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Source: Cancer Research
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Total 807 results found since Jan 2013.
Abstract 4220: Silencing DCLK1 prevents breast cancer cell self-renewal, epithelial mesenchymal transition, circulating tumor cells and metastasis
In this study, we establish the scientific rationale for targeting DCLK1 to inhibit breast cancer proliferation, tumor stem cell growth, self-renewal, EMT, circulating tumor cells (CTCa) and metastasis.Methods: Small interfering RNA (siRNA) against DCLK1 was transfected into breast cancer cell lines (MCF7 and MDAMB231 (triple negative breast cancer cell line)). For analyzing circulating tumor cells MDAMB231 cells are stably transfected with RFP (red fluorescence protein. Cell proliferation, colony formation, mammosphere formation assay (self-renewal), cell migration and invasion assays were assessed to evaluate the effect ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: CHANDRAKESAN, P., Weygant, N., Taylor, V., Berry, W., May, R., Qu, D., Singh, M., Sureban, S., Ali, N., Bronze, M., Houchen, C. Tags: Tumor Biology Source Type: research
Abstract 4240: TORC inhibition enriches for a cancer stem cell-like population with FGFR-dependent Notch1 activation
Conclusions. These data suggest that treatment of TNBC harboring PI3K pathway aberrations with TORC1/2 inhibitors results in decreased tumor growth but may spare a drug-resistant CSC population with FGFR-Notch signaling. Thus, combination of Notch and TORC1/2 inhibitors in addition to chemotherapy may effectively decrease primary tumor growth and prevent recurrences in TNBC patients.Citation Format: Neil E. Bhola, Valerie M. Jansen, Carlos L. Arteaga. TORC inhibition enriches for a cancer stem cell-like population with FGFR-dependent Notch1 activation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Bhola, N. E., Jansen, V. M., Arteaga, C. L. Tags: Tumor Biology Source Type: research
Abstract 4360: Validation of phosphodiesterase 10A as a cancer target
Phosphodiesterase 10A (PDE10) is a cAMP and cGMP degrading PDE isozyme that is highly expressed in the brain striatum where it plays an important role in cognition and psychomotor activity. PDE10 inhibitors are being developed for the treatment of schizophrenia and Huntington's disease and are generally well tolerated, likely because of low expression levels in peripheral tissues. We recently reported high levels of PDE10 in tumors and that genetic silencing by siRNA inhibits tumor cell growth with a high degree of selectivity over normal cells (Li et al., Oncogene 2014). These observations suggest that PDE10 may have an u...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Lee, K., Li, N., Chen, X., Zhu, B., Yet, L., Madeira da Silva, L., Russo, S., Keeton, A. B., Boyd, M. R., Piazza, G. A. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4364: Characterization of mucin-like 1 (MUCL1) in breast cancer and its novel role as a potent activator of cell proliferation
MUCL1 was first identified as a breast-specific gene in 2001. Based on its highly restricted mRNA expression in normal tissues, and its continued expression during breast tumorigenesis and progression (expressed in>90% of breast cancers), MUCL1 is an attractive tumor associated antigen as a potential therapeutic target. However, very little is known about the cellular location and biological functions of the MUCL1 protein, which will have a major impact on its druggability. Here we describe our efforts to fully characterize the cellular localization of MUCL1 and discover its functional roles in breast cancer. Protein seque...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Conley, S. J., Bosco, E., Tice, D., Hollingsworth, R., Herbst, R., Xiao, Z. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4370: GSK3{alpha}/{beta} inhibition as a drug target in prostate cancer
Despite what its namesake suggests, Glycogen Synthase Kinase 3 (GSK3) is a kinase that is implicated in a myriad of signalling pathways and has recently received considerable interest due to its conflicting roles oncogenesis. Though GSK3 has classically been regarded as a tumour suppressor due to in role in supressing WNT signalling, emerging evidence suggests that GSK3 also functions as a tumor promoter by facilitating tumor cell survival and conferring drug resistance in cancer. These tumor promoting effects have been partly linked to the expression of certain NFκB target genes, whose expression in some cancers are infl...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ali, H., Burke, A., O'Connell, E., Sullivan, F., Giles, F., Glynn, S. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4427: Apoptosis, autophagy and ATP: The dynamic interaction of cellular ATP and drug resistance in MET amplified gastric cancer
Conclusions: Overall, our data reveal a novel relationship between low ATP levels and resistance to MET inhibitor-induced cell death. Clinically this is significant because it may discourage the use of combination therapies with autophagy inhibitors in gastric cancer patients whose tumors contain MET amplification.Citation Format: Rebecca Dunbar Schroeder, David Hong, David J. McConkey. Apoptosis, autophagy and ATP: The dynamic interaction of cellular ATP and drug resistance in MET amplified gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Dunbar Schroeder, R., Hong, D., McConkey, D. J. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4440: The functional role of insulin-like growth factor binding protein-2 in esophageal adenocarcinoma chemoresistance
Despite improved understanding of esophageal adenocarcinoma (EAC) progression and advances in endoscopic surveillance and multimodality treatment, patients commonly present with advanced stage disease and demonstrate resistance to therapy, with complete response rates below 40%. Understanding the molecular mechanisms of resistance is crucial for predicting and overcoming this resistance.IGFBP2 is a member of the IGFBP family of proteins that has been shown to modulate both insulin growth factor (IGF) and integrin signaling and is a mediator of cell growth, invasion and resistance in other tumor types. Because these pathway...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Myers, A. L., Lin, L., Nancarrow, D. J., Wang, Z., Ferrer-Torres, D., Beer, D. G., Chang, A. C. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4610: Functional characterization of a multicancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148
Genome wide association studies (GWAS) have mapped multiple independent cancer risk loci (n = 6) to a small region on chr5p15.33 for at least ten distinct cancers, including bladder, breast, glioma, lung, melanoma, non-melanoma skin, ovarian, pancreas, prostate, and testicular germ cell cancer. This region harbors two plausible target genes, TERT which encodes the catalytic subunit of telomerase reverse transcriptase which maintains chromosome ends by adding telomeres repeats, and CLPTM1L which encodes the cleft lip and palate transmembrane protein 1-like protein which promotes cancer cell growth, protect cells from apopto...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Brown, K. M., Fang, J., Jia, J., Wang, Z., Makowski, M., Zhang, T., Hoskins, J., Choi, J., Han, Y., Zhang, M., Xu, M., Kanetsky, P., Thorkell, A., Petersen, G. M., Nathanson, K. L., Amos, C. I., Landi, M. T., Chanock, S. J., Vermeulen, M., Amundadottir, L Tags: Epidemiology 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 4690: Next-generation screen for integrative subtyping and target discovery for KRAS-mutant cancer
Mutations in the small GTPase, KRAS, are found in ∼140,000 new cases of cancer every year in the United States. This heterogeneous class of cancers manifests primarily as adenocarcinomas of the lung, colon and pancreas. These cancers display a wide spectrum of KRAS-dependency and differentially activate downstream effector signaling. The tumors further diverge in their array of co-occurring secondary mutations, expression signatures and KRAS mutant allele. Ultimately, the sole trait these cancers share in common is an obstinate resistance to chemo- and targeted-therapies, making identification of effective treatments an ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Yuan, T. L., Bagni, R., Yi, M., Amzallag, A., Afghani, S., Beam, K., Burgan, W., Fer, N., Garvey, L., Smith, B., Waters, A., Stephens, R., Benes, C., McCormick, F. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4942: Activation of Phosphatase toward the Retinoblastoma protein in breast and colorectal cancer cell spheroids
Excessive phosphorylation of the Retinoblastoma protein is found in most cancer tumor types. Several cyclin dependent kinase (cdk) inhibitors are in development or in clinical trials at the present time. Our previous studies have focused on the regulation of Rb phosphorylation by the phosphatase, PP1. Specificity toward substrates is imparted onto PP1 by many different interacting proteins. In proliferating cells, PP1 is associated with a regulatory protein called PNUTS (Phosphatase Nuclear Targeting Subunit). Our previous experiments have shown that PNUTS inhibits PP1 activity toward specific Rb phosphorylation sites. Fur...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Egger, J., Antonucci, L., Lane, M., Krucher, N. A. Tags: Molecular and Cellular Biology Source Type: research
Abstract 4944: Identification of B-cell lymphoma 6 as a novel therapeutic target in glioblastoma
ConclusionOur data suggest that BCL6 is involved in glioma tumorigenesis through regulating both the TP53 and MEK-ERK pathways, and that BCL6 is a potential therapeutic target for glioma treatment.Citation Format: Ye Chen, Liang Xu, Masaharu Hazawa, Anand M. Thippeswamy, Henry Yang, Markus Müschen, De-Chen Lin, Phillip Koeffler. Identification of B-cell lymphoma 6 as a novel therapeutic target in glioblastoma. [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 4944. doi:...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Chen, Y., Xu, L., Hazawa, M., Thippeswamy, A. M., Yang, H., Muschen, M., Lin, D.–C., Koeffler, P. Tags: Molecular and Cellular Biology Source Type: research
Abstract 4949: HAS2 is a critical effector for AGL mediated regulation of tumor growth
In bladder cancer, reduced levels of Amylo-alpha-1-6-glucosidase-4-alpha-glucanotransferase (AGL), an enzyme involved in glycogenolysis and mutated in glycogen storage disease type III, enhances proliferation in vitro and tumor growth in vivo. To identify how reduced levels of AGL promote bladder cancer growth, we gene expression profiled two bladder cancer cell lines with and without siRNA mediated AGL depletion. This identified that hyaluronic acid synthase 2 (HAS2), an enzyme responsible for hyaluronic acid (HA) synthesis, is upregulated with AGL depletion. We validated this finding in several additional bladder cancer ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Guin, S., Ru, Y., Lew, C. R., Agarwal, N., Owens, C., Theodorescu, D. Tags: Molecular and Cellular Biology Source Type: research
Abstract 5063: Lysyl oxidase-like 2 (LOXL2) from cancer-associated fibroblasts stimulates the progression of gastric carcinoma
Conclusion: LOXL2 from CAF may stimulate the motility of gastric cancer cells. LOXL2 expression in stromal cells may be a useful prognostic factor for patients with gastric cancer.Citation Format: Hiroaki Kasashima, Masakazu Yashiro, Kisyu Kitayama, Go Masuda, Haruhito Kinoshita, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa. Lysyl oxidase-like 2 (LOXL2) from cancer-associated fibroblasts stimulates the progression of gastric carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22;...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Kasashima, H., Yashiro, M., Kitayama, K., Masuda, G., Kinoshita, H., Sakurai, K., Toyokawa, T., Kubo, N., Tanaka, H., Muguruma, K., Ohira, M., Hirakawa, K. Tags: Tumor Biology Source Type: research
Abstract 5109: The CARMA3-Bcl10-MALT1 signalosome mediates NF-{kappa}B activation and cellular invasion in AGTR1-positive breast cancer
Angiotensin II (Ang II) is a potent vasoconstrictor and vascular pro-inflammatory mediator, known classically for its role in promoting arterial dysfunction. Many of these pathogenic effects result from activation of NF-κB in response to stimulation of the type-1 Ang II receptor (AGTR1), a G protein-coupled receptor. We previously discovered that a complex composed of three proteins, CARMA3, Bcl10 and MALT1 (CBM signalosome) mediates AGTR1-dependent activation of NF-κB in vascular cells. Despite its principal role in vascular pathobiology, we recently found that AGTR1 is aberrantly overexpressed in 10-20% of breast cance...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ekambaram, P., Hubel, N., Lee, J.-Y., Klei, L., Concel, V., Delekta, P., Tomlins, S., McAllister-Lucas, L., Lucas, P. Tags: Tumor Biology Source Type: research
