Featured
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A vertebral skeletal stem cell lineage driving metastasis
Vertebral osteoblasts in mouse and human are formed from a precursor skeletal stem cell population that is distinct from long bone skeletal stem cells in function, location and transcriptional programme.
- Jun Sun
- , Lingling Hu
- & Matthew B. Greenblatt
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Article
| Open AccessNon-cell-autonomous cancer progression from chromosomal instability
Chromosomal instability in cancer is linked to endoplasmic reticulum stress signalling, immune suppression and metastasis, which is mediated by the cGAS–STING pathway, suppression of which can reduce metastasis.
- Jun Li
- , Melissa J. Hubisz
- & Samuel F. Bakhoum
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Article |
Pharmacological targeting of netrin-1 inhibits EMT in cancer
Netrin-1 is upregulated in cancer models that undergo spontaneous epithelial-to-mesenchymal transition, and its targeting blocks the progression of tumour cells to a late mesenchymal state, suggesting possible therapeutic applications.
- Justine Lengrand
- , Ievgenia Pastushenko
- & Cédric Blanpain
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Article |
Histone demethylase KDM5D upregulation drives sex differences in colon cancer
A murine colorectal cancer (CRC) model shows that mutant KRAS-STAT4-mediated upregulation of Y chromosome KDM5D contributes to the sex differences in KRAS-mutant CRC, providing an actionable therapeutic strategy for metastasis risk reduction for men afflicted with KRAS-mutant CRC.
- Jiexi Li
- , Zhengdao Lan
- & Ronald A. DePinho
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Article |
Tumour extracellular vesicles and particles induce liver metabolic dysfunction
Remote tumours cause liver dysfunction by releasing extracellular vesicles and particles containing palmitic acid, which induces TNF signalling in Kupffer cells, resulting in inflammation, fatty deposits and metabolic dysregulation, thus both reducing the efficacy and increasing the toxicity of chemotherapies.
- Gang Wang
- , Jianlong Li
- & David Lyden
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Article
| Open AccessPan-cancer whole-genome comparison of primary and metastatic solid tumours
The genomic differences between primary and metastatic tumours are assessed across 23 cancer types using pan-cancer whole-genome analysis.
- Francisco Martínez-Jiménez
- , Ali Movasati
- & Arne Van Hoeck
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Article |
Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA
Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.
- Christopher Abbosh
- , Alexander M. Frankell
- & Charles Swanton
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Article
| Open AccessThe evolution of non-small cell lung cancer metastases in TRACERx
A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.
- Maise Al Bakir
- , Ariana Huebner
- & Charles Swanton
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Article |
STING inhibits the reactivation of dormant metastasis in lung adenocarcinoma
STING signalling is activated in metastatic cancer cells that exit from an immune-evasive dormant state, blocking their progression and cancer relapse.
- Jing Hu
- , Francisco J. Sánchez-Rivera
- & Joan Massagué
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Article
| Open AccessRBFOX2 modulates a metastatic signature of alternative splicing in pancreatic cancer
Analysis of messenger RNA splicing in a large cohort of pancreatic ductal adenocarcinoma tumours identifies differential splicing correlating with disease progression, associated with the the splicing regulator RBFOX2.
- Amina Jbara
- , Kuan-Ting Lin
- & Rotem Karni
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Article |
A cellular hierarchy in melanoma uncouples growth and metastasis
A hierarchical model of melanoma tumour growth mirrors the cellular and molecular logic of cell-fate specification and differentiation of the underlying embryonic neural crest, and suggests that the ability to support growth and metastasis are limited to distinct pools of cells.
- Panagiotis Karras
- , Ignacio Bordeu
- & Jean-Christophe Marine
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Article |
The metastatic spread of breast cancer accelerates during sleep
A study of patients with breast cancer and mouse models demonstrates that most circulating tumour cells are generated during the rest phase of the circadian rhythm, and that these cells are highly prone to metastasize.
- Zoi Diamantopoulou
- , Francesc Castro-Giner
- & Nicola Aceto
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Article |
Stromal changes in the aged lung induce an emergence from melanoma dormancy
Changes in the microenvironment of the aged lung relative to younger lung tissue can lead to the reactivation of dormant melanoma cells through a mechanism that involves a decrease in WNT5A and AXL signalling and an increase in MERTK.
- Mitchell E. Fane
- , Yash Chhabra
- & Ashani T. Weeraratna
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Article |
PHGDH heterogeneity potentiates cancer cell dissemination and metastasis
PHDGH heterogeneity in primary tumours could be a sign of tumour aggressiveness.
- Matteo Rossi
- , Patricia Altea-Manzano
- & Sarah-Maria Fendt
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Article |
Dietary palmitic acid promotes a prometastatic memory via Schwann cells
Palmitic acid induces stable transcriptional and chromatin changes that lead to long-term stimulation of metastasis in orthotopic models of cancer through the secretion by tumour-associated Schwann cells of a specialized proregenerative extracellular matrix, the ablation of which inhibits metastasis initiation.
- Gloria Pascual
- , Diana Domínguez
- & Salvador Aznar Benitah
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Article
| Open AccessA metastasis map of human cancer cell lines
A method in which pooled barcoded human cancer cell lines are injected into a mouse xenograft model enables simultaneous mapping of the metastatic potential of multiple cell lines, and shows that breast cancer cells that metastasize to the brain have altered lipid metabolism.
- Xin Jin
- , Zelalem Demere
- & Todd R. Golub
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Article |
Tumoural activation of TLR3–SLIT2 axis in endothelium drives metastasis
Expression of the axon-guidance gene Slit2 in endothelium, induced by endothelial sensing of tumour-derived double-stranded RNA, promotes metastatic dissemination in mouse models of breast and lung cancer.
- Bernardo Tavora
- , Tobias Mederer
- & Sohail F. Tavazoie
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Article |
Pervasive chromosomal instability and karyotype order in tumour evolution
Chromosomal instability enables the continuous selection of somatic copy number alterations, which are established as ordered events that often occur in parallel, throughout tumour evolution and metastasis.
- Thomas B. K. Watkins
- , Emilia L. Lim
- & Charles Swanton
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Article |
Lymph protects metastasizing melanoma cells from ferroptosis
Melanoma cells undergo less oxidative stress and less ferroptosis in lymph than in blood, owing to higher levels of oleic acid in lymph, and thus exposure to the lymphatic environment increases subsequent metastasis through blood.
- Jessalyn M. Ubellacker
- , Alpaslan Tasdogan
- & Sean J. Morrison
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Article |
Metabolic heterogeneity confers differences in melanoma metastatic potential
Differences in MCT1 function among melanoma cells confer differences in oxidative stress resistance and metastatic potential.
- Alpaslan Tasdogan
- , Brandon Faubert
- & Sean J. Morrison
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Article |
Synaptic proximity enables NMDAR signalling to promote brain metastasis
Breast-to-brain metastasis is enabled by activation of an N-methyl-d-aspartate receptor, which is achieved via the formation of pseudo-tripartite synapses between cancer cells and glutamatergic neurons.
- Qiqun Zeng
- , Iacovos P. Michael
- & Douglas Hanahan
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Letter |
E-cadherin is required for metastasis in multiple models of breast cancer
Although E-cadherin loss promotes tumour-cell invasion in mouse and human models of invasive ductal carcinoma, E-cadherin expression prevents oxidative-stress-mediated apoptosis during detachment and is essential for metastasis.
- Veena Padmanaban
- , Ilona Krol
- & Andrew J. Ewald
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Article |
Metastatic-niche labelling reveals parenchymal cells with stem features
A cell-penetrating fluorescent marker is used to label cells in the metastatic tumour microenvironment, revealing a variety of cell types including parenchymal cells with lung stem-cell characteristics.
- Luigi Ombrato
- , Emma Nolan
- & Ilaria Malanchi
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Letter |
Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis
Loss of p53 in mouse models of breast cancer leads to activation of WNT signalling, which promotes metastatic spread by inducing systemic neutrophilic inflammation.
- Max D. Wellenstein
- , Seth B. Coffelt
- & Karin E. de Visser
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Letter |
Glucocorticoids promote breast cancer metastasis
In patient-derived xenograft models of breast cancer in mice, an increase in stress hormones during progression or treatment with their synthetic derivatives activates the glucocorticoid receptor, and results in increased metastatic colonization and reduced survival.
- Milan M. S. Obradović
- , Baptiste Hamelin
- & Mohamed Bentires-Alj
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Letter |
Hepatocytes direct the formation of a pro-metastatic niche in the liver
Pancreatic cancer activates IL-6–STAT3 signalling in hepatocytes to induce the formation of a pro-metastatic niche in the liver.
- Jae W. Lee
- , Meredith L. Stone
- & Gregory L. Beatty
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Letter |
Breast cancer cells rely on environmental pyruvate to shape the metastatic niche
Exogenous pyruvate is needed for breast cancer cells to form metastases, and the inhibition of pyruvate metabolism impairs collagen hydroxylation and the growth of lung metastases in different mouse models.
- Ilaria Elia
- , Matteo Rossi
- & Sarah-Maria Fendt
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Letter |
Asparagine bioavailability governs metastasis in a model of breast cancer
In a mouse model of breast cancer, asparagine bioavailability strongly influences metastasis and this is correlated with the production of proteins that regulate the epithelial-to-mesenchymal transition, which provides at least one potential mechanism for how a single amino acid could regulate metastatic progression.
- Simon R. V. Knott
- , Elvin Wagenblast
- & Gregory J. Hannon
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Article |
Chromosomal instability drives metastasis through a cytosolic DNA response
In chromosomally unstable tumour cells, rupture of micronuclei exposes genomic DNA and activates the cGAS–STING cytosolic DNA-sensing pathway, thereby promoting metastasis.
- Samuel F. Bakhoum
- , Bryan Ngo
- & Lewis C. Cantley
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Brief Communications Arising |
Fischer et al. reply
- Kari R. Fischer
- , Nasser K. Altorki
- & Dingcheng Gao
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Brief Communications Arising |
Upholding a role for EMT in pancreatic cancer metastasis
- Nicole M. Aiello
- , Thomas Brabletz
- & Ben Z. Stanger
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Brief Communications Arising |
Upholding a role for EMT in breast cancer metastasis
- Xin Ye
- , Thomas Brabletz
- & Robert A. Weinberg
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Article |
Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution
Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.
- Christopher Abbosh
- , Nicolai J. Birkbak
- & Charles Swanton
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Article |
A distinct role for Lgr5+ stem cells in primary and metastatic colon cancer
Ablation of Lgr5+ cancer stem cells does not result in regression of primary colorectal tumours, but prevents the formation and maintenance of metastasis in the liver.
- Felipe de Sousa e Melo
- , Antonina V. Kurtova
- & Frederic J. de Sauvage
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Letter |
Genome-wide in vivo screen identifies novel host regulators of metastatic colonization
Screening mutant mouse lines using a genome-wide in vivo assay identifies microenvironmental regulators of metastatic colonization and defines SPNS2 as an important mediator of lung colonization.
- Louise van der Weyden
- , Mark J. Arends
- & David J. Adams
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Article |
Early dissemination seeds metastasis in breast cancer
Two related papers show that cells disseminated from malignant lesions at early time points during tumorigenesis can contribute to metastases at distant organs and provide insights into the molecular basis of dissemination.
- Hedayatollah Hosseini
- , Milan M. S. Obradović
- & Christoph A. Klein
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Article |
Targeting metastasis-initiating cells through the fatty acid receptor CD36
Human oral carcinoma cells expressing high levels of the fatty acid receptor CD36 initiate metastasis in mouse models, and metastasis is increased by palmitic acid or a fatty diet and decreased by blockade of CD36.
- Gloria Pascual
- , Alexandra Avgustinova
- & Salvador Aznar Benitah
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Letter |
Genomic evolution and chemoresistance in germ-cell tumours
Genomic analyses show that primary germ-cell tumours are highly enriched for chromosomal reciprocal loss of heterozygosity, mutations in KRAS and have high mitochondrial priming, providing insight into chemosensitivity and the evolution of chemoresistance in this disease.
- Amaro Taylor-Weiner
- , Travis Zack
- & Eliezer M Van Allen
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Letter |
A PGC1α-mediated transcriptional axis suppresses melanoma metastasis
PGC1α suppresses melanoma metastasis and promotes growth and survival in primary tumours, whilst inhibition of PGC1α induces increased invasion and metastasis.
- Chi Luo
- , Ji-Hong Lim
- & Pere Puigserver
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Letter |
HER2 expression identifies dynamic functional states within circulating breast cancer cells
Patient-derived circulating tumour cells are used to characterize the dynamics and underlying plasticity of HER2 expression in non-HER2-amplified breast tumours.
- Nicole Vincent Jordan
- , Aditya Bardia
- & Daniel A. Haber
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Letter |
Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis
Human and murine tumour cells induce programmed necrosis (necroptosis) of endothelial cells, which promotes tumour cell extravasation and metastasis.
- Boris Strilic
- , Lida Yang
- & Stefan Offermanns
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Article |
Carcinoma–astrocyte gap junctions promote brain metastasis by cGAMP transfer
A heterotypic cell interaction between astrocytes and tumour cells colonizing the brain is discovered; by establishing gap junctions, tumour cells trigger the activation of innate immune response signalling in astrocytes, which results in the secretion of factors that support growth and chemoresistance in brain metastatic cells.
- Qing Chen
- , Adrienne Boire
- & Joan Massagué
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Letter |
sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance
Aged fibroblasts release a Wnt antagonist, sFRP2, which drives a signalling cascade in melanoma cells, leading to increased metastasis and reduced effectiveness of targeted therapy.
- Amanpreet Kaur
- , Marie R. Webster
- & Ashani T. Weeraratna
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Article |
Divergent clonal selection dominates medulloblastoma at recurrence
To address the question of whether a recurrent tumour is genetically similar to the tumour at diagnosis, the evolution of medulloblastoma has been studied in both an in vivo mouse model of clinical tumour therapy as well as in humans with recurrent disease; targeted tumour therapies are usually based on targets present in the tumour at diagnosis but the results from this study indicate that post-treatment recurring tumours (compared with the tumour at diagnosis) have undergone substantial clonal divergence of the initial dominant tumour clone.
- A. Sorana Morrissy
- , Livia Garzia
- & Michael D. Taylor
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Article |
Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance
An epithelial-to-mesenchymal transition (EMT) lineage-tracing system in a mouse model of breast-to-lung metastasis reveals that although some cells undergo EMT in a primary epithelial tumour, the lung metastases mainly arise from cells that have not undergone EMT; in addition, cells that have undergone EMT appear more resistant to chemotherapy.
- Kari R. Fischer
- , Anna Durrans
- & Dingcheng Gao
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Article |
Tumour exosome integrins determine organotropic metastasis
Exosomes originating from lung-, liver- and brain-tropic tumour cells are preferentially incorporated by specific resident cells of the target organs, thus preparing the site for metastasis; the expression of distinct combinations of exosomal integrin proteins determines the exosomal targeting to each of the three organs, and blocking these integrins reduces organotropic exosome uptake by the target organs, thereby reducing the likelihood of organotropic metastasis.
- Ayuko Hoshino
- , Bruno Costa-Silva
- & David Lyden
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Letter |
Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth
Expression of the tumour suppressor PTEN in disseminated primary tumour cells is lost after tumour cells metastasize to the brain, with downregulation instigated by microRNAs from astrocytes, which are transferred from cell to cell by exosomes; these findings reveal the dynamic nature of metastatic cancer cells when adapting to a new tissue environment.
- Lin Zhang
- , Siyuan Zhang
- & Dihua Yu
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Article |
Oxidative stress inhibits distant metastasis by human melanoma cells
Human melanoma cells grown in mice experience high levels of oxidative stress in the bloodstream such that few metastasizing cells survive to form tumours; the rare melanoma cells that successfully metastasize undergo metabolic changes that increase their capacity to withstand this stress, and antioxidant treatments increase metastasis formation by human melanoma cells, while inhibiting antioxidant pathways had the reverse effect.
- Elena Piskounova
- , Michalis Agathocleous
- & Sean J. Morrison
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Letter |
Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells
Single-cell analysis of gene expression in metastatic cells from distinct human breast tumour models shows that early metastatic cells possess basal, stem and mesenchymal cell properties, whereas advanced metastatic cells have more proliferative properties and are more mature, enabling them to be targeted with an anti-proliferative compound.
- Devon A. Lawson
- , Nirav R. Bhakta
- & Zena Werb