Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer
Publication date: Available online 23 January 2020Source: Cancer CellAuthor(s): Eric C. Cheung, Gina M. DeNicola, Colin Nixon, Karen Blyth, Christiaan F. Labuschagne, David A. Tuveson, Karen H. VousdenSummaryThe TIGAR protein has antioxidant activity that supports intestinal tissue repair and adenoma development. Using a pancreatic ductal adenocarcinoma (PDAC) model, we show that reactive oxygen species (ROS) regulation by TIGAR supports premalignant tumor initiation while restricting metastasis. Increased ROS in PDAC cells drives a phenotypic switch that increases migration, invasion, and metastatic capacity. This switch ...
Source: Cancer Cell - January 25, 2020 Category: Cancer & Oncology Source Type: research
Cancer Genome Evolutionary Trajectories in Metastasis
Publication date: 13 January 2020Source: Cancer Cell, Volume 37, Issue 1Author(s): Nicolai J. Birkbak, Nicholas McGranahanMetastatic cancer is a major cause of death and remains largely incurable. A better understanding of metastasis is therefore desperately needed to improve prognosis for late-stage disease. Here we survey the landscape of studies exploring the genomics of metastatic cancer. We consider evidence for genomic drivers of metastasis and explore studies investigating modes of metastatic spread. (Source: Cancer Cell)
Source: Cancer Cell - January 14, 2020 Category: Cancer & Oncology Source Type: research
An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates
Publication date: 13 January 2020Source: Cancer Cell, Volume 37, Issue 1Author(s): Jermaine Goveia, Katerina Rohlenova, Federico Taverna, Lucas Treps, Lena-Christin Conradi, Andreas Pircher, Vincent Geldhof, Laura P.M.H. de Rooij, Joanna Kalucka, Liliana Sokol, Melissa García-Caballero, Yingfeng Zheng, Junbin Qian, Laure-Anne Teuwen, Shawez Khan, Bram Boeckx, Els Wauters, Herbert Decaluwé, Paul De Leyn, Johan VansteenkisteSummaryHeterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse), and models (in vivo/in vitro) remains poorly inventoried at the single-cell level. We singl...
Source: Cancer Cell - January 14, 2020 Category: Cancer & Oncology Source Type: research
Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis
Publication date: 13 January 2020Source: Cancer Cell, Volume 37, Issue 1Author(s): Douglas Hanniford, Alejandro Ulloa-Morales, Alcida Karz, Maria Gabriela Berzoti-Coelho, Rana S. Moubarak, Beatriz Sánchez-Sendra, Andreas Kloetgen, Veronica Davalos, Jochen Imig, Pamela Wu, Varshini Vasudevaraja, Diana Argibay, Karin Lilja, Tommaso Tabaglio, Carlos Monteagudo, Ernesto Guccione, Aristotelis Tsirigos, Iman Osman, Iannis Aifantis, Eva HernandoSummaryMetastasis is the primary cause of death of cancer patients. Dissecting mechanisms governing metastatic spread may uncover important tumor biology and/or yield promising therapeuti...
Source: Cancer Cell - January 14, 2020 Category: Cancer & Oncology Source Type: research
Vitamin B6 Addiction in Acute Myeloid Leukemia
Publication date: 13 January 2020Source: Cancer Cell, Volume 37, Issue 1Author(s): Chi-Chao Chen, Bo Li, Scott E. Millman, Cynthia Chen, Xiang Li, John P. Morris, Allison Mayle, Yu-Jui Ho, Evangelia Loizou, Hui Liu, Weige Qin, Hardik Shah, Sara Violante, Justin R. Cross, Scott W. Lowe, Lingbo ZhangSummaryCancer cells rely on altered metabolism to support abnormal proliferation. We performed a CRISPR/Cas9 functional genomic screen targeting metabolic enzymes and identified PDXK—an enzyme that produces pyridoxal phosphate (PLP) from vitamin B6—as an acute myeloid leukemia (AML)-selective dependency. PDXK kinase activity ...
Source: Cancer Cell - January 14, 2020 Category: Cancer & Oncology Source Type: research
Myosin II Reactivation and Cytoskeletal Remodeling as a Hallmark and a Vulnerability in Melanoma Therapy Resistance
Publication date: 13 January 2020Source: Cancer Cell, Volume 37, Issue 1Author(s): Jose L. Orgaz, Eva Crosas-Molist, Amine Sadok, Anna Perdrix-Rosell, Oscar Maiques, Irene Rodriguez-Hernandez, Jo Monger, Silvia Mele, Mirella Georgouli, Victoria Bridgeman, Panagiotis Karagiannis, Rebecca Lee, Pahini Pandya, Lena Boehme, Fredrik Wallberg, Chris Tape, Sophia N. Karagiannis, Ilaria Malanchi, Victoria Sanz-MorenoSummaryDespite substantial clinical benefit of targeted and immune checkpoint blockade-based therapies in melanoma, resistance inevitably develops. We show cytoskeletal remodeling and changes in expression and activity ...
Source: Cancer Cell - January 14, 2020 Category: Cancer & Oncology Source Type: research
Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway
Publication date: 13 January 2020Source: Cancer Cell, Volume 37, Issue 1Author(s): Kari J. Kurppa, Yao Liu, Ciric To, Tinghu Zhang, Mengyang Fan, Amir Vajdi, Erik H. Knelson, Yingtian Xie, Klothilda Lim, Paloma Cejas, Andrew Portell, Patrick H. Lizotte, Scott B. Ficarro, Shuai Li, Ting Chen, Heidi M. Haikala, Haiyun Wang, Magda Bahcall, Yang Gao, Sophia ShalhoutSummaryEradicating tumor dormancy that develops following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of EGFR-mutant non-small cell lung cancer, is an attractive therapeutic strategy but the mechanisms governing this process are...
Source: Cancer Cell - January 14, 2020 Category: Cancer & Oncology Source Type: research
Loss or Inhibition of Stromal-Derived PlGF Prolongs Survival of Mice with Imatinib-Resistant Bcr-Abl1+ Leukemia
Publication date: 13 January 2020Source: Cancer Cell, Volume 37, Issue 1Author(s): Thomas Schmidt, Behzad Kharabi Masouleh, Sonja Loges, Sandra Cauwenberghs, Peter Fraisl, Christa Maes, Bart Jonckx, Kim De Keersmaecker, Maria Kleppe, Marc Tjwa, Thomas Schenk, Stefan Vinckier, Rita Fragoso, Maria De Mol, Karolien Beel, Sérgio Dias, Catherine Verfaillie, Richard E. Clark, Tim H. Brümmendorf, Peter Vandenberghe (Source: Cancer Cell)
Source: Cancer Cell - January 14, 2020 Category: Cancer & Oncology Source Type: research
CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer
Publication date: Available online 26 December 2019Source: Cancer CellAuthor(s): Hua Zhang, Camilla L. Christensen, Ruben Dries, Matthew G. Oser, Jiehui Deng, Brian Diskin, Fei Li, Yuanwang Pan, Xuzhu Zhang, Yandong Yin, Eleni Papadopoulos, Val Pyon, Cassandra Thakurdin, Nicholas Kwiatkowski, Kandarp Jani, Alexandra R. Rabin, Dayanne M. Castro, Ting Chen, Heather Silver, Qingyuan HuangSummaryCyclin-dependent kinase 7 (CDK7) is a central regulator of the cell cycle and gene transcription. However, little is known about its impact on genomic instability and cancer immunity. Using a selective CDK7 inhibitor, YKL-5-124, we dem...
Source: Cancer Cell - December 28, 2019 Category: Cancer & Oncology Source Type: research
Pangenomic Classification of Pituitary Neuroendocrine Tumors
We report a comprehensive pangenomic classification of PitNETs. PitNETs from POU1F1/PIT1 lineage showed an epigenetic signature of diffuse DNA hypomethylation, with transposable elements expression and chromosomal instability (except for GNAS-mutated somatotrophs). In TPIT lineage, corticotrophs were divided into three classes: the USP8-mutated with overt secretion, the USP8-wild-type with increased invasiveness and increased epithelial-mesenchymal transition, and the large silent tumors with gonadotroph transdifferentiation. Unexpected expression of gonadotroph markers was also found in GNAS-wild-type somatotrophs (SF1 e...
Source: Cancer Cell - December 28, 2019 Category: Cancer & Oncology Source Type: research
Adenosine Metabolism: Emerging Concepts for Cancer Therapy
Publication date: 9 December 2019Source: Cancer Cell, Volume 36, Issue 6Author(s): Detlev Boison, Gennady G. YegutkinAdenosine is a key metabolic and immune-checkpoint regulator implicated in the tumor escape from the host immune system. Major gaps in knowledge that impede the development of effective adenosine-based therapeutics include: (1) lack of consideration of redundant pathways controlling ATP and adenosine levels; (2) lack of distinction between receptor-dependent and -independent effects of adenosine, and (3) focus on extracellular adenosine without consideration of intracellular metabolism and compartmentalizati...
Source: Cancer Cell - December 10, 2019 Category: Cancer & Oncology Source Type: research
A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia
Publication date: 9 December 2019Source: Cancer Cell, Volume 36, Issue 6Author(s): Andrei V. Krivtsov, Kathryn Evans, Jayant Y. Gadrey, Benjamin K. Eschle, Charlie Hatton, Hannah J. Uckelmann, Kenneth N. Ross, Florian Perner, Sarah N. Olsen, Tara Pritchard, Lisa McDermott, Connor D. Jones, Duohui Jing, Ali Braytee, Diego Chacon, Eric Earley, Brian M. McKeever, David Claremon, Andrew J. Gifford, Heather J. LeeSummaryInhibition of the Menin (MEN1) and MLL (MLL1, KMT2A) interaction is a potential therapeutic strategy for MLL-rearranged (MLL-r) leukemia. Structure-based design yielded the potent, highly selective, and orally b...
Source: Cancer Cell - December 10, 2019 Category: Cancer & Oncology Source Type: research
Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair
Publication date: 9 December 2019Source: Cancer Cell, Volume 36, Issue 6Author(s): Jianhui Ma, Jorge A. Benitez, Jie Li, Shunichiro Miki, Claudio Ponte de Albuquerque, Thais Galatro, Laura Orellana, Ciro Zanca, Rachel Reed, Antonia Boyer, Tomoyuki Koga, Nissi M. Varki, Tim R. Fenton, Suely Kazue Nagahashi Marie, Erik Lindahl, Timothy C. Gahman, Andrew K. Shiau, Huilin Zhou, John DeGroot, Erik P. Sulman (Source: Cancer Cell)
Source: Cancer Cell - December 10, 2019 Category: Cancer & Oncology Source Type: research
Protein Kinase Cι and Wnt/β-Catenin Signaling: Alternative Pathways to Kras/Trp53-Driven Lung Adenocarcinoma
Publication date: 9 December 2019Source: Cancer Cell, Volume 36, Issue 6Author(s): Ning Yin, Yi Liu, Andras Khoor, Xue Wang, E. Aubrey Thompson, Michael Leitges, Verline Justilien, Capella Weems, Nicole R. Murray, Alan P. Fields (Source: Cancer Cell)
Source: Cancer Cell - December 10, 2019 Category: Cancer & Oncology Source Type: research
HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice
Publication date: Available online 27 November 2019Source: Cancer CellAuthor(s): Huacheng Luo, Ganqian Zhu, Jianfeng Xu, Qian Lai, Bowen Yan, Ying Guo, Tsz Kan Fung, Bernd B. Zeisig, Ya Cui, Jie Zha, Christopher Cogle, Fei Wang, Bing Xu, Feng-Chun Yang, Wei Li, Chi Wai Eric So, Yi Qiu, Mingjiang Xu, Suming HuangSummaryLong non-coding RNAs (lncRNAs) are critical for regulating HOX genes, aberration of which is a dominant mechanism for leukemic transformation. How HOX gene-associated lncRNAs regulate hematopoietic stem cell (HSC) function and contribute to leukemogenesis remains elusive. We found that HOTTIP is aberrantly ac...
Source: Cancer Cell - November 28, 2019 Category: Cancer & Oncology Source Type: research
