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  • Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer Is Associated with Indigenous American Ancestry in Latin American Women
    Cancer Res. (IF 8.378) Pub Date : 2020-04-03
    Katie M. Marker; Valentina A. Zavala; Tatiana Vidaurre; Paul C. Lott; Jeannie Navarro Vásquez; Sandro Casavilca-Zambrano; Mónica Calderón; Julio E. Abugattas; Henry L. Gómez; Hugo A. Fuentes; Ruddy Liendo Picoaga; Jose M. Cotrina; Silvia P. Neciosup; Carlos A. Castañeda; Zaida Morante; Fernando Valencia; Javier Torres; Magdalena Echeverry; Mabel E. Bohórquez; Guadalupe Polanco-Echeverry; Ana P. Estrada-Florez;

    Women of Latin American origin in the United States are more likely to be diagnosed with advanced breast cancer and have a higher risk of mortality than non-Hispanic White women. Studies in U.S. Latinas and Latin American women have reported a high incidence of HER2 positive (+) tumors; however, the factors contributing to this observation are unknown. Genome-wide genotype data for 1,312 patients from

    更新日期:2020-04-03
  • Molecular Imaging of the Tumor Microenvironment reveals the Relationship between Tumor Oxygenation, Glucose Uptake and Glycolysis in Pancreatic Ductal Adenocarcinoma
    Cancer Res. (IF 8.378) Pub Date : 2020-04-03
    Kazutoshi Yamamoto; Jeffery R Brender; Tomohiro Seki; Shun Kishimoto; Nobu Oshima; Rajani Choudhuri; Stephen S Adler; Elaine Jagoda; Keita Saito; Nallathamby Devasahayam; Peter L. Choyke; James B Mitchell; Murali C. Krishna

    Molecular imaging approaches for metabolic and physiological imaging of tumors have become important for treatment planning and response monitoring. However, the relationship between the physiological and metabolic aspects of tumors is not fully understood. Here, we developed new hyperpolarized MRI and EPR imaging procedures that allow more direct assessment of tumor glycolysis and oxygenation status

    更新日期:2020-04-03
  • Rapalog-mediated repression of Tribbles pseudokinase 3 regulates pre-mRNA splicing
    Cancer Res. (IF 8.378) Pub Date : 2020-04-03
    Bojana Stefanovska; Cecile Edith Vicier; Thibault Dayris; Vasily Ogryzko; Veronique Scott; Ibrahim Bouakka; Suzette Delaloge; Anna Rocca; Olivia Le Saux; Olivier Trédan; Thomas Bachelot; Fabrice André; Olivia Fromigué

    Rapalogs have become standard of care in patients with metastatic breast, kidney, and neuroendocrine cancers. Nevertheless, tumor escape occurs after several months in most patients, highlighting the need to understand mechanisms of resistance. Using a panel of cancer cell lines, we show that rapalogs downregulate the putative protein kinase TRIB3. Blood samples of a small cohort of cancer patients

    更新日期:2020-04-03
  • Activation of a Subset of Evolutionarily Young Transposable Elements and Innate Immunity are Linked to Clinical Responses to 5-Azacytidine
    Cancer Res. (IF 8.378) Pub Date : 2020-04-03
    Hitoshi Ohtani; Andreas Due Ørskov; Alexandra S Helbo; Linn Gillberg; Minmin Liu; Wanding Zhou; Johanna Ungerstedt; Eva Hellström-Lindberg; Weili Sun; Gangning Liang; Peter A Jones; Kirsten Grønbæk

    The DNA methyltransferase inhibitors (DNMTi) 5-azacytidine (AZA) and 5-aza-2-deoxycytidine have been approved for the treatment of different types of hematological malignancies. However, only about 50% of patients respond to treatment. Therefore, a more comprehensive understanding of the molecular changes in patients treated with DNMTi is needed. Here we examined gene expression profiles in a total

    更新日期:2020-04-03
  • The influence of cancer molecular subtypes and treatment on the mutation spectrum in metastatic breast cancers
    Cancer Res. (IF 8.378) Pub Date : 2020-04-03
    Benjamin Verret; Tony Sourisseau; Bojana Stefanovska; Fernanda Mosele; Alicia Tran-Dien; Fabrice André

    Next-generation sequencing has sparked the exploration of cancer genomes with the aim of discovering the genetic etiology of the disease and proposing rationally designed therapeutic interventions. Driver gene alterations have been comprehensively charted, but the improvement of cancer patient management somewhat lags behind these basic breakthroughs. Recently, large-scale sequencing that focused on

    更新日期:2020-04-03
  • Highlights from Recent Cancer Literature
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    American Association for Cancer Research

    ![][1] Caspase-8 is a key apoptotic mediator and its expression is lost in many tumor types. Paradoxically, caspase-8 is highly expressed in a subset of tumors. Müller and colleagues identified a novel prosurvival function for nuclear caspase-8 that facilitates bypass of a p53-

    更新日期:2020-04-03
  • Platelet RNA as pan-tumor biomarker for cancer detection.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Thomas Wurdinger,Sjors G J G In 't Veld,Myron G Best

    Blood-based liquid biopsies are considered a screening approach for early cancer detection. Sequencing technologies enable in-depth analyses of nucleic acids, including mutant cell-free (cf) DNA in the plasma. However, in blood of patients with early-stage cancer the detection level of mutant cfDNA is relatively low, and complicated by the natural presence of non-cancer cfDNA mutants attributed to

    更新日期:2020-04-03
  • Skipping nonsense to maintain function: the paradigm of BRCA2 exon 12.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Laëtitia Meulemans,Romy L S Mesman,Sandrine M Caputo,Sophie Krieger,Marine Guillaud-Bataille,Virginie Caux-Moncoutier,Mélanie Léone,Nadia Boutry-Kryza,Johanna Sokolowska,Françoise Révillion,Capucine Delnatte,Hélène Tubeuf,Omar Soukarieh,Françoise Bonnet-Dorion,Virginie Guibert,Myriam Bronner,Violaine Bourdon,Sarab Lizard,Paul Vilquin,Maud Privat,Aurélie Drouet,Charlotte Grout,Fabienne M G R Calléja

    Germline nonsense and canonical splice site variants identified in disease-causing genes are generally considered as loss-of-function (LoF) alleles and classified as pathogenic. However, a fraction of such variants could maintain function through their impact on RNA splicing. To test this hypothesis, we used the alternatively spliced BRCA2 exon 12 (E12) as a model system since its in-frame skipping

    更新日期:2020-04-03
  • Inhibition of BCL2 family members increases the efficacy of copper chelation in BRAFV600E-driven melanoma.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Ye-Jin Kim,Tiffany Tsang,Grace R Anderson,Jessica M Posimo,Donita C Brady

    The principal unmet need in BRAFV600E-positive melanoma is lack of an adequate therapeutic strategy capable of overcoming resistance to clinically approved targeted therapies against oncogenic BRAF and/or the downstream MEK1/2 kinases. We previously discovered that copper (Cu) is required for MEK1 and MEK2 activity through a direct Cu-MEK1/2 interaction. Repurposing the clinical Cu chelator tetrathiomolybdate

    更新日期:2020-04-03
  • Dual Oxidase-Induced Sustained Generation of Hydrogen Peroxide Contributes to Pharmacological Ascorbate-Induced Cytotoxicity.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Adrienne R Gibson,Brianne R O'Leary,Juan Du,Ehab H Sarsour,Amanda L Kalen,Brett A Wagner,Jeffrey M Stolwijk,Kelly C Falls-Hubert,Matthew S Alexander,Rory S Carroll,Douglas R Spitz,Garry R Buettner,Prabhat C Goswami,Joseph J Cullen

    Pharmacological ascorbate treatment (P-AscH-, high-dose, intravenous vitamin C) results in a transient short-term increase in the flux of hydrogen peroxide that is preferentially cytotoxic to cancer cells vs. normal cells. This study examines whether an increase in hydrogen peroxide is sustained post-treatment and potential mechanisms involved in this process. Cellular bioenergetic profiling following

    更新日期:2020-04-03
  • UBR5 is co-amplified with MYC in breast tumors and encodes an ubiquitin ligase that limits MYC-dependent apoptosis.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Xi Qiao,Ying Liu,Maria Llamazares Prada,Aravind Kumar Mohan,Abhishekh Gupta,Alok Jaiswal,Mukund Sharma,Joni Merisaari,Heidi M Haikala,Kati Talvinen,Laxman Yetukuri,Joanna W Pylvänäinen,Juha Klefström,Pauliina Kronqvist,Annika Meinander,Tero Aittokallio,Ville Hietakangas,Martin Eilers,Jukka Westermarck

    For maximal oncogenic activity, cellular MYC protein levels need to be tightly controlled so that they do not induce apoptosis. Here, we show how ubiquitin ligase UBR5 functions as a molecular rheostat to prevent excess accumulation of MYC protein. UBR5 ubiquitinates MYC, and its effects on MYC protein stability are independent of FBXW7. Silencing of endogenous UBR5 induced MYC protein expression and

    更新日期:2020-04-03
  • Oncogenic ERG represses PI3K signaling through down-regulation of IRS2.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Ninghui Mao,Dong Gao,Wenhuo Hu,Sunyana Gadal,Haley Hieronymus,Shangqian Wang,Young Sun Lee,Patrick Sullivan,Zeda Zhang,Danielle Choi,Neal Rosen,Charles L Sawyers,Anuradha Gopalan,Yu Chen,Brett S Carver

    Genomic rearrangements leading to the aberrant expression of ERG are the most common early events in prostate cancer and are significantly enriched for the concomitant loss of PTEN. Genetically engineered mouse models reveal that ERG overexpression alone is not sufficient to induce tumorigenesis, but combined loss of PTEN results in an aggressive invasive phenotype. Here we show that oncogenic ERG

    更新日期:2020-04-03
  • Enhanced lipid accumulation and metabolism are required for the differentiation and activation of tumor-associated macrophages.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Pan Su,Qiang Wang,Enguang Bi,Xingzhe Ma,Lintao Liu,Maojie Yang,Jianfei Qian,Qing Yi

    Tumor-associated macrophages (TAMs) are important tumor-promoting cells. However, the mechanism underlying how tumor and its microenvironment reprogram these cells remains elusive. Here we report that lipids play a crucial role in TAM generation in tumor microenvironment. Macrophages from both human and murine tumor tissues are enriched with lipids as a result of increased lipid uptake by macrophages

    更新日期:2020-04-03
  • In silico models accurately predict in vivo response for IL-6 blockade in head and neck cancer.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Fereshteh Nazari,Alexandra E Oklejas,Jacques E Nör,Alexander T Pearson,Trachette L Jackson

    Malignant features of head and neck squamous cell carcinoma (HNSCC) may be derived from the presence of stem-like cells that are characterized by uniquely high tumorigenic potential. These cancer stem cells (CSCs) function as putative drivers of tumor initiation, therapeutic evasion, metastasis, and recurrence. Though they are an appealing conceptual target, CSC-directed cancer therapies remain scarce

    更新日期:2020-04-03
  • Cancer Cell-Derived Matrisome Proteins Promote Metastasis in Pancreatic Ductal Adenocarcinoma.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Chenxi Tian,Daniel Öhlund,Steffen Rickelt,Tommy Lidström,Ying Huang,Liangliang Hao,Renee T Zhao,Oskar Franklin,Sangeeta N Bhatia,David A Tuveson,Richard O Hynes

    The prognosis for pancreatic ductal adenocarcinoma (PDAC) remains poor despite decades of effort. The abundant extracellular matrix (ECM) in PDAC comprises a major fraction of the tumor mass and plays various roles in promoting resistance to therapies. However, nonselective depletion of ECM has led to poor patient outcomes. Consistent with that observation, we previously showed that individual matrisome

    更新日期:2020-04-03
  • Proteomic Profiling of the ECM of Xenograft Breast Cancer Metastases in Different Organs Reveals Distinct Metastatic Niches.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Jess D Hebert,Samuel A Myers,Alexandra Naba,Genevieve Abbruzzese,John M Lamar,Steven A Carr,Richard O Hynes

    Metastasis causes most cancer-related deaths, and one poorly understood aspect of metastatic cancer is the adaptability of cells from a primary tumor to create new niches and survive in multiple, different secondary sites. We used quantitative mass spectrometry to analyze the extracellular matrix (ECM), a critical component of metastatic niches, in metastases to the brain, lungs, liver, and bone marrow

    更新日期:2020-04-03
  • Truncated ASPP2 drives initiation and progression of invasive lobular carcinoma via distinct mechanisms.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Koen Schipper,Anne Paulien Drenth,Eline van der Burg,Samuel P Cornelissen,Sjoerd Klarenbeek,Micha Nethe,Jos Jonkers

    Invasive lobular carcinoma (ILC) accounts for 8-14% of all breast cancer cases. The main hallmark of ILCs is the functional loss of the cell-cell adhesion protein E-cadherin. Nonetheless, loss of E-cadherin alone does not predispose mice to mammary tumor development indicating that additional perturbations are required for ILC formation. Previously, we identified an N-terminal truncation variant of

    更新日期:2020-04-03
  • Clonal ZEB1-driven mesenchymal transition promotes targetable oncologic anti-angiogenic therapy resistance.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Ankush Chandra,Arman Jahangiri,William Chen,Alan T Nguyen,Garima Yagnik,Matheus P Pereira,Saket Jain,Joseph H Garcia,Sumedh S Shah,Harsh Wadhwa,Rushikesh S Joshi,Jacob Weiss,Kayla J Wolf,Jung-Ming G Lin,Sören Müller,Jonathan W Rick,Aaron A Diaz,Luke A Gilbert,Sanjay Kumar,Manish K Aghi

    Glioblastoma responses to bevacizumab are invariably transient with acquired resistance. We profiled paired patient specimens and bevacizumab-resistant xenograft models pre- and post-resistance towards the primary goal of identifying regulators whose targeting could prolong the therapeutic window, and the secondary goal of identifying biomarkers of therapeutic window closure. Bevacizumab-resistant

    更新日期:2020-04-03
  • Extensive clonal branching shapes the evolutionary history of high-risk pediatric cancers.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Natalie Andersson,Bjorn Bakker,Jenny Karlsson,Anders Valind,Linda Holmquist Mengelbier,Diana C J Spierings,Floris Foijer,David Gisselsson

    Darwinian evolution of tumor cells remains underexplored in childhood cancer. We here reconstruct the evolutionary histories of 56 pediatric primary tumors, including 24 neuroblastomas, 24 Wilms tumors and 8 rhabdomyosarcomas. Whole genome copy number and whole exome mutational profiling of multiple regions per tumor was performed followed by clonal deconvolution to reconstruct a phylogenetic tree

    更新日期:2020-04-03
  • An ABC transporter drives medulloblastoma pathogenesis by regulating Sonic Hedgehog signaling.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Juwina Wijaya,BaoHan T Vo,Jingjing Liu,Beisi Xu,Gang Wu,Yao Wang,Junmin Peng,Jin Zhang,Laura J Janke,Brent A Orr,Jiyang Yu,Martine F Roussel,John D Schuetz

    Mutations in Sonic hedgehog (SHH) signaling promote aberrant proliferation and tumor growth. SHH medulloblastoma (MB) is among the most frequent brain tumors in children less than three years of age. While key components of the SHH pathway are well-known, we hypothesized that new disease-modifying targets of SHH MB might be identified from large-scale bioinformatics and systems biology analyses. Using

    更新日期:2020-04-03
  • Thermal proteome profiling identifies oxidative-dependent inhibition of the transcription of major oncogenes as a new therapeutic mechanism for select anticancer compounds.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Sylvain Peuget,Jiawei Zhu,Gema Sanz,Madhurendra Singh,Massimiliano Gaetani,Xinsong Chen,Yao Shi,Amir Ata Saei,Torkild Visnes,Mikael S Lindström,Ali Rihani,Lidia Moyano-Galceran,Joseph W Carlson,Elisabet Hjerpe,Ulrika Joneborg,Kaisa Lehti,Johan Hartman,Thomas Helleday,Roman Zubarev,Galina Selivanova

    Identification of the molecular mechanism of action (MoA) of bioactive compounds is a crucial step for drug development but remains a challenging task despite recent advances in technology. In this study, we applied multidimensional proteomics, sensitivity correlation analysis and transcriptomics to identify a common mechanism of action for the anticancer compounds RITA, aminoflavone (AF) and oncrasin-1

    更新日期:2020-04-03
  • Single-cell Proteomic Profiling Identifies Combined AXL and JAK1 Inhibition as a Novel Therapeutic Strategy for Lung Cancer.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Josephine A Taverna,Chia-Nung Hung,Daniel T DeArmond,Meizhen Chen,Chun-Lin Lin,Pawel A Osmulski,Maria E Gaczynska,Chiou-Miin Wang,Nicholas D Lucio,Chih-Wei Chou,Chun-Liang Chen,Alia Nazarullah,Shellye R Lampkin,Lianqun Qiu,David J Bearss,Steven Warner,Clifford J Whatcott,Lars Mouritsen,Mark Wade,Steven Weitman,Ruben A Mesa,Nameer B Kirma,Wei-Ting Chao,Tim H-M Huang

    Cytometry by time-of-flight (CyTOF) simultaneously measures multiple cellular proteins at the single-cell level and is used to assess inter- and intra-tumor heterogeneity. This approach may be used to investigate the variability of individual tumor responses to treatments. Herein, we stratified lung tumor subpopulations based on AXL signaling as a potential targeting strategy. Integrative transcriptome

    更新日期:2020-04-03
  • Modeling acquired resistance to the second-generation androgen receptor antagonist enzalutamide in the TRAMP model of prostate cancer.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Marianna Cerasuolo,Federica Maccarinelli,Daniela Coltrini,Ali Mokhtar Mahmoud,Viviana Marolda,Gaia Cristina Ghedini,Sara Rezzola,Arianna Giacomini,Luca Triggiani,Magdalena Kostrzewa,Roberta Verde,Debora Paris,Dominique Melck,Marco Presta,Alessia Ligresti,Roberto Ronca

    Enzalutamide (MDV3100) is a potent second-generation androgen receptor antagonist approved for the treatment of castration-resistant prostate cancer (CRPC) in chemotherapy-naïve as well as in patients previously exposed to chemotherapy. However, resistance to enzalutamide and enzalutamide withdrawal syndrome have been reported. Thus, reliable and integrated preclinical models are required to elucidate

    更新日期:2020-04-03
  • Towards Multidrug Adaptive Therapy.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Jeffrey West,Li You,Jingsong Zhang,Robert A Gatenby,Joel S Brown,Paul K Newton,Alexander R A Anderson

    A new ecologically inspired paradigm in cancer treatment known as "adaptive therapy" capitalizes on competitive interactions between drug-sensitive and drug-resistant subclones. The goal of adaptive therapy is to maintain a controllable stable tumor burden by allowing a significant population of treatment-sensitive cells to survive. These, in turn, suppress proliferation of the less-fit resistant populations

    更新日期:2020-04-03
  • Heritability of Mammographic Breast Density, Density Change, Microcalcifications, and Masses
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Natalie Holowko; Mikael Eriksson; Ralf Kuja-Halkola; Shadi Azam; Wei He; Per Hall; Kamila Czene

    Mammographic features influence breast cancer risk and are used in risk prediction models. Understanding how genetics influence mammographic features is important because the mechanisms through which they are associated with breast cancer are not well known. Here, using mammographic screening history and detailed questionnaire data from 56,820 women from the KARMA prospective cohort study, we investigated

    更新日期:2020-04-03
  • Across-site differences in the mechanism of alcohol-induced digestive tract carcinogenesis: an evaluation by mediation analysis.
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Yuriko N Koyanagi,Etsuji Suzuki,Issei Imoto,Yumiko Kasugai,Isao Oze,Tomotaka Ugai,Madoka Iwase,Yoshiaki Usui,Yukino Kawakatsu,Michi Sawabe,Yutaka Hirayama,Tsutomu Tanaka,Tetsuya Abe,Seiji Ito,Koji Komori,Nobuhiro Hanai,Masahiro Tajika,Yasuhiro Shimizu,Yasumasa Niwa,Hidemi Ito,Keitaro Matsuo

    A genetic variant on Aldehyde dehydrogenase 2 (ALDH2 rs671, Glu504Lys) contributes to carcinogenesis after alcohol consumption. Somewhat conversely, the ALDH2 Lys allele also confers a protective effect against alcohol-induced carcinogenesis, by decreasing alcohol consumption due to acetaldehyde-related adverse effects. Here, we applied a mediation analysis to five case-control studies for head and

    更新日期:2020-04-03
  • Editor's Note: p73 and p63 Sustain Cellular Growth by Transcriptional Activation of Cell Cycle Progression Genes
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Konstantinos Lefkimmiatis; Mariano Francesco Caratozzolo; Paola Merlo; Anna Maria D'Erchia; Beatriz Navarro; Massimo Levrero; Elisabetta Sbisa'; Apollonia Tullo

    The editors are publishing this note to alert readers to a concern about [this article][1] ([1][2]). The authors made the editors aware of duplicated Western blot bands in Fig. 3. Specifically, the same image was used for the actin loading control Western blot bands for the ADA and FASN experiments

    更新日期:2020-04-03
  • Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy
    Cancer Res. (IF 8.378) Pub Date : 2020-04-01
    Daniel R Principe; Matthew Narbutis; Sandeep Kumar; Alex Park; Navin Viswakarma; Matthew J Dorman; Suneel D Kamath; Paul J Grippo; Melissa L Fishel; Rosa F. Hwang; Dinesh Thummuri; Patrick W Underwood; Hidayatullah G. Munshi; Jose G. Trevino; Ajay Rana

    Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death with a median survival time of 6-12 months. Most patients present with disseminated disease and the majority are offered palliative chemotherapy. With no approved treatment modalities for patients who progress on chemotherapy, we explored the effects of long-term Gemcitabine on the tumor microenvironment in order to

    更新日期:2020-04-01
  • MAFB promotes cancer stemness and tumorigenesis in osteosarcoma through a Sox9-mediated positive feedback loop
    Cancer Res. (IF 8.378) Pub Date : 2020-03-31
    Yanyan Chen; Bin Wang; Mengxi Huang; Tao Wang; Chao Hu; Qin Liu; Dong Han; Cheng Chen; Junliang Zhang; Zhiping Li; Chao Liu; Wenbin Lei; Yue Chang; Meijuan Wu; Dan Xiang; Yitian Chen; Rui Wang; Weiqian Huang; Zengjie Lei; Xiaoyuan Chu

    Despite the fact that osteosarcoma is one of the most common primary bone malignancies with poor prognosis, the mechanism behind the pathogenesis of osteosarcoma is only partially known. Here we characterized differentially expressed genes (DEG) by extensive analysis of several publicly available gene expression profile datasets and identified MAFB as a key transcriptional regulator in osteosarcoma

    更新日期:2020-03-31
  • Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease
    Cancer Res. (IF 8.378) Pub Date : 2020-03-27
    Christopher Gromisch; Motaz Qadan; Mariana Albuquerque Machado; Kebin Liu; Yolonda Colson; Mark W. Grinstaff

    This review highlights current treatments, limitations, and pitfalls in the management of pancreatic cancer and discusses current research in novel targets and drug development to overcome these clinical challenges. We begin with a review of the clinical landscape of pancreatic cancer, including genetic and environmental risk factors, as well as limitations in disease diagnosis and prevention. We next

    更新日期:2020-03-27
  • Hybrid epithelial-mesenchymal phenotypes are controlled by microenvironmental factors
    Cancer Res. (IF 8.378) Pub Date : 2020-03-26
    Gianluca Selvaggio; Sara Canato; Archana Pawar; Pedro T Monteiro; Patrícia S. Guerreiro; M. Manuela Brás; Florence Janody; Claudine Chaouiya

    Epithelial-to-mesenchymal transition (EMT) has been associated with cancer cell heterogeneity, plasticity, and metastasis. However, the extrinsic signals supervising these phenotypic transitions remain elusive. To assess how selected microenvironmental signals control cancer-associated phenotypes along the EMT continuum, we defined a logical model of the EMT cellular network that yields qualitative

    更新日期:2020-03-27
  • USP10 Promotes Proliferation of Hepatocellular Carcinoma by Deubiquitinating and Stabilizing YAP/TAZ
    Cancer Res. (IF 8.378) Pub Date : 2020-03-26
    Hong Zhu; Fangjie Yan; Tao Yuan; Meijia Qian; Tianyi Zhou; Xiaoyang Dai; Ji Cao; Meidan Ying; Xiaowu Dong; Qiaojun He; Bo Yang

    Yes-associated protein (YAP) and its paralogue, transcriptional co-activator with PDZ-binding motif (TAZ), play pivotal roles in promoting the progression of hepatocellular carcinoma (HCC). However, the regulatory mechanism underpinning aberrant activation of YAP/TAZ in HCC remains unclear. In this study, we globally profiled the contribution of deubiquitinating enzymes (DUB) to both transcriptional

    更新日期:2020-03-27
  • CircFOXK2 Promotes Growth and Metastasis of Pancreatic Ductal Adenocarcinoma by Complexing with RNA Binding Proteins and Sponging MiR-942
    Cancer Res. (IF 8.378) Pub Date : 2020-03-26
    Chi Hin Wong; Ut Kei Lou; Youjia Li; Stephen L. Chan; Joanna H.M. Tong; Ka-Fai To; Yangchao Chen

    The detailed biological functions of circular RNA (circRNA) are largely unexplored. Using circRNA sequencing, we identified 169 differentially expressed circRNA in pancreatic ductal adenocarcinoma (PDAC) cells compared to non-tumor human pancreatic ductal epithelial (HPDE) cells. Among them, circFOXK2 was validated with significant upregulation in PDAC cells and 63 % of primary tumors (53 out of 84)

    更新日期:2020-03-27
  • RNF168-mediated ubiquitin signaling inhibits the viability of BRCA1 null cancers
    Cancer Res. (IF 8.378) Pub Date : 2020-03-25
    John J. Krais; Yifan Wang; Andrea J. Bernhardy; Emma Clausen; Jessica A. Miller; Kathy Q. Cai; Clare L. Scott; Neil Johnson

    BRCA1 gene mutations impair homologous recombination (HR) DNA repair, resulting in cellular senescence and embryonic lethality in mice. Therefore, BRCA1-deficient cancers require adaptations that prevent excessive genomic alterations from triggering cell death. RNF168-mediated ubiquitination of γH2AX at K13/15 (ub-H2AX) serves as a recruitment module for the localization of 53BP1 to DNA break sites

    更新日期:2020-03-26
  • Consumption of the fish oil high-fat diet uncouples obesity and mammary tumor growth through induction of reactive oxygen species in pro-tumor macrophages
    Cancer Res. (IF 8.378) Pub Date : 2020-03-25
    Lianliang Liu; Rong Jin; Jiaqing Hao; Jun Zeng; Di Yin; Yanmei Yi; Mingming Zhu; Anita Mandal; Yuan Hua; Chin K. Ng; Nejat K Egilmez; Edward R. Sauter; Bing Li

    Obesity is associated with increased risk of many types of cancer and can be induced by various high-fat diets (HFD) from different fat sources. It remains unknown whether fatty acid composition in different HFD influences obesity-associated tumor development. Here we report that consumption of either a cocoa butter or fish oil HFD induced similar obesity in mouse models. While obesity induced by the

    更新日期:2020-03-26
  • PSF promotes ER-positive breast cancer progression via posttranscriptional regulation of ESR1 and SCFD2
    Cancer Res. (IF 8.378) Pub Date : 2020-03-25
    Yuichi Mitobe; Kaori Iino; Ken-ichi Takayama; Kazuhiro Ikeda; Takashi Suzuki; Kenjiro Aogi; Hidetaka Kawabata; Yutaka Suzuki; Kuniko Horie-Inoue; Satoshi Inoue

    Endocrine therapy is standard treatment for estrogen receptor (ER)-positive breast cancer, yet long-term treatment often causes acquired resistance, which results in recurrence and metastasis. Recent studies have revealed that RNA-binding proteins (RBP) are involved in tumorigenesis. Here we demonstrate that PSF/SFPQ is an RBP that potentially predicts poor prognosis of ER-positive breast cancer patients

    更新日期:2020-03-26
  • Loss of APC Rapidly Impairs DNA Methylation Programs and Cell Fate Decisions in LGR5+ Intestinal Stem Cells
    Cancer Res. (IF 8.378) Pub Date : 2020-03-25
    Marco Bruschi; Laure Garnier; Elouan Cleroux; Alicia Giordano; Michael Dumas; Anaïs F Bardet; Thomas Kergrohen; Stanislas Quesada; Pierre Cesses; Michael Weber; François Gerbe; Philippe Jay

    Colorectal cancer (CRC) initiation and progression result from the accumulation of genetic and epigenetic alterations. Although aberrant gene expression and DNA methylation profiles are considered hallmarks of CRC development, the precise timing at which these are produced during tumor establishment remains elusive. Here we investigated the early transcriptional and epigenetic changes induced by Apc

    更新日期:2020-03-26
  • The frequency of Ras mutations in cancer
    Cancer Res. (IF 8.378) Pub Date : 2020-03-24
    Ian A Prior; Fiona E Hood; James L Hartley

    Ras is frequently mutated in cancer; however, there is a lack of consensus in the literature regarding the cancer mutation frequency of Ras, with quoted values varying from 10-30%. This variability is at least in part due to the selective aggregation of data from different databases and the dominant influence of particular cancer types and particular Ras isoforms within these datasets. In order to

    更新日期:2020-03-26
  • NOX4 inhibition potentiates immunotherapy by overcoming cancer-associated fibroblast-mediated CD8 T-cell exclusion from tumours.
    Cancer Res. (IF 8.378) Pub Date : 2020-03-02
    Kirsty Ford,Christopher J Hanley,Massimiliano Mellone,Cedric Szyndralewiez,Freddy Heitz,Philippe Wiesel,Oliver Wood,Maria Machado,Maria-Antoinette Lopez,Anusha-Preethi Ganesan,Chuan Wang,Ankur Chakravarthy,Tim R Fenton,Emma V King,Pandurangan Vijayanand,Christian H Ottensmeier,Aymen Al-Shamkhani,Natalia Savelyeva,Gareth J Thomas

    Determining mechanisms of resistance to PD-1/PD-L1 immune checkpoint immunotherapy is key to developing new treatment strategies. Cancer-associated fibroblasts (CAF) have many tumor-promoting functions and promote immune evasion through multiple mechanisms, but as yet, there are no CAF-specific inhibitors clinically available. Here we generated CAF-rich murine tumor models (TC1, MC38, 4T1) to investigate

    更新日期:2020-03-26
  • Endonuclease FEN1 coregulates ERα activity and provides a novel drug interface in tamoxifen resistant breast cancer
    Cancer Res. (IF 8.378) Pub Date : 2020-03-19
    Koen D Flach; Manikandan Periyasamy; Ajit Jadhav; Dorjbal Dorjsuren; Joseph C Siefert; Theresa E Hickey; Mark Opdam; Hetal Patel; Sander Canisius; David M Wilson; Maria Donaldson Collier; Stefan Prekovic; Marja Nieuwland; Roelof JC Kluin; Alexey V Zakharov; Jelle Wesseling; Lodewyk F.A. Wessels; Sabine C Linn; Wayne D Tilley; Anton Simeonov; Simak Ali; Wilbert Zwart

    Estrogen receptor α (ERα) is a key transcriptional regulator in the majority of breast cancers. ERα-positive patients are frequently treated with tamoxifen, but resistance is common. In this study, we refined a previously identified 111-gene outcome prediction-classifier, revealing FEN1 as the strongest determining factor in ERα-positive patient prognostication. FEN1 levels were predictive of outcome

    更新日期:2020-03-20
  • A Feedback loop comprising EGF/TGF-α Sustains TFCP2-mediated Breast Cancer Progression
    Cancer Res. (IF 8.378) Pub Date : 2020-03-19
    Yi Zhao; Neha Kaushik; Jae-Hyeok Kang; Nagendra Kumar Kaushik; Seung Han Son; Nizam Uddin; Min-Jung Kim; Chul Geun Kim; Su-Jae Lee

    Stemness and epithelial-mesenchymal transition (EMT) are two fundamental characteristics of metastasis that are controlled by diverse regulatory factors, including transcription factors. Compared with other subtypes of breast cancer, basal-type or triple-negative breast cancer (TNBC) have high frequencies of tumor relapse. However, the role of alpha-globin transcription factor CP2 (TFCP2) has not been

    更新日期:2020-03-20
  • The interplay between slow-cycling, chemoresistant cancer cells and fibroblasts creates a proinflammatory niche for tumor progression
    Cancer Res. (IF 8.378) Pub Date : 2020-03-19
    Jaebeom Cho; Hyo-Jong Lee; Su Jung Hwang; Hye-Young Min; Han Na Kang; A-Young Park; Seung Yeob Hyun; Jeong Yeon Sim; Ho Jin Lee; Hyun-Ji Jang; Young-Ah Suh; Sungyoul Hong; Young Kee Shin; Hye Ryun Kim; Ho-Young Lee

    Quiescent cancer cells are believed to cause cancer progression after chemotherapy through unknown mechanisms. We show here that human non-small-cell lung cancer (NSCLC) cell line-derived, quiescent-like, slow-cycling cancer cells (SCC) and residual patient-derived xenograft (PDX) tumors after chemotherapy experience activating transcription factor 6 (ATF6)-mediated upregulation of various cytokines

    更新日期:2020-03-20
  • Targeting of CD38 by the tumor suppressor miR-26a serves as a novel potential therapeutic agent in multiple myeloma
    Cancer Res. (IF 8.378) Pub Date : 2020-03-19
    Yi Hu; Huimin Liu; Chuanfeng Fang; Chen Li; Fjorela Xhyliu; Hayley Dysert; Juraj Bodo; Gabriel Habermehl; Benjamin E Russell; Wenjun Li; Marcia Chappell; Xiaofeng Jiang; Sarah L. Ondrejka; Eric D. Hsi; Jaroslaw P Maciejewski; Qing Yi; Kenneth C. Anderson; Nikhil C. Munshi; Geyou Ao; Jason N Valent; Jianhong Lin; Jianjun Zhao

    Multiple myeloma (MM) is an incurable refractory hematological malignancy arising from plasma cells in the bone marrow. Here we investigated miR-26a function in MM and tested single-wall carbon nanotube delivery of miR-26a in vitro and in vivo. miR-26a was downregulated in patient MM cells compared with plasma cells from healthy donors. miR-26a overexpression inhibited proliferation and migration and

    更新日期:2020-03-20
  • Inactivation of the prolyl isomerase Pin1 sensitizes BRCA1-proficient breast cancer to PARP inhibition
    Cancer Res. (IF 8.378) Pub Date : 2020-03-19
    Man-Li Luo; Fang Zheng; Wenying Chen; Zhi-Mei Liang; Gurushankar Chandramouly; Jianan Tan; Nicholas A Willis; Chun-Hau Chen; Mateus de Oliveira Taveira; Xiao Zhen Zhou; Kun Ping Lu; Ralph Scully; Gerburg M. Wulf; Hai Hu

    PARP inhibitor monotherapies effectively treat breast, ovary, prostate, and pancreatic cancer patients with BRCA1 mutations, but not the more frequent BRCA-wildtype cancers. Searching for strategies that would extend the use of PARP inhibitors to BRCA1-proficient tumors, we report here that the stability of BRCA1 protein following ionizing radiation (IR) is maintained by post-phosphorylational prolyl-isomerization

    更新日期:2020-03-20
  • Drug sensitivity and allele-specificity of first-line osimertinib resistance EGFR mutations
    Cancer Res. (IF 8.378) Pub Date : 2020-03-19
    Jacqueline H Starrett; Alexis A Guernet; Maria Emanuela Cuomo; Kamrine E Poels; Iris K van Alderwerelt van Rosenburgh; Amy Nagelberg; Dylan Farnsworth; Kristin S Price; Hina Khan; Kumar Dilip Ashtekar; Mmaserame Gaefele; Deborah Ayeni; Tyler F Stewart; Alexandra Kuhlmann; Susan Kaech; Arun M Unni; Robert Homer; William W Lockwood; Franziska Michor; Sarah B. Goldberg; Mark A. Lemmon; Paul D Smith; Darren

    Osimertinib, a mutant-specific third generation EGFR TKI, is emerging as the preferred first-line therapy for EGFR mutant lung cancer, yet resistance inevitably develops in patients. We modeled acquired resistance to osimertinib in transgenic mouse models of EGFR L858R-induced lung adenocarcinoma and found that it is mediated largely through secondary mutations in EGFR - either C797S or L718V/Q. Analysis

    更新日期:2020-03-20
  • LncSpA: LncRNA Spatial Atlas of Expression across Normal and Cancer Tissues
    Cancer Res. (IF 8.378) Pub Date : 2020-03-19
    Dezhong Lv; Kang Xu; Xiyun Jin; Junyi Li; Yunchen Shi; Mengying Zhang; Xiaoyan Jin; Yongsheng Li; Juan Xu; Xia Li

    Long noncoding RNAs (LncRNA) play important roles in maintaining morphology and function of tissues, and their regulatory effectiveness is closely associated with spatial expression. To provide a comprehensive spatial atlas of expression for lncRNA, we propose LncSpA (http://bio-bigdata.hrbmu.edu.cn/LncSpA) to explore tissue-elevated (TE) lncRNA across human normal and adult and pediatric cancer tissues

    更新日期:2020-03-20
  • The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment
    Cancer Res. (IF 8.378) Pub Date : 2020-03-19
    Casimiro Gerarduzzi; Ursula Hartmann; Andrew Leask; Elliot Drobetsky

    The extracellular matrix (ECM) surrounding cells is indispensable for regulating their behavior. The dynamics of ECM signaling are tightly controlled throughout growth and development. During tissue remodeling, matricellular proteins (MCPs) are secreted into the ECM. These factors do not serve classical structural roles, but rather regulate matrix proteins and cell-matrix interactions to influence

    更新日期:2020-03-20
  • GPD1 enhances the anti-cancer effects of metformin by synergistically increasing total cellular glycerol-3-phosphate
    Cancer Res. (IF 8.378) Pub Date : 2020-03-16
    Jianjiang Xie; Jianheng Ye; Zhiduan Cai; Yong Luo; Xuejin Zhu; Yulin Deng; Yuanfa Feng; Yingke Liang; Ren Liu; Zhaodong Han; Yuxiang Liang; Yu Zheng; Rujun Mo; Yangjia Zhuo; Yongding Wu; Funeng Jiang; Jianguo Zhu; Chin-Lee Wu; Weide Zhong

    Metformin is an oral drug widely used for the treatment of type 2 diabetes mellitus. Numerous studies have demonstrated the value of metformin in cancer treatment. However, for metformin to elicit effects on cancer this often requires a high dosage, and any underlying mechanism for how to improve its inhibitory effects remains unknown. Here we found that low mRNA expression of glycerol-3-phosphate

    更新日期:2020-03-16
  • A feed-forward mechanosignaling loop confers resistance to therapies targeting the MAPK pathway in BRAF-mutant melanoma
    Cancer Res. (IF 8.378) Pub Date : 2020-03-16
    Christophe A Girard; Margaux Lecacheur; Rania Ben Jouira; Ilona Berestjuk; Serena Diazzi; Virginie Prod'homme; Aude Mallavialle; Frédéric Larbret; Maéva Gesson; Sébastien Schaub; Sabrina Pisano; Stéphane Audebert; Bernard Mari; Cédric Gaggioli; Eleonora Leucci; Jean-Christophe Marine; Marcel Deckert; Sophie Tartare-Deckert

    Aberrant extracellular matrix (ECM) deposition and stiffening is a physical hallmark of several solid cancers and is associated with therapy failure. BRAF-mutant melanomas treated with BRAF and MEK inhibitors almost invariably develop resistance that is frequently associated with transcriptional reprogramming and a de-differentiated cell state. Melanoma cells secrete their own ECM proteins, an event

    更新日期:2020-03-16
  • Infiltrating mast cell-mediated stimulation of estrogen receptor activity in breast cancer cells promotes the luminal phenotype
    Cancer Res. (IF 8.378) Pub Date : 2020-03-16
    Maria Teresa Majorini; Valeria Cancila; Alice Rigoni; Laura Botti; Matteo Dugo; Tiziana Triulzi; Loris De Cecco; Enrico Fontanella; Elena Jachetti; Elda Tagliabue; Claudia Chiodoni; Claudio Tripodo; Mario P. Colombo; Daniele Lecis

    Tumor growth and development is determined by both cancer cell-autonomous and microenvironmental mechanisms, including the contribution of infiltrating immune cells. Since the role of mast cells (MC) in this process is poorly characterized and even controversial, we investigated their part in breast cancer (BC). Crossing C57BL/6 MMTV-PyMT mice, which spontaneously develop mammary carcinomas, with MC-deficient

    更新日期:2020-03-16
  • A Novel Micropeptide Encoded by Y-Linked LINC00278 Links Cigarette Smoking and AR Signaling in Male Esophageal Squamous Cell Carcinoma
    Cancer Res. (IF 8.378) Pub Date : 2020-03-13
    Siqi Wu; Liyuan Zhang; Jieqiong Deng; Binbin Guo; Fang Li; Yirong Wang; Rui Wu; Shenghua Zhang; Jiachun Lu; Yifeng Zhou

    Long non-coding RNAs (lncRNA) have been shown to play critical roles in many diseases, including esophageal squamous cell carcinoma (ESCC). Recent studies have reported that some lncRNA encode functional micropeptides. However, the association between ESCC and micropeptides encoded by lncRNA remains largely unknown. In this study, we characterized a Y-linked lncRNA, LINC00278, which was downregulated

    更新日期:2020-03-16
  • Highlights from Recent Cancer Literature
    Cancer Res. (IF 8.378) Pub Date : 2020-03-15
    American Association for Cancer Research

    ![][1] Most EGFR-mutated non-small cell lung cancers are not completely eradicated in response to treatment with EGFR inhibitors, allowing for the eventual development of acquired resistance and cure prevention. Kurppa and colleagues demonstrate that YAP-dependent therapy-induced

    更新日期:2020-03-16
  • Metabolite Imaging at the Margin: Visualizing Metabolic Tumor Gradients Using Mass Spectrometry
    Cancer Res. (IF 8.378) Pub Date : 2020-03-15
    Ai Wen Tan; Aalim M. Weljie

    Glioblastoma multiforme (GBM) tumors are highly metabolic and vascularized, yet little has been reported regarding the spatial localization of metabolic activity within these tumors. A mass spectrometry imaging (MSI) study by Randall and colleagues in this issue provides provocative observations of metabolic gradients in xenograft GBM models. The intensity of acylcarnitines is dramatically increased

    更新日期:2020-03-16
  • ETV4 Is Necessary for Estrogen Signaling and Growth in Endometrial Cancer Cells.
    Cancer Res. (IF 8.378) Pub Date : 2020-02-11
    Adriana C Rodriguez,Jeffery M Vahrenkamp,Kristofer C Berrett,Kathleen A Clark,Katrin P Guillen,Sandra D Scherer,Chieh-Hsiang Yang,Bryan E Welm,Margit M Janát-Amsbury,Barbara J Graves,Jason Gertz

    Estrogen signaling through estrogen receptor alpha (ER) plays a major role in endometrial cancer risk and progression, however, the molecular mechanisms underlying ER's regulatory role in endometrial cancer are poorly understood. In breast cancer cells, ER genomic binding is enabled by FOXA1 and GATA3, but the transcription factors that control ER genomic binding in endometrial cancer cells remain

    更新日期:2020-03-16
  • In Situ DESI-MSI Lipidomic Profiles of Breast Cancer Molecular Subtypes and Precursor Lesions
    Cancer Res. (IF 8.378) Pub Date : 2020-03-15
    Adriana Leandra Santoro; Rodrigo D. Drummond; Israel Tojal Silva; Severino S. Ferreira; Luiz Juliano; Pedro H. Vendramini; Monique Batista da Costa Lemos; Marcos N. Eberlin; Victor Piana Andrade

    Clinically meaningful molecular subtypes for classification of breast cancers have been established, however, initiation and progression of these subtypes remain poorly understood. The recent development of desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) facilitates the convergence of analytical chemistry and traditional pathology, allowing chemical profiling with minimal tissue

    更新日期:2020-03-16
  • Localized Metabolomic Gradients in Patient-Derived Xenograft Models of Glioblastoma.
    Cancer Res. (IF 8.378) Pub Date : 2019-11-25
    Elizabeth C Randall,Begoña G C Lopez,Sen Peng,Michael S Regan,Walid M Abdelmoula,Sankha S Basu,Sandro Santagata,Haejin Yoon,Marcia C Haigis,Jeffrey N Agar,Nhan L Tran,William F Elmquist,Forest M White,Jann N Sarkaria,Nathalie Y R Agar

    Glioblastoma (GBM) is increasingly recognized as a disease involving dysfunctional cellular metabolism. GBMs are known to be complex heterogeneous systems containing multiple distinct cell populations and are supported by an aberrant network of blood vessels. A better understanding of GBM metabolism, its variation with respect to the tumor microenvironment, and resulting regional changes in chemical

    更新日期:2020-03-16
  • Increased Tumor Penetration of Single-Domain Antibody Drug Conjugates Improves In Vivo Efficacy in Prostate Cancer Models.
    Cancer Res. (IF 8.378) Pub Date : 2020-01-15
    Ian Nessler,Eshita Khera,Steven Vance,Anna Kopp,Qifeng Qiu,Thomas A Keating,Adnan O Abu-Yousif,Thomas Sandal,James Legg,Lorraine Thompson,Normann Goodwin,Greg M Thurber

    Targeted delivery of chemotherapeutics aims to increase efficacy and lower toxicity by concentrating drugs at the site-of-action, a method embodied by the seven current FDA approved antibody-drug conjugates (ADCs). However, a variety of pharmacokinetic challenges result in relatively narrow therapeutic windows for these agents, hampering the development of new drugs. Here, we use a series of Prostate-Specific

    更新日期:2020-03-16
  • BACH1 promotes pancreatic cancer metastasis by repressing epithelial genes and enhancing epithelial-mesenchymal transition.
    Cancer Res. (IF 8.378) Pub Date : 2020-01-09
    Masaki Sato,Mitsuyo Matsumoto,Yuriko Saiki,Mahabub Alam,Hironari Nishizawa,Masahiro Rokugo,Andrey Brydun,Shinji Yamada,Mika K Kaneko,Ryo Funayama,Mamoru Ito,Yukinari Kato,Keiko Nakayama,Michiaki Unno,Kazuhiko Igarashi

    Pancreatic ductal adenocarcinoma (PDAC) is among the cancers with the poorest prognoses due to its highly malignant features. BTB and CNC homology 1 (BACH1) has been implicated in RAS-driven tumor formation. We focused on the role of BACH1 in PDAC, more than 90% of which have KRAS mutation. Knockdown of BACH1 in PDAC cell lines reduced cell migration and invasion in part by increasing E-cadherin expression

    更新日期:2020-03-16
  • The MEK5-ERK5 kinase axis controls lipid metabolism in small cell lung cancer.
    Cancer Res. (IF 8.378) Pub Date : 2020-01-22
    Sandra Cristea,Garry L Coles,Daniel Hornburg,Maya Gershkovitz,Julia Arand,Siqi Cao,Triparna Sen,Stuart Charles Williamson,Jun W Kim,Alexandros P Drainas,Andrew He,Laurent Le Cam,Lauren Averett Byers,Michael P Snyder,Kévin Contrepois,Julien Sage

    Small cell lung cancer (SCLC) is an aggressive form of lung cancer with dismal survival rates. While kinases often play key roles driving tumorigenesis, there are strikingly few kinases known to promote the development of SCLC. Here we investigated the contribution of the MAP kinase module MEK5/ERK5 to SCLC growth. MEK5 and ERK5 were required for optimal survival and expansion of SCLC cell lines in

    更新日期:2020-03-16
  • Activation of canonical BMP4-SMAD7 signaling suppresses breast cancer metastasis.
    Cancer Res. (IF 8.378) Pub Date : 2020-01-15
    Bedrich L Eckhardt,Yuan Cao,Andrew D Redfern,Lap Hing Chi,Allan D Burrows,Suraya Roslan,Erica K Sloan,Belinda S Parker,Sherene Loi,Naoto T Ueno,Peter K H Lau,Bruce Latham,Robin L Anderson

    Metastasis is the major cause of death in cancer patients; with no therapeutic cure, treatments remain largely palliative. As such, new targets and therapeutic strategies are urgently required. Here we show that bone morphogenetic protein-4 (BMP4) blocks metastasis in animal models of breast cancer and predicts improved survival in patients. In preclinical models of spontaneous metastasis, BMP4 acted

    更新日期:2020-03-16
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