Featured
-
-
Article
| Open AccessPotent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells
Interleukin-2 (IL-2) is a T-cell proliferating factor used for cancer immunotherapy. Here, the authors develop a long-lived variant of IL-2 that, mutated in its binding domain, drives a much more potent tumour regression by depleting CD25+ CD4+regulatory T-cells via targeting them for phagocytosis.
- Rodrigo Vazquez-Lombardi
- , Claudia Loetsch
- & Daniel Christ
-
Article
| Open AccessRAF proteins exert both specific and compensatory functions during tumour progression of NRAS-driven melanoma
The melanoma-driver mutations in NRAS and BRAF are mutually exclusive but the contribution of RAF signalling downstream of NRAS remains to be clarified. Here, using mouse models, the authors show specific roles of each member of the RAF family at different stages of melanomagenesis.
- Coralie Dorard
- , Charlène Estrada
- & Sabine Druillennec
-
Article
| Open AccessImage-guided genomics of phenotypically heterogeneous populations reveals vascular signalling during symbiotic collective cancer invasion
The mechanisms linking phenotypic heterogeneity to collective cancer invasion are unclear. Here the authors develop an image-guided genomic technique to select and amplify leader and follower cells fromin vitroinvading cell packs and find a cooperative symbiotic relationship between these two cell populations.
- J. Konen
- , E. Summerbell
- & A. I. Marcus
-
Article
| Open AccessPTEN regulates glioblastoma oncogenesis through chromatin-associated complexes of DAXX and histone H3.3
PTEN mutations are frequent in glioblastoma and often are associated with therapeutic resistance. Here, the authors demonstrate that PTEN regulates gene expression at the chromatin level by interacting with the histone chaperone DAXX and H3.3, and that DAXX inhibition inhibits PTEN-deficient GBM growth in vivo.
- Jorge A. Benitez
- , Jianhui Ma
- & Frank B. Furnari
-
Article
| Open AccessProline metabolism supports metastasis formation and could be inhibited to selectively target metastasizing cancer cells
Metastasizing cancer cells rewire their metabolism to support their malignant phenotypes. Here, the authors show that the acquisition of a metastatic phenotype in breast cancer cell lines results in increased proline catabolism and that inhibition of this pathway decreases lung metastasis formation in two mouse models.
- Ilaria Elia
- , Dorien Broekaert
- & Sarah-Maria Fendt
-
Article
| Open AccessCirculating tumour DNA sequence analysis as an alternative to multiple myeloma bone marrow aspirates
Genetic profiling of multiple myeloma requires painful bone marrow biopsies. Here, the authors develop an alternative non-invasive method for sequencing of five oncogenes in circulating cell-free DNA from myeloma patients, demonstrating 96% concordance with bone marrow tumour profiling results.
- Olena Kis
- , Rayan Kaedbey
- & Trevor J. Pugh
-
Article
| Open AccessProlonged intracellular accumulation of light-inducible nanoparticles in leukemia cells allows their remote activation
Leukaemia cells resident in the bone marrow niche are often resistant to conventional therapies. In this study, the authors develop light-sensitive, polymeric, retinoic acid-containing nanoparticles that are able to modulate the differentiation of resistant leukaemia cells bothin vitro and in vivo.
- Carlos Boto
- , Emanuel Quartin
- & Lino Ferreira
-
Article
| Open AccessImaging of pH in vivo using hyperpolarized 13C-labelled zymonic acid
Local pH alterations can be manifestations of pathologies such as cancer, inflammation and ischaemia. Here Düwelet al. show hyperpolarized 13C-labelled zymonic acid can be used as a non-invasive probe to map and measure pH in vivo, suggesting it as a candidate for clinical imaging and a diagnostic tool.
- Stephan Düwel
- , Christian Hundshammer
- & Franz Schilling
-
Article
| Open AccessSenescent tumor cells lead the collective invasion in thyroid cancer
The senescence-associated secretory phenotype of stromal cells can promote tumorigenesis. Here, the authors show that senescent cancer cells are localized at the invasive front in human papillary thyroid carcinoma, and that senescent cancer cells drive collective invasion via CXCL12 in mouse models.
- Young Hwa Kim
- , Yong Won Choi
- & Tae Jun Park
-
Article
| Open AccessBlockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-γ-induced immunologic dormancy of tumor-repopulating cells
Tumour repopulating cells (TRC) are stem-like cells that can escape immune-mediated killing. Here, the authors show IFN-γ results in either dormancy or apoptosis of TRC depending on the activation of the IDO1 metabolic pathway, and that combining IFN-γ with IDO1 inhibitors results in enhanced tumour regression.
- Yuying Liu
- , Xiaoyu Liang
- & Bo Huang
-
Article
| Open AccessAntibody targeting intracellular oncogenic Ras mutants exerts anti-tumour effects after systemic administration
Oncogenic RAS mutants are key anti-cancer targets as KRas mutations are very frequent in human cancers. Here, the authors engineer a cytosol-penetrating anti-Ras antibody and demonstrate its ability to block RAS-effector protein interactions inhibiting tumour growth of Ras mutant-driven cancers.
- Seung-Min Shin
- , Dong-Ki Choi
- & Yong-Sung Kim
-
Article
| Open AccessAnalysis of renal cancer cell lines from two major resources enables genomics-guided cell line selection
Cell lines are central to cancer research, but knowing which cell lines are the best representative of actual tumours is a major challenge. Here the authors provide a resource assessment of 65 renal cell lines to assist researchers in selecting suitable lines for studying specific renal carcinoma subtypes.
- Rileen Sinha
- , Andrew G. Winer
- & A. Ari Hakimi
-
Article
| Open AccessLipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis
Drug delivery in brain tumours is still a significant clinical concern. In this study, the authors develop a biomimetic lipoprotein nanoparticle for the efficient delivery of ATF5 siRNA inRas-activated brain cancer cells, where the nanoparticle is internalized by macropinocytosis in a Ras-dependent manner.
- Jia-Lin Huang
- , Gan Jiang
- & Xiao-Ling Gao
-
Article
| Open AccessSingle-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer
Genetic heterogeneity in breast cancer has been demonstrated at a single-cell resolution with high levels of genome coverage. Here, the authors perform transcriptome analysis of 515 single cells from 11 patients and define core gene expression signatures for subtype-specific single breast cancer cells and tumour-infiltrating immune cells.
- Woosung Chung
- , Hye Hyeon Eum
- & Woong-Yang Park
-
Article
| Open AccessStat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1
Cancer cells have amplified centrosomes and deal with this abnormality by clustering them together so that they can be segregated in daughter cells. Here the authors perform a screening looking for inhibitors of this clustering process and find that STAT3 regulates this process independently of its transcriptional function.
- Edward J. Morris
- , Eiko Kawamura
- & Shoukat Dedhar
-
Article
| Open AccessThe essential role of YAP O-GlcNAcylation in high-glucose-stimulated liver tumorigenesis
Yap is a transcriptional factor involved in tumorigenesis. Here the authors show that a previously unknown post-translational modification of Yap, O-GlcNAcylation, increases its transcriptional activity and is required for high glucose-induced liver cancer development.
- Xiao Zhang
- , Yongxia Qiao
- & Fenyong Sun
-
Article
| Open AccessMenin enhances c-Myc-mediated transcription to promote cancer progression
Menin is a protein with context-dependent oncogenic or oncosuppressive roles; the oncogenic activity is mainly due to its function as a cofactor of the MLL1 histone methyltransferase complex. Here the authors show that Menin regulates c-Myc-dependent transformation independently of the MLL complex.
- Gongwei Wu
- , Mengqiu Yuan
- & Ping Gao
-
Article
| Open AccessComprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2
Lynch syndrome is characterized by predisposition to colorectal cancer and mutations in genes involved in mismatch repair. Here, the authors use whole genome sequencing and immunohistochemistry of mismatch repair proteins to show a high prevalence of Lynch syndrome in the Icelandic population.
- Sigurdis Haraldsdottir
- , Thorunn Rafnar
- & Kari Stefansson
-
Article
| Open AccessHMGA1 amplifies Wnt signalling and expands the intestinal stem cell compartment and Paneth cell niche
The function of high mobility group A1 (Hmga1) chromatin remodelling proteins in intestinal stem cells (ISC) is unknown. Here, the authors show that Hmga1 amplifies Wnt/β-catenin signalling to enhance self-renewal and inducesSox9to expand the Paneth cell compartment and enrich the ISC niche.
- Lingling Xian
- , Dan Georgess
- & Linda M. S. Resar
-
Article
| Open AccessFunctional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148
Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.
- Jun Fang
- , Jinping Jia
- & Laufey T. Amundadottir
-
Article
| Open AccessSpatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer
The functional significance of T-cell infiltration in pancreatic ductal adenocarcinoma in relation to desmoplastic stroma is unclear. Here the authors develop a method to spatially resolve tumour stroma composition and find that spatial T-cell infiltration correlates with patient prognosis regardless of desmoplasia.
- Julienne L. Carstens
- , Pedro Correa de Sampaio
- & Raghu Kalluri
-
Article
| Open AccessPARP3 is a promoter of chromosomal rearrangements and limits G4 DNA
Chromosomal rearrangements are key events in the pathogenesis of a range of disorders. Here the authors utilize a zinc finger nuclease translocation reporter to identify PARP3 as a regulator of these events at sites enriched for G quadruplex DNA.
- Tovah A. Day
- , Jacob V. Layer
- & David M. Weinstock
-
Article
| Open AccessFAF1 phosphorylation by AKT accumulates TGF-β type II receptor and drives breast cancer metastasis
Aberrant activation of TGF-β signalling promotes cancer metastasis but the initial steps of this activation are unclear. Here Xieet al. show that FAF1 regulates the surface levels of TGF-β type II receptor thus influencing the persistence of the signalling and breast cancer metastasis.
- Feng Xie
- , Ke Jin
- & Long Zhang
-
Article
| Open AccessGold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer
Nerve growth factor (NGF) contributes to the sustained growth and metastasis of pancreatic cancer cells. Here, the authors develop a gold nanocluster-coupled siRNA against NGF that efficiently silences theNGFgene and inhibits tumour growth of pancreatic cancer in mice.
- Yifeng Lei
- , Lixue Tang
- & Xingyu Jiang
-
Article
| Open AccessKDM3 epigenetically controls tumorigenic potentials of human colorectal cancer stem cells through Wnt/β-catenin signalling
Epigenetic factors can regulate functional properties of human colorectal cancer stem cells. Here, the authors show that histone demethylases of the KDM3 family activate Wnt signalling in colorectal cancer stem cells by erasing H3K9me2 marks on Wnt target genes and recruiting MLL1 to promote H3K4 methylation.
- Jiong Li
- , Bo Yu
- & Cun-Yu Wang
-
Article
| Open AccessTet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells
TET2 catalyses DNA demethylation and is mutated in various blood cancers; in particularTet2null mice develop haematological neoplasms. Here the authors show that this effect could be due to the increased frequency of mutation associated with TET2 loss in haematopoietic stem/progenitor cells.
- Feng Pan
- , Thomas S. Wingo
- & Mingjiang Xu
-
Article
| Open AccessLPP is a Src substrate required for invadopodia formation and efficient breast cancer lung metastasis
Lipoma preferred partner (LPP) mediates TGFβ-induced breast cancer cell migration and invasion. Here the authors show that LPP is a Src-family kinase substrate that regulates the formation of protrusions of the plasma membrane -called invadopodia- required for breast cancer metastasis.
- Elaine Ngan
- , Konstantin Stoletov
- & Peter M. Siegel
-
Article
| Open AccessBone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies
The bone microenvironment may alter therapeutic responses of disseminated breast cancer cells. Here the authors establish anex vivobone metastasis model, termed BICA, to delineate the effects of bone microenvironment and to rapidly discover anti-metastasis drugs.
- Hai Wang
- , Lin Tian
- & Xiang H.-F. Zhang
-
Article
| Open AccessPhylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations
Tumour heterogeneity is well-known; however, studies analysing the progression from primary to metastatic disease are still limited. Here, the authors used phylogenetic analyses and found that for some patients there are multiple seeding events from the primary tumour accompanied by cross-seeding between metastases.
- David Brown
- , Dominiek Smeets
- & Christine Desmedt
-
Article
| Open AccessClonal evolution in myelodysplastic syndromes
Myelodysplastic syndromes are a broad group of haematopoietic malignancies that often progress to acute myeloid leukaemia. Here, the authors show that linear and branched evolution occurs within myelodysplastic syndrome and these patterns can be impacted by treatment.
- Pedro da Silva-Coelho
- , Leonie I. Kroeze
- & Joop H. Jansen
-
Article
| Open AccessUnification of de novo and acquired ibrutinib resistance in mantle cell lymphoma
Ibrutinib has demonstrated high response rates in B-cell lymphomas but a lot of ibrutinib-treated patients relapse with resistance. This study unified TME-mediatedde novoand acquired drug resistance through B-cell receptor signalling and PI3K-AKT-mTOR axis and provides a combination therapeutic strategy against B-cell malignancies.
- Xiaohong Zhao
- , Tint Lwin
- & Jianguo Tao
-
Article
| Open AccessLysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface
Lysyl oxidase is able to remodel the extracellular matrix and its expression correlates with poor prognosis. Here the authors show that this protein modulates trapping of the epidermal growth factor receptor at the cell surface, causing persistent signalling activation and tumour progression.
- HaoRan Tang
- , Leo Leung
- & Richard Marais
-
Article
| Open AccessPapilloma-pseudovirus eradicates intestinal tumours and triples the lifespan of ApcMin/+ mice
Innate immunity sensors are expressed by both tumour cells and tumour-associated myeloid cells. Here, the authors show that stimulation of the innate immunity response with pseudoviruses in a genetic mouse model of intestinal cancer triggers tumour regression via Caspase-1 activation.
- Zhenyu Zhong
- , Yougang Zhai
- & Liang Qiao
-
Article
| Open AccessComputational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer
Dysregulation of microRNAs is thought to be important for metastasis in castration-resistant prostate cancer (CRPC), but its drivers are unknown. Here, the authors use computational analysis to identify HOXC6 and NKX2-2 in addition to AR as alternative drivers of dysregulated miRNA expression in CRPC.
- Mengzhu Xue
- , Haiyue Liu
- & Peng Wang
-
Article
| Open AccessExosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis
EGFR signalling has been linked to cancer development but whether it has any role in pre-metastatic niche formation is not known. Here the authors show that gastric cancer cells send EGFR through exosomes to the liver where it causes the establishment of a favourable microenvironment thus promoting metastasis.
- Haiyang Zhang
- , Ting Deng
- & Yi Ba
-
Article
| Open AccessLkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2
The mechanisms that govern the transdifferentiation of lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) are not fully understood. Here, the authors show that EZH2 loss exacerbates the transdifferentiation of ADCs to SCCs as a result of chromatin changes that lead to expression of squamous differentiation genes.
- Haikuo Zhang
- , Christine Fillmore Brainson
- & Kwok-Kin Wong
-
Article
| Open AccessMonocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade
Myeloid-derived suppressive cells (MDSCs) promote metastasis. Here, the authors show that the monocytic MDSCs subset promotes epithelial to mesenchymal transition at the primary site while the granulocytic subset promotes the reverse transition at the metastatic site enabling dynamic tumour cells plasticity.
- Maria Ouzounova
- , Eunmi Lee
- & Hasan Korkaya
-
Article
| Open AccessA CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer
Super-enhancers (SEs) are big DNA regions regulating the transcription of oncogenes. Here the authors identify two SE regions regulating the expression of CD47, a protein expressed by cancer cells to avoid phagocytosis by macrophages, thus suggesting a potential mechanism of immune surveillance escape.
- Paola A. Betancur
- , Brian J. Abraham
- & Irving L. Weissman
-
Article
| Open AccessUSP9X regulates centrosome duplication and promotes breast carcinogenesis
USP9X is a deubiquitinating enzyme with many known substrates and functions; it has been linked to cancer but the mechanisms remain unclear. Here Liet al. report that USP9X stabilizes the centrosomal protein CEP131 leading to centrosome amplification and breast cancer development.
- Xin Li
- , Nan Song
- & Lei Shi
-
Article
| Open AccessInhibiting the system xC−/glutathione axis selectively targets cancers with mutant-p53 accumulation
Efficient therapeutic strategies to target mutant-p53 cancers are needed. Here, the authors demonstrate the molecular mechanism through which mutant-p53 tumours are susceptible to oxidative damage and propose a potential strategy for targeting such cancers by inhibiting the SLC7A11-glutathione axis.
- David S. Liu
- , Cuong P. Duong
- & Nicholas J. Clemons
-
Article
| Open AccessProteogenomic integration reveals therapeutic targets in breast cancer xenografts
Patient-derived xenografts recapitulate major genomic signatures and transcriptome profiles of their original tumours. Here, the authors, performing proteomic and phosphoproteomic analyses of 24 breast cancer PDX models, demonstrate that druggable candidates can be identified based on a comprehensive proteogenomic profiling.
- Kuan-lin Huang
- , Shunqiang Li
- & Li Ding
-
Article
| Open AccessRational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy
Anti-PD-L1 therapy often fails in cancers with minimal lymphocytic infiltrates and low PD-L1 expression. Here, the authors show that an oncolytic virus increases PD-L1 expression in cancer models and that the combination with an anti-PD-L1 antibody enhances therapy by increasing the infiltration of activated T cells, and reducing exhausted T cells.
- Zuqiang Liu
- , Roshni Ravindranathan
- & David L. Bartlett
-
Correspondence
| Open AccessCorrespondence: Reply to ‘Oncogenic MYC persistently upregulates the molecular clock component REV-ERBα’
- Anton Shostak
- , Bianca Ruppert
- & Michael Brunner
-
Correspondence
| Open AccessCorrespondence: Oncogenic MYC persistently upregulates the molecular clock component REV-ERBα
- Brian J. Altman
- , Annie L. Hsieh
- & Chi V. Dang
-
Article
| Open AccessProfiling protein expression in circulating tumour cells using microfluidic western blotting
Circulating tumour cells (CTCs) are rare cells found in the blood of certain cancer patients. Here, the authors develop a cytometry tool that appends a microfluidic western blot to a CTC isolation workflow and apply it to profile a panel of proteins in single CTCs isolated from ER+ breast cancer patients.
- Elly Sinkala
- , Elodie Sollier-Christen
- & Amy E. Herr
-
Article
| Open AccessPolymeric mechanical amplifiers of immune cytokine-mediated apoptosis
Fluid shear stress plays a critical role in receptor-mediated signalling and has been shown to sensitize cancer cells to apoptosis. Here, Mitchellet al. introduce polymer micro- and nanoparticles tethered to tumour cells to amplify fluid shear stress effects, and find that they can enhance immune cytokine-mediated apoptosis of tumour cells in vitro and in vivo.
- Michael J. Mitchell
- , Jamie Webster
- & Robert Langer
-
Article
| Open AccessCirculating tumour DNA reflects treatment response and clonal evolution in chronic lymphocytic leukaemia
Disease monitoring of chronic lymphocytic leukaemia (CLL) is a challenge. Here, the authors show that serial ctDNA analysis in 32 CLL patients allows monitoring of clonal dynamics over time, and identifies the emergence of genomic changes associated with Richter’s syndrome.
- Paul Yeh
- , Tane Hunter
- & Sarah-Jane Dawson
-
Article
| Open AccessCombined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth
Activation of Toll-like receptor (TLR) is generally associated with increased immune activity. Here, the authors show, using syngeneic mouse models, that combined deficiency of TLR 3/7/9 in the host induces an inflamed tumour phenotype and results in T cell dependent tumour regression after an initial growth.
- Johanna C. Klein
- , Katrin Moses
- & Sven Brandau
-
Article
| Open AccessTranslational reprogramming in tumour cells can generate oncoselectivity in viral therapies
mRNA translational control by CPEBs is reactivated in cancer. Here, the authors show that the insertion of CPE regulatory sequences in the 3′ UTR of the E1A viral gene induces oncoselectivity, with oncolytic potency in cancer cells but attenuated toxicity in normal tissues.
- Eneko Villanueva
- , Pilar Navarro
- & Cristina Fillat
Browse broader subjects
Browse narrower subjects
- Bone cancer
- Breast cancer
- Cancer epidemiology
- Cancer genetics
- Cancer genomics
- Cancer imaging
- Cancer metabolism
- Cancer microenvironment
- Cancer models
- Cancer of unknown primary
- Cancer prevention
- Cancer screening
- Cancer stem cells
- Cancer therapy
- CNS cancer
- Cysts
- Embryonal neoplasms
- Endocrine cancer
- Eye cancer
- Gastrointestinal cancer
- Germ cell tumours
- Gynaecological cancer
- Haematological cancer
- Hamartoma
- Head and neck cancer
- Lung cancer
- Mesothelioma
- Metastasis
- Oncogenes
- Oral cancer
- Paediatric cancer
- Sarcoma
- Skin cancer
- Testicular cancer
- Tumour angiogenesis
- Tumour biomarkers
- Tumour heterogeneity
- Tumour immunology
- Tumour-suppressor proteins
- Tumour virus infections
- Urological cancer