Oncology

  • Article
    | Open Access

    Use of soluble boron compounds in prostate cancer therapy is hampered by their short half-life time and low effectiveness. Here, the authors show that boron nitride nanospheres with controlled boron release can reduce proliferation of prostate cancer cells and inhibit tumour growth in animal models.

    • Xia Li
    • , Xiupeng Wang
    •  & Dmitri Golberg
  • Article
    | Open Access

    Radiotherapy can enhance the antitumour immune response. Here, the authors show that resistance to radiation in breast cancer cells can be due to Axl expression that suppresses antigen presentation though MHCI, promotes NF-κB signalling, and enhances cytokine release promoting a suppressive myeloid microenvironment.

    • Todd A. Aguilera
    • , Marjan Rafat
    •  & Amato J. Giaccia
  • Article
    | Open Access

    Polypeptide N-acetyl-galactosaminyltransferases (GALNTs) are associated with cancer, but their function in organ-specific metastasis is unclear. Here the authors show that GALNT14 promotes breast cancer metastasis to the lung by enhancing the initiation of metastatic colonies and subsequent growth.

    • Ki-Hoon Song
    • , Mi So Park
    •  & Mi-Young Kim
  • Article
    | Open Access

    Some colorectal cancer patients respond well to treatment with anti-EGFR antibodies, however response is almost invariably followed by acquired resistance. Here, the authors show that patients with shorter responses acquireRAS mutations, while those relapsing later preferentially develop mutations in the extracellular domain of EGFR.

    • Beth O. Van Emburgh
    • , Sabrina Arena
    •  & Alberto Bardelli
  • Article
    | Open Access

    Cytoplasmic polyadenylated transcripts have been poorly characterized, particularly in cancer. Here the authors identify a lineage-specific requirement of the cytoplasmic polyadenylation binding protein 4 (CPEB4) in malignant melanoma and show that it controls melanoma drivers MITF and RAB27A.

    • Eva Pérez-Guijarro
    • , Panagiotis Karras
    •  & María S. Soengas
  • Article
    | Open Access

    Activation and biological function of B cells in cancer are still unclear. Here, the authors show that hepatocarcinoma cells drive the formation of semimature dendritic cells that in turn activate FcγRIIlow/−tumour B cells through the CD95L/CD95 axis, leading to the production of IL-10 and suppression of CD8 T cells.

    • Fang-Zhu Ouyang
    • , Rui-Qi Wu
    •  & Dong-Ming Kuang
  • Article
    | Open Access

    Determining the most effective treatment for each cancer patient is a key challenge in cancer therapy. In this article, the authors show, in a mouse model of breast cancer, that DNA barcoded nanoparticles can be used for pre-screening the efficacy of anticancer drugs.

    • Zvi Yaari
    • , Dana da Silva
    •  & Avi Schroeder
  • Article
    | Open Access

    Aromatase inhibitors are used to treat oestrogen receptor positive breast cancers but the molecular basis for the response of patients is unclear. Here, the authors use samples from an aromatase inhibitor clinical trial and show that tumours from poor responders have more mutations than good responders and also more frequently harbour p53 mutations.

    • Pascal Gellert
    • , Corrinne V. Segal
    •  & Peter Donnelly
  • Article
    | Open Access

    Dysregulation of protein degradation by the ubiquitin-proteasome system is a feature commonly associated with cancer. Here, the authors develop an orally available small molecule that inhibits CSN5, the proteolytic subunit of the COP9 signalosome, and blocks tumour growth in a xenograft model.

    • Anita Schlierf
    • , Eva Altmann
    •  & Bruno Martoglio
  • Article
    | Open Access

    The polycomb repressor protein Bmi1 has a role in self-renewal and tumorigenesis. Here, the authors use lineage tracing to show that Bmi-expressing cells are a distinct population of cells, primarily found in the luminal compartment, which is castration resistant, can initiate cancer and regenerate prostate.

    • Young A. Yoo
    • , Meejeon Roh
    •  & Sarki A. Abdulkadir
  • Article
    | Open Access

    Drugs that sensitize tumour cells to ionizing radiation are prized because they can overcome resistance to radiotherapy. Here, the authors show that anti-tubulin drugs conjugated to cetuximab or trastuzumab can radiosensitize EGFR- or HER2-expressing tumors by increasing DNA damage and cell death due to ionizing radiation.

    • Stephen R. Adams
    • , Howard C. Yang
    •  & Sunil J. Advani
  • Article
    | Open Access

    Pre-leukaemic clones, together with the propensity to cause disease in mice, are characterized by appearing early in myeloid leukaemia and being found at relapse. Here, the authors identify clones in human samples and find that they are characterized by hierarchically organized genetic lesions, which can be used to track evolution of the disease.

    • Pierre Hirsch
    • , Yanyan Zhang
    •  & François Delhommeau
  • Article
    | Open Access

    The PARP inhibitor olaparib is an approved treatment method for women with BRCA1 and BRCA2 mutation associated cancers. Here the authors show that olaparib can contribute to synthetic viability of cells if PARP1 is inhibited before BRCA2 loss.

    • Xia Ding
    • , Arnab Ray Chaudhuri
    •  & Shyam K. Sharan
  • Article
    | Open Access

    Noscapine is a potential anticancer drug that is traditionally isolated from the opium poppy Papaver somniferum. Here, Li and Smolke reconstitute the noscapine gene cluster in Saccharomyces cerevisiae, to achieve the microbial production of noscapine and related pathway intermediates, and provide new insights into the biosynthesis of noscapine.

    • Yanran Li
    •  & Christina D. Smolke
  • Article
    | Open Access

    Phenotypic and genetic intra-tumor heterogeneity have an important role in cancer progression and therapeutic resistance. Here, the authors show that phenotypically variable tumor subpopulations exhibit higher metastatic potential and display enhanced intra-clonal transcriptomic variability, likely promoted by deregulated spliceosome activity.

    • Alexander Nguyen
    • , Mitsukuni Yoshida
    •  & Sohail F. Tavazoie
  • Article
    | Open Access

    Oesophageal adenocarcinoma is often treated with chemotherapy before surgery. Here, the authors sequence cancer samples before and after chemotherapy and examine how the genome changes, focusing on changes in driver gene mutations and differential clonal evolution between good and poor responders.

    • John M. Findlay
    • , Francesc Castro-Giner
    •  & Ian Tomlinson
  • Article
    | Open Access

    The formation of blood vessels in tumours, angiogenesis, is a promising target for therapy. Here, the authors show that microRNA192 has anti-angiogenic functions and negatively regulates EGR1 and HOXB9, and that delivery of this microRNA to tumours in vivocan reduce angiogenesis and tumour growth.

    • Sherry Y. Wu
    • , Rajesha Rupaimoole
    •  & Anil K. Sood
  • Article
    | Open Access

    Merlin plays a crucial role as a tumour suppressor in liver tumorigenesis. Here, the authors show that a splicing variant of Merlin that lacks exons 2,3 and 4 (Δ2–4Merlin) is highly expressed in hepatocarcinoma and promotes tumour metastasis by interfering with the binding of wild-type Merlin to ß-catenin.

    • Zai-Li Luo
    • , Shu-Qun Cheng
    •  & Zhong Li
  • Article
    | Open Access

    With no cell lines available, investigating the aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs) has proved problematic. Here, Oikawa et al. establish a model of hFL-HCCs as a transplantable tumour line maintained in immune-compromised mice, which proves rich in cancer stem cells.

    • Tsunekazu Oikawa
    • , Eliane Wauthier
    •  & Lola M. Reid
  • Article
    | Open Access

    Chemokines and their receptors have key roles in tumorigenesis. Here, the authors demonstrate that CXRC4 is overexpressed in hepatocellular carcinoma and is associated with poor prognosis and, mechanistically CXCR4 is increased in expression via EZH2 repression of microRNA-622.

    • Haiou Liu
    • , Yidong Liu
    •  & Jiejie Xu
  • Article
    | Open Access

    Tumour cells can survive by evading cell death pathways and altering their metabolism to adapt to their local environment. In this study, Iansanteet al. show that the anti-apoptotic protein PARP14 maintains low PKM2 activity, leading to enhanced glycolysis, demonstrating a link between suppression of apoptosis and altered metabolism.

    • Valeria Iansante
    • , Pui Man Choy
    •  & Salvatore Papa
  • Article
    | Open Access

    The EphA2 receptor tyrosine kinase is overexpressed in many cancers and is reported to be phosphorylated by Akt. Here, Zhou et al.show that RSK, rather than Akt, phosphorylates EphA2 on Ser-897, and this regulates cell migration and invasion of metastatic cancer cells.

    • Yue Zhou
    • , Naoki Yamada
    •  & Hiroaki Sakurai
  • Article |

    Chronic myeloid leukaemia is characterized by the genetic translocation t(9;22) encoding for BCR-ABL oncogene; however, the molecular mechanisms of disease progression are poorly understood. Here Amabile et al. show that aberrant methylation is promoted by BCR-ABL, driving the evolution of the disease.

    • Giovanni Amabile
    • , Annalisa Di Ruscio
    •  & Daniel G. Tenen
  • Article |

    Some normal and cancer stem cells are resistant to killing by genotoxins, but the mechanism for this resistance is poorly understood. Here the authors show that adult stem cells inDrosophila melanogastergermline and midgut are resistant to genotoxic stimuli and find that this is mediated by signalling via the receptor tyrosine kinase Tie released from apoptotic cells.

    • Yalan Xing
    • , Tin Tin Su
    •  & Hannele Ruohola-Baker
  • Article
    | Open Access

    Folate plays an essential role in dividing cells and is regulated by methionine adenosyltransferase (MAT), where a switch from MAT Iα to MAT IIα expression seems to promote liver cancer progression. Here the authors demonstrate that MAT IIα stability is regulated by acetylation and this regulation is important for tumour growth.

    • Hong-Bin Yang
    • , Ying-Ying Xu
    •  & Qun-Ying Lei
  • Article |

    In mammals there are two Musashi proteins, MSI1 and MSI2, orthologues of the Drosophila protein, with roles in asymmetric stem cell division and cell fate determination. Here the authors report new functions for MSI2 in colorectal cancer using in vitro loss of function and in vivoectopic overexpression.

    • Shan Wang
    • , Ning Li
    •  & Christopher J. Lengner