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Total 665 results found since Jan 2013.

Increased TGFα as a mechanism of acquired resistance to the anti-EGFR inhibitor cetuximab through EGFR-MET interaction and activation of MET signaling in colon cancer cells.
CONCLUSIONS: These results suggest that overexpression of TGFα through induction of EGFR-MET interaction contributes to cetuximab resistance in CRC cells. PMID: 24122793 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - October 11, 2013 Category: Cancer & Oncology Authors: Troiani T, Martinelli E, Napolitano S, Vitagliano D, Ciuffreda LP, Costantino S, Morgillo F, Capasso A, Sforza V, Nappi A, De Palma R, D'aiuto E, Berrino L, Bianco R, Ciardiello F Tags: Clin Cancer Res Source Type: research

A High-Throughput-Compatible 3D Microtissue Co-Culture System for Phenotypic RNAi Screening Applications
Cancer cells in vivo are coordinately influenced by an interactive 3D microenvironment. However, identification of drug targets and initial target validations are usually performed in 2D cell culture systems. The opportunity to design 3D co-culture models that reflect, at least in part, these heterotypic interactions, when coupled with RNA interference, would enable investigations on the phenotypic impact of gene function in a model that more closely resembles tumor growth in vivo. Here we describe a high-throughput–compatible method to discover cancer gene functions in a co-culture 3D tumor microtissue model system ...
Source: Journal of Biomolecular Screening - November 12, 2013 Category: Molecular Biology Authors: Thoma, C. R., Stroebel, S., Rosch, N., Calpe, B., Krek, W., Kelm, J. M. Tags: Technical Note Source Type: research

Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXR{gamma} activation
Tumor metastasis and lack of NKG2D ligand (NKG2DL) expression are associated with poor prognosis in patients with colon cancer. Here, we found that spironolactone (SPIR), an FDA-approved diuretic drug with a long-term safety profile, can up-regulate NKG2DL expression in multiple colon cancer cell lines by activating the ATM–Chk2-mediated checkpoint pathway, which in turn enhances tumor elimination by natural killer cells. SPIR can also up-regulate the expression of metastasis-suppressor genes TIMP2 and TIMP3, thereby reducing tumor cell invasiveness. Although SPIR is an aldosterone antagonist, its antitumor effects a...
Source: The Journal of Experimental Medicine - November 18, 2013 Category: Internal Medicine Authors: Leung, W.-H., Vong, Q. P., Lin, W., Janke, L., Chen, T., Leung, W. Tags: Articles Source Type: research

Pyrido2,3-dpyrimidines: Discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors.
Abstract DYRK1B is a kinase over-expressed in certain cancer cells (including colon, ovarian, pancreatic, etc.). Recent publications have demonstrated inhibition of DYRK1B could be an attractive target for cancer therapy. From a data-mining effort, the team has discovered analogues of pyrido[2,3-d]pyrimidines as potent enantio-selective inhibitors of DYRK1B. Cells treated with a tool compound from this series showed the same cellular effects as down regulation of DYRK1B with siRNA. Such effects are consistent with the proposed mechanism of action. Progress of the SAR study is presented. PMID: 24239188 [PubMed...
Source: Bioorganic and Medicinal Chemistry Letters - November 1, 2013 Category: Chemistry Authors: Anderson K, Chen Y, Chen Z, Dominique R, Glenn K, He Y, Janson C, Luk KC, Lukacs C, Polonskaia A, Qiao Q, Railkar A, Rossman P, Sun H, Xiang Q, Vilenchik M, Wovkulich P, Zhang X Tags: Bioorg Med Chem Lett Source Type: research

{beta}1Pix Interacts Directly with {beta}-Catenin Cell Biology
We report the novel observations that β1Pix binds directly to β-catenin, an action requiring both the β1Pix DH and dimerization domains but not β1Pix GEF activity. In human colon cancer cells, activation of β-catenin signaling with LiCl decreased β1Pix/β-catenin association in the cytosol and increased nuclear binding of β-catenin to β1Pix. Nuclear association of β1Pix and β-catenin was independent of Rac1 expression and activation; down- and up-regulating Rac1 expression levels did not alter nuclear β1Pix/β-catenin association. Ectopic β1Pix expression enhanced LiCl-induced β-catenin transcriptional activit...
Source: Journal of Biological Chemistry - November 22, 2013 Category: Chemistry Authors: Chahdi, A., Raufman, J.-P. Tags: Signal Transduction Source Type: research

Combined incubation of colon carcinoma cells with phorbol ester and mitochondrial uncoupling agents results in synergic elevated reactive oxygen species levels and increased γ-glutamyltransferase expression.
Abstract The NADPH oxidase (NOX) is a significant determinant for the expression and activity of γ-glutamyltransferase (GGT), which is frequently upregulated after increased levels of reactive oxygen species (ROS) and oxidative stress. Earlier studies on human colon carcinoma HT-29 cells have shown that treatment with phorbol 12-myristate 13-acetate (PMA) activates NOX thus increasing the intracellular level of ROS and upregulating GGT. Another important source of cellular ROS is the mitochondria, and treatment with the mitochondria uncoupler carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP) results in ...
Source: Molecular and Cellular Biochemistry - November 27, 2013 Category: Biochemistry Authors: Pandur S, Ravuri C, Moens U, Huseby NE Tags: Mol Cell Biochem Source Type: research

Comprehensive analysis of beta-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/beta-catenin signaling
Conclusions: Based on the large number of potential beta-catenin target genes found to be similarly regulated in DLD1, SW480 and LS174T cells as well as the large overlap with confirmed beta-catenin target genes, we conclude that DLD1 and SW480 colon carcinoma cell lines are suitable model systems to study Wnt/beta-catenin signaling and associated colorectal carcinogenesis. Furthermore, the confirmed and the newly identified potential beta-catenin target genes are useful starting points for further studies.
Source: BMC Genomics - Latest articles - January 28, 2014 Category: Genetics & Stem Cells Authors: Andreas HerbstVindi JurinovicStefan KrebsSusanne ThiemeHelmut BlumBurkhard GökeFrank Kolligs Source Type: research

Ezrin expression and cell survival regulation in colorectal cancer.
We report for the first time that p-ezrin T567 is downstream of the IGF1R signaling and demonstrate that ezrin regulates cell survival through survivin/XIAP modulation. PMID: 24462708 [PubMed - as supplied by publisher]
Source: Cellular Signalling - January 22, 2014 Category: Cytology Authors: Leiphrakpam PD, Rajput A, Mathiesen M, Agarwal E, Lazenby AJ, Are C, Brattain MG, Chowdhury S Tags: Cell Signal Source Type: research

End-binding protein 1 (EB1) up-regulation is an early event in colorectal carcinogenesis
Highlights: Abstract: End-binding protein (EB1) is a microtubule protein that binds to the tumor suppressor adenomatous polyposis coli (APC). While EB1 is implicated as a potential oncogene, its role in cancer progression is unknown. Therefore, we analyzed EB1/APC expression at the earliest stages of colorectal carcinogenesis and in the uninvolved mucosa (“field effect”) of human and animal tissue. We also performed siRNA-knockdown in colon cancer cell lines. EB1 is up-regulated in early and field carcinogenesis in the colon, and the cellular/nano-architectural effect of EB1 knockdown depended on the genetic context. T...
Source: FEBS Letters - February 3, 2014 Category: Biochemistry Authors: Yolanda Stypula-Cyrus, Nikhil N. Mutyal, Mart Dela Cruz, Dhananjay P. Kunte, Andrew J. Radosevich, Ramesh Wali, Hemant K. Roy, Vadim Backman Tags: Research Letters Source Type: research

Quercetin regulates the sestrin 2-AMPK-p38 MAPK signaling pathway and induces apoptosis by increasing the generation of intracellular ROS in a p53-independent manner.
Abstract The induction of apoptosis in cancer cells is a therapeutic strategy for the treatment of cancer. In the present study, we investigated the regulatory mechanisms responsible for quercetin-induced apoptosis, mamely the increased expression of sestrin 2 and the activation of the 5' AMP-activated protein kinase (AMPK)/p38 MAPK signaling pathway. Our results revealed that quercetin induced apoptosis by generating the production of intracellular reactive oxygen species (ROS) and increasing the expression of sestrin 2. The induction of apoptosis by quercetin occurred through the activation of the AMPK/p38 s...
Source: International Journal of Molecular Medicine - February 20, 2014 Category: Molecular Biology Authors: Kim GT, Lee SH, Kim JI, Kim YM Tags: Int J Mol Med Source Type: research

Oxaliplatin activates the KEAP1/NRF2 antioxidant system conferring protection against the cytotoxicity of anticancer drugs.
Abstract Oxaliplatin is an important drug in the treatment of advanced metastatic colorectal cancer. NF-E2 P45-related factor 2 (NRF2) is a key transcription factor that controls genes encoding cytoprotective and detoxifying enzymes through antioxidant response elements (AREs) in their regulatory regions. Here, we report that oxaliplatin is an activator of the NRF2 signaling pathway, with up-regulation of ARE-driven genes and glutathione elevation. An injection of oxaliplatin into mice enhanced the expression of glutathione transferases and antioxidant enzymes in the small and large intestines of wild-type (WT) mi...
Source: Free Radical Biology and Medicine - February 17, 2014 Category: Biology Authors: Wang XJ, Li Y, Luo L, Wang H, Chi Z, Xin A, Li X, Wu J, Tang X Tags: Free Radic Biol Med Source Type: research

Hypoxia differentially regulated CXCR4 and CXCR7 signaling in colon cancer
Background: HIF-1alpha and CXCR4/CXCL12 have crucial roles in the metastatic process of colorectal cancer. Our aim was to study the significance of targeting HIF-1alpha and the CXCR4/CXCL12 axis in colorectal cancer to prevent the dissemination process in vitro. Methods: We investigated CXCR4 and CXCR7 mRNA and protein expression in human colon carcinomas and the modulation of their expression by hypoxia and HIF-1alpha in colon cancer cell lines. The migration of tumor cells in a Boyden chamber was studied after CXCR4 inhibition with siRNA or the CXCR4/CXCL12 neutraligand, chalcone 4. Results: Analysis of a cohort of colon...
Source: Molecular Cancer - March 14, 2014 Category: Cancer & Oncology Authors: Benoît RomainMuriel Hachet-HaasSerge RohrCécile BrigandJean-Luc GalziMarie-Pierre GaubErwan PencreachDominique Guenot Source Type: research

EIF5A2 is a novel chemoresistance gene in breast cancer.
CONCLUSION: This study shows that eIF-5A2 plays an important role in doxorubicin chemoresistance in breast cancer cells. PMID: 24638963 [PubMed - as supplied by publisher]
Source: Breast Cancer - March 18, 2014 Category: Cancer & Oncology Authors: Liu Y, Du F, Chen W, Yao M, Lv K, Fu P Tags: Breast Cancer Source Type: research

Sodium Butyrate Induces Apoptosis of Human Colon Cancer Cells by Modulating ERK and Sphingosine Kinase 2.
CONCLUSION: ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT. PMID: 24709100 [PubMed - in process]
Source: Biomedical and Environmental Sciences : BES - March 1, 2014 Category: Biomedical Science Authors: Xiao M, Liu YG, Zou MC, Zou F Tags: Biomed Environ Sci Source Type: research

Sa1959 Curcumin Induces Autophagic Survival of DCLK1+VE Colon Cancer Stem Cells (CSCs), While Co-Treatment With Curcumin and DCLK1-siRNA Eliminates CSCS: Role of Long and Short Isofoms of DCLK1
Source: Gastroenterology - May 1, 2014 Category: Gastroenterology Authors: Malaney R. O'Connell, Shubhashish Sarkar, Carla Kantara, Pomila Singh Source Type: research