Browse Articles

  • Article |

    TGF-β induces expression of ADAM10, which results in greater shedding of ephrin-B2. This shedding promotes the chemotaxis and activation of myofibroblasts and thus the progression of organ fibrosis.

    • David Lagares
    • , Parisa Ghassemi-Kakroodi
    • , Caroline Tremblay
    • , Alba Santos
    • , Clemens K Probst
    • , Alicia Franklin
    • , Daniela M Santos
    • , Paula Grasberger
    • , Neil Ahluwalia
    • , Sydney B Montesi
    • , Barry S Shea
    • , Katharine E Black
    • , Rachel Knipe
    • , Meryem Blati
    • , Murray Baron
    • , Brian Wu
    • , Hassan Fahmi
    • , Rajiv Gandhi
    • , Annie Pardo
    • , Moisés Selman
    • , Jiangping Wu
    • , Jean-Pierre Pelletier
    • , Johanne Martel-Pelletier
    • , Andrew M Tager
    •  & Mohit Kapoor
  • Article |

    Concomitant overexpression of microRNAs miR-100 and miR-125b-1 within the host long non-coding RNA MIR100HG induces cetuximab resistance in cancer in the absence of previously associated genetic alterations. miR-100 and miR-125b target negative regulators of Wnt/β-catenin signaling and sustain drug resistance through feedback inhibition of GATA6 expression and this resistance can be overcome by pharmacological inhibition of Wnt activity. These findings, together with those by Tan et al. in the previous issue, highlight the emerging functional role of non-coding RNAs in modulating the response to anti-cancer therapies.

    • Yuanyuan Lu
    • , Xiaodi Zhao
    • , Qi Liu
    • , Cunxi Li
    • , Ramona Graves-Deal
    • , Zheng Cao
    • , Bhuminder Singh
    • , Jeffrey L Franklin
    • , Jing Wang
    • , Huaying Hu
    • , Tianying Wei
    • , Mingli Yang
    • , Timothy J Yeatman
    • , Ethan Lee
    • , Kenyi Saito-Diaz
    • , Scott Hinger
    • , James G Patton
    • , Christine H Chung
    • , Stephan Emmrich
    • , Jan-Henning Klusmann
    • , Daiming Fan
    •  & Robert J Coffey
  • Letter |

    In rodent models of Alzheimer's disease (AD) and epilepsy, seizure-dependent induction of ΔFosB results in epigenetic silencing of calbindin. Hippocampal inhibition of ΔFosB or elevation of calbindin rescues spatial memory deficits in mouse models of AD.

    • Jason C You
    • , Kavitha Muralidharan
    • , Jin W Park
    • , Iraklis Petrof
    • , Mark S Pyfer
    • , Brian F Corbett
    • , John J LaFrancois
    • , Yi Zheng
    • , Xiaohong Zhang
    • , Carrie A Mohila
    • , Daniel Yoshor
    • , Robert A Rissman
    • , Eric J Nestler
    • , Helen E Scharfman
    •  & Jeannie Chin
  • Article |

    Huot et al. investigate the differences in natural killer (NK) cells in lymph nodes during pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infection of cynomolgus macaques and African green monkeys (AGMs), respectively. Their findings suggest that NK cells are specifically recruited to follicles in AGMs and regulate SIV replication in the lymph node.

    • Nicolas Huot
    • , Beatrice Jacquelin
    • , Thalia Garcia-Tellez
    • , Philippe Rascle
    • , Mickaël J Ploquin
    • , Yoann Madec
    • , R Keith Reeves
    • , Nathalie Derreudre-Bosquet
    •  & Michaela Müller-Trutwin
  • Article |

    Combined inhibition of oncogene-driven glucose uptake and induction of cytoplasmic-p53 activity induces apoptosis in a subset of glioblastoma samples. In mice, PET imaging of glucose uptake predicts glioblastoma response to this combination therapy.

    • Wilson X Mai
    • , Laura Gosa
    • , Veerle W Daniels
    • , Lisa Ta
    • , Jonathan E Tsang
    • , Brian Higgins
    • , W Blake Gilmore
    • , Nicholas A Bayley
    • , Mitra Dehghan Harati
    • , Jason T Lee
    • , William H Yong
    • , Harley I Kornblum
    • , Steven J Bensinger
    • , Paul S Mischel
    • , P Nagesh Rao
    • , Peter M Clark
    • , Timothy F Cloughesy
    • , Anthony Letai
    •  & David A Nathanson
  • Article |

    Sympathetic neuron–associated macrophages act as a local sink for norepinephrine, leading to reduced thermogenesis and increased obesity.

    • Roksana M Pirzgalska
    • , Elsa Seixas
    • , Jason S Seidman
    • , Verena M Link
    • , Noelia Martínez Sánchez
    • , Inês Mahú
    • , Raquel Mendes
    • , Vitka Gres
    • , Nadiya Kubasova
    • , Imogen Morris
    • , Bernardo A Arús
    • , Chelsea M Larabee
    • , Miguel Vasques
    • , Francisco Tortosa
    • , Ana L Sousa
    • , Sathyavathy Anandan
    • , Erin Tranfield
    • , Maureen K Hahn
    • , Matteo Iannacone
    • , Nathanael J Spann
    • , Christopher K Glass
    •  & Ana I Domingos
  • Article |

    Microenvironmental pressures in glioblastoma select for glioma stem cells (GSCs) subpopulations that are maintained through preferential activation of BMI1 and EZH2 in different niches. Given the high degree of intratumor heterogeneity, combined pharmacological inhibition of Polycomb repressive complexes targets proneural and mesenchynmal GSCs and expands lifespan in mice, warranting the therapeutic evaluation of this approach in patients with glioblastoma.

    • Xun Jin
    • , Leo J Y Kim
    • , Qiulian Wu
    • , Lisa C Wallace
    • , Briana C Prager
    • , Tanwarat Sanvoranart
    • , Ryan C Gimple
    • , Xiuxing Wang
    • , Stephen C Mack
    • , Tyler E Miller
    • , Ping Huang
    • , Claudia L Valentim
    • , Qi-gang Zhou
    • , Jill S Barnholtz-Sloan
    • , Shideng Bao
    • , Andrew E Sloan
    •  & Jeremy N Rich
  • Article |

    Hiroyuki Arai and colleagues characterize a new group of epoxy ω-3 fatty acid–derived proinflammatory lipid mediators, an enzyme mediating their biosynthesis and a signaling pathway by which they regulate a threshold of mast cell activation and anaphylaxis, revealing new targets for mast cell–mediated diseases.

    • Yuta Shimanaka
    • , Nozomu Kono
    • , Yoshitaka Taketomi
    • , Makoto Arita
    • , Yoshimichi Okayama
    • , Yuki Tanaka
    • , Yasumasa Nishito
    • , Tatsuki Mochizuki
    • , Hiroyuki Kusuhara
    • , Alexander Adibekian
    • , Benjamin F Cravatt
    • , Makoto Murakami
    •  & Hiroyuki Arai
  • Article |

    Obesity induces hypoxia and upregulation of HIF-2α in the gastrointestinal tract, resulting in excess ceramide production and exacerbation of NAFLD.

    • Cen Xie
    • , Tomoki Yagai
    • , Yuhong Luo
    • , Xianyi Liang
    • , Tao Chen
    • , Qiong Wang
    • , Dongxue Sun
    • , Jie Zhao
    • , Sadeesh K Ramakrishnan
    • , Lulu Sun
    • , Chunmei Jiang
    • , Xiang Xue
    • , Yuan Tian
    • , Kristopher W Krausz
    • , Andrew D Patterson
    • , Yatrik M Shah
    • , Yue Wu
    • , Changtao Jiang
    •  & Frank J Gonzalez
  • Review |

    In this Review, Ferrando and López-Otín discuss the role of clonal evolution in leukemia and propose that better understanding of the evolutionary biography of human leukemias and related blood cell malignancies may contribute to improve their clinical management.

    • Adolfo A Ferrando
    •  & Carlos López-Otín
  • News and Views |

    Three recent studies in mice have identified a specific receptor, GFRAL, for the known anorectic peptide GDF15. The finding increases mechanistic understanding of its effect and paves the way for the development of novel anti-obesity therapeutics.

    • Irene Cimino
    • , Anthony P Coll
    •  & Giles S H Yeo
  • Editorial |

    A growing number of clinical trials on combination therapies raises the question of to what degree they may be redundant. Systems biology and hypothesis-driven preclinical studies could help to identify the most promising candidates for clinical trials, and also offer new insights into the biological mechanisms that underlie drug synergies.

  • Erratum |

    • Daniel A Giles
    • , Maria E Moreno-Fernandez
    • , Traci E Stankiewicz
    • , Simon Graspeuntner
    • , Monica Cappelletti
    • , David Wu
    • , Rajib Mukherjee
    • , Calvin C Chan
    • , Matthew J Lawson
    • , Jared Klarquist
    • , Annika Sünderhauf
    • , Samir Softic
    • , C Ronald Kahn
    • , Kerstin Stemmer
    • , Yoichiro Iwakura
    • , Bruce J Aronow
    • , Rebekah Karns
    • , Kris A Steinbrecher
    • , Christopher L Karp
    • , Rachel Sheridan
    • , Shiva K Shanmukhappa
    • , Damien Reynaud
    • , David B Haslam
    • , Christian Sina
    • , Jan Rupp
    • , Simon P Hogan
    •  & Senad Divanovic
  • News and Views |

    A new mouse model of Rett syndrome, in which MECP2 can be selectively biotinylated, allows for the investigation of cell-specific effects of Rett-causing mutations on gene expression, particularly in female mice.

    • Patricia M Horvath
    •  & Lisa M Monteggia
  • Letter |

    Frequent loss-of-function mutations in KEAP1, a master regulator of the NRF2 antioxidant pathway, accelerate mutant KRAS driven lung carcinogenesis, but also impose a dependency of these tumors on glutaminolysis. Using a precision medicine–based approach, this work uncovers a metabolic vulnerability of KRASKEAP1-mutant lung cancers that can be therapeutically exploited using currently available glutaminase inhibitors and provides a scientific rationale for patient selection in clinical trials.

    • Rodrigo Romero
    • , Volkan I Sayin
    • , Shawn M Davidson
    • , Matthew R Bauer
    • , Simranjit X Singh
    • , Sarah E LeBoeuf
    • , Triantafyllia R Karakousi
    • , Donald C Ellis
    • , Arjun Bhutkar
    • , Francisco J Sánchez-Rivera
    • , Lakshmipriya Subbaraj
    • , Britney Martinez
    • , Roderick T Bronson
    • , Justin R Prigge
    • , Edward E Schmidt
    • , Craig J Thomas
    • , Chandra Goparaju
    • , Angela Davies
    • , Igor Dolgalev
    • , Adriana Heguy
    • , Viola Allaj
    • , John T Poirier
    • , Andre L Moreira
    • , Charles M Rudin
    • , Harvey I Pass
    • , Matthew G Vander Heiden
    • , Tyler Jacks
    •  & Thales Papagiannakopoulos
  • Article |

    Quantifying the total-body virus burden in HIV-infected individuals is necessary to understand viral persistence and guide development of cure strategies. Here, Estes et al. find a high burden of residual virus in tissues of SIV-infected monkeys and HIV-infected humans, and evidence of low-level viral replication, even under antiretroviral therapy.

    • Jacob D Estes
    • , Cissy Kityo
    • , Francis Ssali
    • , Louise Swainson
    • , Krystelle Nganou Makamdop
    • , Gregory Q Del Prete
    • , Steven G Deeks
    • , Paul A Luciw
    • , Jeffrey G Chipman
    • , Gregory J Beilman
    • , Torfi Hoskuldsson
    • , Alexander Khoruts
    • , Jodi Anderson
    • , Claire Deleage
    • , Jacob Jasurda
    • , Thomas E Schmidt
    • , Michael Hafertepe
    • , Samuel P Callisto
    • , Hope Pearson
    • , Thomas Reimann
    • , Jared Schuster
    • , Jordan Schoephoerster
    • , Peter Southern
    • , Katherine Perkey
    • , Liang Shang
    • , Stephen W Wietgrefe
    • , Courtney V Fletcher
    • , Jeffrey D Lifson
    • , Daniel C Douek
    • , Joseph M McCune
    • , Ashley T Haase
    •  & Timothy W Schacker
  • Article |

    Amplification of chromosome 1q21.3 distinguishes cells with tumor-initiating capacity that drive tumor recurrence across different breast cancer subtypes. A droplet digital PCR assay in circulating free tumor DNA identifies patients with early-stage cancer at high risk of relapse and predicts response to therapy in the metastatic setting. Pharmacological blockade of targets within this amplicon using a clinically available compound prevents tumor recurrence, suggesting a potential therapeutic approach to improve the clinical management of patients harboring 1q21.3-amplified breast tumors.

    • Jian Yuan Goh
    • , Min Feng
    • , Wenyu Wang
    • , Gokce Oguz
    • , Siti Maryam J M Yatim
    • , Puay Leng Lee
    • , Yi Bao
    • , Tse Hui Lim
    • , Panpan Wang
    • , Wai Leong Tam
    • , Annette R Kodahl
    • , Maria B Lyng
    • , Suman Sarma
    • , Selena Y Lin
    • , Alexander Lezhava
    • , Yoon Sim Yap
    • , Alvin S T Lim
    • , Dave S B Hoon
    • , Henrik J Ditzel
    • , Soo Chin Lee
    • , Ern Yu Tan
    •  & Qiang Yu
  • Letter |

    The N6-methyladenosine (m6A) modification in mRNAs, generated by the enzyme METTL3, controls normal human hematopoietic stem/progenitor cell differentiation and maintains the undifferentiated leukemic phenotype of human acute myeloid leukemia cells.

    • Ly P Vu
    • , Brian F Pickering
    • , Yuanming Cheng
    • , Sara Zaccara
    • , Diu Nguyen
    • , Gerard Minuesa
    • , Timothy Chou
    • , Arthur Chow
    • , Yogesh Saletore
    • , Matthew MacKay
    • , Jessica Schulman
    • , Christopher Famulare
    • , Minal Patel
    • , Virginia M Klimek
    • , Francine E Garrett-Bakelman
    • , Ari Melnick
    • , Martin Carroll
    • , Christopher E Mason
    • , Samie R Jaffrey
    •  & Michael G Kharas