GAD1 Upregulation Programs Aggressive Features of Cancer Cell Metabolism in the Brain Metastatic Microenvironment
The impact of altered amino acid metabolism on cancer progression is not fully understood. We hypothesized that a metabolic transcriptome shift during metastatic evolution is crucial for brain metastasis. Here, we report a powerful impact in this setting caused by epigenetic upregulation of glutamate decarboxylase 1 (GAD1), a regulator of the GABA neurotransmitter metabolic pathway. In cell-based culture and brain metastasis models, we found that downregulation of the DNA methyltransferase DNMT1 induced by the brain microenvironment–derived clusterin resulted in decreased GAD1 promoter methylation and subsequent upregula...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Patricia M. Schnepp, Dennis D. Lee, Ian H. Guldner, Treasa K. O'Tighearnaigh, Erin N. Howe, Bhavana Palakurthi, Kaitlyn E. Eckert, Tiffany A. Toni, Brandon L. Ashfeld, Siyuan Zhang Tags: Microenvironment and Immunology Source Type: research
SETD1B Activates iNOS Expression in Myeloid-Derived Suppressor Cells
We report here that deficiency in IRF8 results in diminished iNOS expression in both mature CD11b+Gr1− and immature CD11b+Gr1+ myeloid cells in vivo. Strikingly, although IRF8 was silenced in tumor-induced MDSCs, iNOS expression was significantly elevated in tumor-induced MDSCs, suggesting that the expression of iNOS is regulated by an IRF8-independent mechanism under pathologic conditions. Furthermore, tumor-induced MDSCs exhibited diminished STAT1 and NF-κB Rel protein levels, the essential inducers of iNOS in myeloid cells. Instead, tumor-induced MDSCs showed increased SETD1B expression as compared with their cellula...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Priscilla S. Redd, Mohammed L. Ibrahim, John D. Klement, Sarah K. Sharman, Amy V. Paschall, Dafeng Yang, Asha Nayak-Kapoor, Kebin Liu Tags: Microenvironment and Immunology Source Type: research
Variability in Chromatin Architecture and Associated DNA Repair at Genomic Positions Containing Somatic Mutations
Dynamic chromatin structures result in differential chemical reactivity to mutational processes throughout the genome. To identify chromatin features responsible for mutagenesis, we compared chromatin architecture around single-nucleotide variants (SNV), insertion/deletions (indels), and their context-matched, nonmutated positions. We found epigenetic differences between genomic regions containing missense SNVs and those containing frameshift indels across multiple cancer types. Levels of active histone marks were higher around frameshift indels than around missense SNV, whereas repressive histone marks exhibited the rever...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Byungho Lim, Jihyeob Mun, Yong Sung Kim, Seon-Young Kim Tags: Integrated Systems and Technologies Source Type: research
Tissue-Specific Signaling Networks Rewired by Major Somatic Mutations in Human Cancer Revealed by Proteome-Wide Discovery
In this study, we proposed a novel computational oncoproteomics approach, named kinome-wide network module for cancer pharmacogenomics (KNMPx), for identifying actionable mutations that rewired signaling networks and further characterized tumorigenesis and anticancer drug responses. Specifically, we integrated 746,631 missense mutations in 4,997 tumor samples across 16 major cancer types/subtypes from The Cancer Genome Atlas into over 170,000 carefully curated nonredundant phosphorylation sites covering 18,610 proteins. We found 47 mutated proteins (e.g., ERBB2, TP53, and CTNNB1) that had enriched missense mutations at the...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Junfei Zhao, Feixiong Cheng, Zhongming Zhao Tags: Integrated Systems and Technologies Source Type: research
Mathematical Modeling Links Pregnancy-Associated Changes and Breast Cancer Risk
Recent debate has concentrated on the contribution of bad luck to cancer development. The tight correlation between the number of tissue-specific stem cell divisions and cancer risk of the same tissue suggests that bad luck has an important role to play in tumor development, but the full extent of this contribution remains an open question. Improved understanding of the interplay between extrinsic and intrinsic factors at the molecular level is one promising route to identifying the limits on extrinsic control of tumor initiation, which is highly relevant to cancer prevention. Here, we use a simple mathematical model to sh...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Daniel Temko, Yu-Kang Cheng, Kornelia Polyak, Franziska Michor Tags: Integrated Systems and Technologies Source Type: research
BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case–control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G>...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Hermela Shimelis, Romy L.S. Mesman, Catharina Von Nicolai, Asa Ehlen, Lucia Guidugli, Charlotte Martin, Fabienne M.G.R. Calleȷa, Huong Meeks, Emily Hallberg, Jamie Hinton, Jenna Lilyquist, Chunling Hu, Cora M. Aalfs, Kristiina Aittomaki, Irene Andr Tags: Clinical Studies Source Type: research
Widespread Use of Misidentified Cell Line KB (HeLa): Incorrect Attribution and Its Impact Revealed through Mining the Scientific Literature
Continuous cell lines are widely used, but can result in invalid, irreproducible research data. Cell line misidentification is a common problem that can be detected by authentication testing; however, misidentified cell lines continue to be used in publications. Here we explore the impact of one misidentified cell line, KB (HeLa), on the scientific literature. We identified 574 articles between 2000 and 2014 that provided an incorrect attribution for KB, in accordance with its false identity as oral epidermoid carcinoma, but only 57 articles that provided a correct attribution for KB, as HeLa or cervical adenocarcinoma. St...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Liwen Vaughan, Wolfgang Glanzel, Christopher Korch, Amanda Capes–Davis Tags: Perspective Source Type: research
Therapeutic IgE Antibodies: Harnessing a Macrophage-Mediated Immune Surveillance Mechanism against Cancer
IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surveillance and superior effector cell potency against cancer cells. In our recent article, we elaborate our proof-of-concept studies of a mouse/human chimeric IgE antibody (MOv18 IgE), which is specific for the cancer-associated antigen folate receptor alpha. We demonstrate superior antitumor efficacy for IgE co...
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Sophia N. Karagiannis, Debra H. Josephs, Heather J. Bax, James F. Spicer Tags: Reviews Source Type: research
TAM Receptor Tyrosine Kinases in Cancer Drug Resistance
This article reviews the roles of TAMs as tumor drivers and as mediators of chemoresistance, and the potential effectiveness of targeting them as part of therapeutic strategies to delay or combat resistance. Cancer Res; 77(11); 2775–8. ©2017 AACR. (Source: Cancer Research)
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Authors: Mikaella Vouri, Sassan Hafizi Tags: Reviews Source Type: research
Highlights from Recent Cancer Literature
(Source: Cancer Research)
Source: Cancer Research - May 31, 2017 Category: Cancer & Oncology Tags: Breaking Advances Source Type: research
Correction: Metastatic Progression of Prostate Cancer Is Mediated by Autonomous Binding of Galectin-4-O-Glycan to Cancer Cells
(Source: Cancer Research)
Source: Cancer Research - May 14, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research
Correction: Pulsed High-Intensity Focused Ultrasound Enhances Delivery of Doxorubicin in a Preclinical Model of Pancreatic Cancer
(Source: Cancer Research)
Source: Cancer Research - May 14, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research
Correction: Tumor-Intrinsic PD-L1 Signals Regulate Cell Growth, Pathogenesis, and Autophagy in Ovarian Cancer and Melanoma
(Source: Cancer Research)
Source: Cancer Research - May 14, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research
Individualized Breast Cancer Characterization through Single-Cell Analysis of Tumor and Adjacent Normal Cells
There is a need to individualize assays for tumor molecular phenotyping, given variations in the differentiation status of tumor and normal tissues in different patients. To address this, we performed single-cell genomics of breast tumors and adjacent normal cells propagated for a short duration under growth conditions that enable epithelial reprogramming. Cells analyzed were either unselected for a specific subpopulation or phenotypically defined as undifferentiated and highly clonogenic ALDH+/CD49f+/EpCAM+ luminal progenitors, which express both basal cell and luminal cell–enriched genes. We analyzed 420 tumor cells an...
Source: Cancer Research - May 14, 2017 Category: Cancer & Oncology Authors: Manjushree Anjanappa, Angelo Cardoso, Lijun Cheng, Safa Mohamad, Andrea Gunawan, Susan Rice, Yan Dong, Lang Li, George E. Sandusky, Edward F. Srour, Harikrishna Nakshatri Tags: Tumor and Stem Cell Biology Source Type: research
miR-34a and miR-34b/c Suppress Intestinal Tumorigenesis
In conclusion, our results show that miR-34a/b/c suppress tumor formation caused by loss of Apc and control intestinal stem cell and secretory cell homeostasis by downregulation of multiple target mRNAs. Cancer Res; 77(10); 2746–58. ©2017 AACR. (Source: Cancer Research)
Source: Cancer Research - May 14, 2017 Category: Cancer & Oncology Authors: Longchang Jiang, Heiko Hermeking Tags: Tumor and Stem Cell Biology Source Type: research
