Models in Translational Oncology: A Public Resource Database for Preclinical Cancer Research
The devastating diseases of human cancer are mimicked in basic and translational cancer research by a steadily increasing number of tumor models, a situation requiring a platform with standardized reports to share model data. Models in Translational Oncology (MiTO) database was developed as a unique Web platform aiming for a comprehensive overview of preclinical models covering genetically engineered organisms, models of transplantation, chemical/physical induction, or spontaneous development, reviewed here. MiTO serves data entry for metastasis profiles and interventions. Moreover, cell lines and animal lines including to...
Source: Cancer Research - May 14, 2017 Category: Cancer & Oncology Authors: Claudia Galuschka, Rumyana Proynova, Benȷamin Roth, Hellmut G. Augustin, Karin Muller–Decker Tags: Reviews Source Type: research
Highlights from Recent Cancer Literature
(Source: Cancer Research)
Source: Cancer Research - May 14, 2017 Category: Cancer & Oncology Tags: Breaking Advances Source Type: research
Correction: UTX and MLL4 Coordinately Regulate Transcriptional Programs for Cell Proliferation and Invasiveness in Breast Cancer Cells
(Source: Cancer Research)
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research
Correction: Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy
(Source: Cancer Research)
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research
Role of CBX4 in the Colorectal Carcinoma Metastasis—Response
(Source: Cancer Research)
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Xin Wang, Tiebang Kang Tags: Letters to the Editor Source Type: research
Role of CBX4 in the Colorectal Carcinoma Metastasis—Letter
(Source: Cancer Research)
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Valentina Sancisi, Alessia Ciarrocchi Tags: Letters to the Editor Source Type: research
WNT/{beta}-Catenin Directs Self-Renewal Symmetric Cell Division of hTERThigh Prostate Cancer Stem Cells
Cancer stem-like cells (CSC) drive cancer progression and recurrence. Self-renewal expansion of CSC is achieved through symmetric cell division, yet how external stimuli affect intracellular regulatory programs of CSC division modes and stemness remains obscure. Here, we report that the hTERThigh prostate cancer cells exhibit CSC properties, including a stem cell–associated gene expression signature, long-term tumor-propagating capacity and epithelial-to-mesenchymal transition. In promoting the self-renewal symmetric division of hTERThigh prostate cancer cells, WNT3a dramatically decreased the ratio of hTERThigh prostate...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Kai Zhang, Yanjing Guo, Xue Wang, Huifang Zhao, Zhongzhong Ji, Chaping Cheng, Li Li, Yuxiang Fang, Dawei Xu, Helen He Zhu, Wei-Qiang Gao Tags: Tumor and Stem Cell Biology Source Type: research
The Histone Methyltransferase DOT1L Promotes Neuroblastoma by Regulating Gene Transcription
Myc oncoproteins exert tumorigenic effects by regulating expression of target oncogenes. Histone H3 lysine 79 (H3K79) methylation at Myc-responsive elements of target gene promoters is a strict prerequisite for Myc-induced transcriptional activation, and DOT1L is the only known histone methyltransferase that catalyzes H3K79 methylation. Here, we show that N-Myc upregulates DOT1L mRNA and protein expression by binding to the DOT1L gene promoter. shRNA-mediated depletion of DOT1L reduced mRNA and protein expression of N-Myc target genes ODC1 and E2F2. DOT1L bound to the Myc Box II domain of N-Myc protein, and knockdown of DO...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Matthew Wong, Andrew E.L. Tee, Giorgio Milazzo, Jessica L. Bell, Rebecca C. Poulos, Bernard Atmadibrata, Yuting Sun, Duohui Jing, Nicholas Ho, Dora Ling, Pei Yan Liu, Xu Dong Zhang, Stefan Huttelmaier, Jason W.H. Wong, Jenny Wang, Patsie Polly, Giovanni P Tags: Tumor and Stem Cell Biology Source Type: research
Mcl-1 Degradation Is Required for Targeted Therapeutics to Eradicate Colon Cancer Cells
In this study, we present evidence that Mcl-1 participates directly in determining effective therapeutic responses in colon cancer cells. In this setting, Mcl-1 degradation was induced by a variety of multikinase inhibitor drugs, where it relied upon GSK3β phosphorylation and FBW7-dependent ubiquitination. Specific blockade by genetic knock-in (KI) abolished apoptotic responses and conferred resistance to kinase inhibitors. Mcl-1-KI also suppressed the antiangiogenic and anti-hypoxic effects of kinase inhibitors in the tumor microenvironment. Interestingly, these same inhibitors also induced the BH3-only Bcl-2 family prot...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Jingshan Tong, Peng Wang, Shuai Tan, Dongshi Chen, Zaneta Nikolovska-Coleska, Fangdong Zou, Jian Yu, Lin Zhang Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
Energy Balance Modulation Impacts Epigenetic Reprogramming, ER{alpha} and ER{beta} Expression, and Mammary Tumor Development in MMTV-neu Transgenic Mice
The association between obesity and breast cancer risk and prognosis is well established in estrogen receptor (ER)-positive disease but less clear in HER2-positive disease. Here, we report preclinical evidence suggesting weight maintenance through calorie restriction (CR) may limit risk of HER2-positive breast cancer. In female MMTV-HER2/neu transgenic mice, we found that ERα and ERβ expression, mammary tumorigenesis, and survival are energy balance dependent in association with epigenetic reprogramming. Mice were randomized to receive a CR, overweight-inducing, or diet-induced obesity regimen (n = 27/group). Subsets of ...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Emily L. Rossi, Sarah M. Dunlap, Laura W. Bowers, Subreen A. Khatib, Steven S. Doerstling, Laura A. Smith, Nikki A. Ford, Darcy Holley, Powel H. Brown, Marcos R. Estecio, Donna F. Kusewitt, Linda A. deGraffenried, Scott J. Bultman, Stephen D. Hursting Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
Kinome-Wide RNA Interference Screen Reveals a Role for PDK1 in Acquired Resistance to CDK4/6 Inhibition in ER-Positive Breast Cancer
In this study, we used a kinome-wide siRNA screen to identify kinases that, when downregulated, yield sensitivity to the CDK4/6 inhibitor ribociclib. In this manner, we identified 3-phosphoinositide-dependent protein kinase 1 (PDK1) as a key modifier of ribociclib sensitivity in estrogen receptor–positive MCF-7 breast cancer cells. Pharmacologic inhibition of PDK1 with GSK2334470 in combination with ribociclib or palbociclib, another CDK4/6 inhibitor, synergistically inhibited proliferation and increased apoptosis in a panel of ER-positive breast cancer cell lines. Ribociclib-resistant breast cancer cells selected by chr...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Valerie M. Jansen, Neil E. Bhola, Joshua A. Bauer, Luigi Formisano, Kyung–Min Lee, Katherine E. Hutchinson, Agnieszka K. Witkiewicz, Preston D. Moore, Monica Valeria Estrada, Violeta Sanchez, Paula G. Ericsson, Melinda E. Sanders, Paula R. Pohlmann, Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
Targeted Degradation of BET Proteins in Triple-Negative Breast Cancer
In this study, we report the development of a second-generation BET protein degrader, BETd-246, which exhibits superior selectivity, potency, and antitumor activity. In human TNBC cells, BETd-246 induced degradation of BET proteins at low nanomolar concentrations within 1 hour of exposure, resulting in robust growth inhibition and apoptosis. BETd-246 was more potent and effective in TNBC cells than its parental BET inhibitor compound BETi-211. RNA-seq analysis revealed predominant downregulation of a large number of genes involved in proliferation and apoptosis in cells treated with BETd-246, as compared with BETi-211 trea...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Longchuan Bai, Bing Zhou, Chao-Yie Yang, Jiao Ji, Donna McEachern, Sally Przybranowski, Hui Jiang, Jiantao Hu, Fuming Xu, Yujun Zhao, Liu Liu, Ester Fernandez-Salas, Jing Xu, Yali Dou, Bo Wen, Duxin Sun, Jennifer Meagher, Jeanne Stuckey, Daniel F. Hayes, Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
High-Throughput Genomic Profiling of Adult Solid Tumors Reveals Novel Insights into Cancer Pathogenesis
Genomic profiling is widely predicted to become a standard of care in clinical oncology, but more effective data sharing to accelerate progress in precision medicine will be required. Here, we describe cancer-associated genomic profiles from 18,004 unique adult cancers. The dataset was composed of 162 tumor subtypes including multiple rare and uncommon tumors. Comparison of alteration frequencies to The Cancer Genome Atlas identified some differences and suggested an enrichment of treatment-refractory samples in breast and lung cancer cohorts. To illustrate novelty within the dataset, we surveyed the genomic landscape of r...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Ryan J. Hartmaier, Lee A. Albacker, Juliann Chmielecki, Mark Bailey, Jie He, Michael E. Goldberg, Shakti Ramkissoon, James Suh, Julia A. Elvin, Samuel Chiacchia, Garrett M. Frampton, Jeffrey S. Ross, Vincent Miller, Philip J. Stephens, Doron Lipson Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
NR1D1 Recruitment to Sites of DNA Damage Inhibits Repair and Is Associated with Chemosensitivity of Breast Cancer
In this study, we identified a novel function of nuclear receptor NR1D1 in DNA repair, which enhanced chemosensitivity in breast cancer cells. NR1D1 inhibited both nonhomologous end joining and homologous recombination double-strand breaks repair, and delayed the clearance of γH2AX DNA repair foci that formed after treatment of doxorubicin. PARylation of NR1D1 by PARP1 drove its recruitment to damaged DNA lesions. Deletion of the ligand binding domain of NR1D1 that interacted with PARP1, or treatment of 6-(5H)-phenanthridinone, an inhibitor of PARP1, suppressed the recruitment of NR1D1 to DNA damaged sites, indicating PAR...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Na-Lee Ka, Tae-Young Na, Hyelin Na, Min-Ho Lee, Han-Su Park, Sewon Hwang, Il Yong Kim, Je Kyung Seong, Mi-Ock Lee Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
Sigma1 Targeting to Suppress Aberrant Androgen Receptor Signaling in Prostate Cancer
We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that treatment with a small-molecule Sigma1 inhibitor prevented 5α- dihydrotestosterone-mediated nuclear translocation of AR and induced proteasomal degradation of AR and ARV, suppressing the transcriptional activity and protein levels of both full-length and splice-variant AR. Consistent with these data, RNAi knockdown of Sigma1 resulted in decreased A...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Jeffrey D. Thomas, Charles G. Longen, Halley M. Oyer, Nan Chen, Christina M. Maher, Joseph M. Salvino, Blase Kania, Kelsey N. Anderson, William F. Ostrander, Karen E. Knudsen, Felix J. Kim Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
