has been reported in various human cancers, majorly colorectal cancers, suggesting that TFF3 may play a critical role in tumor growth. However, its molecular signaling pathway remains unclear.Objective: To clarify whether TFF3 is related to survival/anti-apoptotic cell signaling pathways, and to determine that tff3 could be a molecular marker i...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Kim, S.-Y., Liu, J.-Y., Chung, Y.-J. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1246: c-Myc is critical for apoptosis in 4-hyroxynonenal-treated colorectal cancer cells
The transcription factor c-myc has an important role in the control of cell proliferation, differentiation and apoptosis. The dysregulation of c-myc activity is a feature of many cancers. Although it enhances proliferation, the overexpression of c-myc also sensitizes cells to a variety of pro-apoptotic stimuli. 4-hydroxynonenal (HNE) is a reactive lipid that is generated as a consequence of oxidative stress, and is found to be elevated in many solid lesions. HNE is known to promote apoptosis in various cancer cell types, including colorectal cancer cells. We therefore decided to investigate whether c-myc has a role in HNE-...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Wales, C. T., Gristock, R., So, N., Jacobs, A. T. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2043: SATB1 (special AT-rich binding protein 1) as a putative therapeutic target in colorectal cancer
In this study, we have analyzed the function of SATB1 in primary and in established colorectal cancer cell lines and determined the therapeutic relevance of SATB1-specific gene knockdown approaches by RNA interference (RNAi). In CRC cells, an RNAi-mediated knockdown of the SATB1 was achieved by transient or by stable transfection with specific siRNAs or shRNAs-encoding plasmids, each leading to markedly reduced SATB1 mRNA and protein levels. SATB1 knockdown caused an inhibition of proliferation, a deceleration of cell cycle progression and pro-apoptotic effects. Further analyses revealed effects of SATB1 on multiple signal...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Fromberg, A., Rabe, M., Linnebacher, M., Aigner, A. M. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2047: CDK10 promotes tumour growth and chemoresistance in colorectal cancer, and is a potential target for treatment
In this study, we were interested in examining the role of CDK10 in growth, apoptosis, chemoresistance, and as a therapeutic target in CRC.CRC cell lines stably overexpressing CDK10 wild type (WT) as well as a kinase defective/dominant negative (DN) form of CDK10 were established in CRC cell lines RKO, HCT-15 and MIP101. Knockdown of CDK10 was achieved via siRNA. MTS and colony-forming assays were used to examine the response to 5-Fluorouracil (5-FU); TUNEL, caspase 3/7 assays, for apoptosis; and signaling events by immunoblotting. Cell growth in vivo was monitored after injection of cell lines into the flanks of Nude mice...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Weiswald, L.-B., Hasan, M. R., Rahman, M., Pasiliao, C., Tai, I. T. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2577: Aurora kinase inhibitors require PUMA to induce apoptosis and preferentially kill KRAS-mutant colon cancer cells
In this study, we found that inhibition of aurora kinases by siRNA or small-molecule inhibitors led to induction of p53-upregulated modulator of apoptosis (PUMA), a BH3-only BCL-2 family protein, in colorectal cancer cells irrespective of p53 status. Deficiency in PUMA increased polyploidy and abrogated mitochondria-mediated apoptosis induced by aurora kinase inhibitors. In response to aurora kinase inhibition, PUMA was directly activated by p65 through the canonical NF-kB pathway following AKT inhibition. Interestingly, aurora kinase inhibitors were found to preferentially kill KRAS-mutant colon cancer cells, which is ass...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Sun, J., Knickelbein, K., He, K., Chen, D., Yu, J., Zhang, L. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 3088: Inhibition of CDK5 in colorectal cancer
Conclusions: CRC is the second leading cause of cancer related deaths mainly due to the metastatic disease. There are currently no effective pharmacologic treatments for CRC metastases. We have shown that CDK5 is upregulated and overexpressed in metastatic tumors when compared to primary colon tumors. Inhibition of CDK5 either by knockdown or through the use of small molecule inhibitors decreased downstream phosphorylation of specific targets and reduced expression of anti-apoptotic mediators. Together, these data suggest that CDK5 might play a role in metastatic CRC and we’ve identified a potential inhibitor, 20-223 whi...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Robb, C. M. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2337: ADAM17 mediation of cancer stem cell-ness and chemo-resistance in colorectal cancer
INTRODUCTION: Despite the multitude of drug options, most patients with metastatic colorectal cancer (mCRC) die within 3 years of diagnosis. Response to systemic therapy is not durable (
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Wang, R., Fan, F., Boulbes, D., Bhattacharya, R., Ye, X.-C., Xia, L., Ellis, L. Tags: Tumor Biology Source Type: research
Abstract 3373: Identification of inflammation-related genes that regulate tumor-associated stemness using high-throughput siRNA screening
Cancer associated stem cells (CSCs) are considered to be responsible for tumor recurrence, metastasis as well as chemoresistance. These properties of tumor associated stemness are maintained by specialized microenvironment, including inflammation which is a key component of the tumor microenvironment. To study the relationship between inflammation and stemness of CSCs, here, we established a robust high-throughput RNAi screen platform for a global survey of inflammation-related genes affecting CSCs identity via alteration of Oct4 expression. Consequently, we found 72 novel genes from 1027 inflammation-related genes which c...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Xie, J., He, H., Chen, C., Bai, L., Wang, W., Liu, Y., Guo, J., Wu, P., Xiang, R., Luo, Y. Tags: Tumor Biology Source Type: research
Abstract 2640: Small molecule compound NCI-8 induces ERK2-dependent mutant-p53 protein degradation
The tumor suppressor p53 is mutated in over 50% of human cancers leading not only to loss of wild-type p53 function, but also to gain-of-function (GOF) mutant p53 which acts as an oncogene. Mutant p53 is expressed at very high levels and can inhibit residual wild-type p53 activity as well as the function of p53 family member proteins such as p73 or p63. Therefore, targeting mutant p53 by either restoring the p53 pathway or depleting its GOF is an attractive strategy for cancer therapy. NCI-8 is a small molecule compound with dual abilities to induce p53 signal pathway and destabilize mutant p53 protein (deplete GOF) in mut...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Zhang, S., Zhou, L., Dicker, D. T., EL-Deiry, W. S. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 3164: Inflammasomes: fanning the flames of malignant mesothelioma initiation
Malignant mesothelioma (MM) is an aggressive and devastating cancer of the pleural/peritoneal mesothelium related to asbestos exposure. MM has a low survival rate (average: less than 12 months). Despite the causal relationship between asbestos and MM development, the exact mechanism by which asbestos causes MM is still poorly understood. There is an urgent need for the identification of mechanism(s) that may help in early detection and finding new treatment targets for prevention and treatment of MM.We have recently shown that asbestos exposure of human mesothelial cells (HMCs) leads to the activation of the NLRP3 inflamma...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Thompson, J. K., MacPherson, M. B., Beuschel, S. L., Shukla, A. Tags: Immunology Source Type: research
