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Article
| Open Access
MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis
The double-strand break sensor MRE11 is identified as a pivotal mediator of cGAS activation in response to multiple types of DNA damage.
- Min-Guk Cho
- , Rashmi J. Kumar
- & Gaorav P. Gupta
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Article |
Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides
The tumour-specific circular RNA FAM53B is highly immunogenic and can induce anti-tumour responses in mouse models of breast cancer and melanoma, expanding the repertoire of anticancer targets for development.
- Di Huang
- , Xiaofeng Zhu
- & Erwei Song
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Article |
Stepwise requirements for polymerases δ and θ in theta-mediated end joining
Polymerase delta is required for multiple steps in polymerase theta-dependent repair of chromosome breaks, a pathway targeted in cancer therapy.
- Susanna Stroik
- , Juan Carvajal-Garcia
- & Dale A. Ramsden
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Article
| Open Access
Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis
In mitosis, genome integrity is maintained by DNA polymerase theta-dependent repair of DNA double-strand breaks, which is regulated by Polo-like kinase 1 activity.
- Camille Gelot
- , Marton Tibor Kovacs
- & Raphael Ceccaldi
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Article
| Open Access
Spatial predictors of immunotherapy response in triple-negative breast cancer
Imaging mass cytometry is used to map the multicellular dynamics of immune checkpoint blockade-treated triple-negative breast cancer, finding that key proliferative fractions and cell–cell interactions drive response, and immunotherapy distinctively remodels tumour structure.
- Xiao Qian Wang
- , Esther Danenberg
- & H. Raza Ali
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Article
| Open Access
Long-molecule scars of backup DNA repair in BRCA1- and BRCA2-deficient cancers
Linked-read whole-genome sequencing reveals patterns of structural DNA variants that are specific to homologous recombination deficiency and can be used to distinguish between BRCA1- and BRCA2-deficient phenotypes.
- Jeremy Setton
- , Kevin Hadi
- & Marcin Imieliński
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Article
| Open Access
Evolutionary histories of breast cancer and related clones
By using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, unique evolutionary histories of breast cancers harbouring a common driver alteration are shown, providing new insight into how breast cancer evolves.
- Tomomi Nishimura
- , Nobuyuki Kakiuchi
- & Seishi Ogawa
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Structure and function of the RAD51B–RAD51C–RAD51D–XRCC2 tumour suppressor
Structural and biochemical studies of the RAD51B–RAD51C–RAD51D–XRCC2 complex reveal that it uses coupled RAD51B and RAD51C ATPase activities to promote the nucleation and extension of RAD51 nucleoprotein filaments.
- Luke A. Greenhough
- , Chih-Chao Liang
- & Stephen C. West
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Article
| Open Access
ERα-associated translocations underlie oncogene amplifications in breast cancer
An analysis of 780 breast cancer genomes shows that focal amplifications are frequently preceded by dicentric chromosome formation from inter-chromosomal translocations associated with oestrogen receptor binding, which leads to chromosome bridge formation and breakage, initiating the amplification process.
- Jake June-Koo Lee
- , Youngsook Lucy Jung
- & Peter J. Park
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PI3Kβ controls immune evasion in PTEN-deficient breast tumours
A mouse model of invasive breast cancer in which Pten and Trp53 are simultaneously inactivated links PTEN loss with STAT3 activation and indicates that immune escape in PTEN-null tumours is mediated by PI3Kβ.
- Johann S. Bergholz
- , Qiwei Wang
- & Jean J. Zhao
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Article
| Open Access
Spatial genomics maps the structure, nature and evolution of cancer clones
A workflow centred around base-specific in situ sequencing generates detailed maps of, and can phenotypically characterize, the unique set of subclones of cancers.
- Artem Lomakin
- , Jessica Svedlund
- & Lucy R. Yates
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Article
| Open Access
Single-cell genomic variation induced by mutational processes in cancer
Single-cell whole-genome sequencing shows that 'foreground' cell-to-cell structural variation and alterations in copy number are associated with genomic diversity and evolution in triple-negative breast and high-grade serous ovarian cancers.
- Tyler Funnell
- , Ciara H. O’Flanagan
- & Samuel Aparicio
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Genomics to select treatment for patients with metastatic breast cancer
Targeted therapies matched to genomics improved progression-free survival when genomic alterations were classified as level I/II (according to ESCAT), and genomics should thus be driven by target actionability in patients with metastatic breast cancer.
- Fabrice Andre
- , Thomas Filleron
- & Ivan Bieche
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Article
| Open Access
Truncated FGFR2 is a clinically actionable oncogene in multiple cancers
Truncation of exon 18 of FGFR2 (FGFR2ΔE18) is a potent driver mutation in mice and humans, and FGFR-targeted therapy should be considered for patients with cancer expressing stable FGFR2ΔE18 variants.
- Daniel Zingg
- , Jinhyuk Bhin
- & Jos Jonkers
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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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cGAS–STING drives the IL-6-dependent survival of chromosomally instable cancers
The survival of cells with chromosomal instability (CIN) depends on the cGAS–STING pathway, in which IL-6 and its receptor have a key role; this vulnerability can be exploited to treat tumours that display CIN.
- Christy Hong
- , Michael Schubert
- & Floris Foijer
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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
| Open Access
Effective drug combinations in breast, colon and pancreatic cancer cells
A survey of potency and efficacy of 2,025 clinically relevant two-drug combinations against 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines identifies rare synergistic effects of anticancer drugs, informing rational combination treatments for specific cancer subtypes.
- Patricia Jaaks
- , Elizabeth A. Coker
- & Mathew J. Garnett
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Article
| Open Access
Multi-omic machine learning predictor of breast cancer therapy response
Integration of pre-treatment tumour features in predictive models using machine learning could inform on response to therapy.
- Stephen-John Sammut
- , Mireia Crispin-Ortuzar
- & Carlos Caldas
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Structures of the HER2–HER3–NRG1β complex reveal a dynamic dimer interface
Cryo-electron microscopy structures of the HER2–HER3–NRG1β complex reveal a dynamic HER2–HER3 interface and explain the mechanism for the activating HER2 cancer mutations.
- Devan Diwanji
- , Raphael Trenker
- & Natalia Jura
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Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion
In mouse models of triple-negative breast cancer, the extracellular domain of the collagen receptor DDR1 has a role in tumour defence against the immune system, by aligning collagen fibres to obstruct immune infiltration.
- Xiujie Sun
- , Bogang Wu
- & Rong Li
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Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy
Liver-resident natural killer (NK) cells sustain the dormancy of disseminated breast cancer cells, and a decrease in NK cells and increase in activated hepatic stellate cells is associated with the formation of liver metastases.
- Ana Luísa Correia
- , Joao C. Guimaraes
- & Mohamed Bentires-Alj
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Breast tumours maintain a reservoir of subclonal diversity during expansion
Single-cell analysis of genomes from primary human breast tumours and cell lines shows that chromosomal aberrations continue to evolve during primary tumour expansion, resulting in a milieu of subclones within the tumour.
- Darlan C. Minussi
- , Michael D. Nicholson
- & Nicholas E. Navin
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Matters Arising |
Reply to: Hippo signalling maintains ER expression and ER+ breast cancer growth
- Adrian Britschgi
- , Joana Pinto Couto
- & Mohamed Bentires-Alj
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Matters Arising |
Hippo signalling maintains ER expression and ER+ breast cancer growth
- Shenghong Ma
- , Zhengming Wu
- & Kun-Liang Guan
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Article |
BRCA1 and RNAi factors promote repair mediated by small RNAs and PALB2–RAD52
Single-stranded, DNA-damage-associated small RNAs generated by a BRCA1–RNA-interference complex promote PALB2–RAD52-mediated DNA repair at transcriptional termination pause sites that contain R-loops and are rich in single-stranded DNA breaks in both quiescent and proliferating cells.
- Elodie Hatchi
- , Liana Goehring
- & David M. Livingston
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Article
| Open Access
A 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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Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified breast cancer
TRIM37 overexpression promotes centrosome dysfunction that drives genomic instability in breast cancer cell lines containing the recurrent 17q23 amplicon, revealing a vulnerability that can be targeted to eliminate cancer cells.
- Zhong Y. Yeow
- , Bramwell G. Lambrus
- & Andrew J. Holland
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Fasting-mimicking diet and hormone therapy induce breast cancer regression
In mice, periodic fasting or a fasting-mimicking diet enhances the efficacy of endocrine therapy for breast cancer and delays acquired resistance to it; in patients with breast cancer, a fasting-mimicking diet recreates the metabolic changes observed in mice.
- Irene Caffa
- , Vanessa Spagnolo
- & Alessio Nencioni
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DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25
DNA from neutrophil extracellular traps interacts with the transmembrane receptor CCDC25 on cancer cells, activating the ILK-β-parvin pathway to enhance cell motility and promote distant metastases.
- Linbin Yang
- , Qiang Liu
- & Erwei Song
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Article |
The single-cell pathology landscape of breast cancer
A single-cell, spatially resolved analysis of breast cancer demonstrates the heterogeneity of tumour and stroma tissue and provides a more-detailed method of patient classification than the current histology-based system.
- Hartland W. Jackson
- , Jana R. Fischer
- & Bernd Bodenmiller
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International evaluation of an AI system for breast cancer screening
An artificial intelligence (AI) system performs as well as or better than radiologists at detecting breast cancer from mammograms, and using a combination of AI and human inputs could help to improve screening efficiency.
- Scott Mayer McKinney
- , Marcin Sieniek
- & Shravya Shetty
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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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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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Isomerization of BRCA1–BARD1 promotes replication fork protection
BRCA1–BARD1 has a role in replication fork protection that is mediated by a mechanism of phosphorylation-targeted isomerization of BRCA1 and is independent of the canonical interaction between BRCA1 and PALB2.
- Manuel Daza-Martin
- , Katarzyna Starowicz
- & Joanna R. Morris
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Letter |
Genomic characterization of metastatic breast cancers
Patient data from six clinical trials are used to compare the genomic landscapes of breast cancer metastases with those of primary tumours, revealing an increase in mutational burden and clonal diversity.
- François Bertucci
- , Charlotte K. Y. Ng
- & Fabrice André
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Letter |
LLGL2 rescues nutrient stress by promoting leucine uptake in ER+ breast cancer
The polarity protein LLGL2 supports tumour growth in breast cancer by promoting leucine uptake and adaptation to nutrient stress.
- Yasuhiro Saito
- , Lewyn Li
- & Senthil K. Muthuswamy
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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 |
Dynamics of breast-cancer relapse reveal late-recurring ER-positive genomic subgroups
A statistical framework for breast-cancer recurrence uses long-term follow-up data and a knowledge of molecular subcategories to model distinct disease stages and to predict the risk of relapse.
- Oscar M. Rueda
- , Stephen-John Sammut
- & Christina Curtis
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Letter |
Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism
The transcription factor BACH1, which targets mitochondrial metabolism, is expressed at high levels in several types of cancer; reducing its expression in tumours makes them more susceptible to treatment with mitochondrial inhibitors.
- Jiyoung Lee
- , Ali E. Yesilkanal
- & Marsha Rich Rosner
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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 |
Neutrophils escort circulating tumour cells to enable cell cycle progression
The authors show that circulating tumour cells can be found in association with neutrophils, an interaction which supports their proliferation and their ability to seed metastasis.
- Barbara Maria Szczerba
- , Francesc Castro-Giner
- & Nicola Aceto
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Article |
Accurate classification of BRCA1 variants with saturation genome editing
Germline BRCA1 loss-of-function variants are associated with predisposition to early-onset breast and ovarian cancer; here the authors use CRISPR/Cas9 genome editing to functionally assess thousands of BRCA1 variants in order to facilitate the clinical interpretation of these variants.
- Gregory M. Findlay
- , Riza M. Daza
- & Jay Shendure
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Article |
Mechanism of tandem duplication formation in BRCA1-mutant cells
BRCA1, but not BRCA2, suppresses the formation of tandem duplications at stalled replication forks in primary mammalian cells.
- Nicholas A. Willis
- , Richard L. Frock
- & Ralph Scully
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Letter |
CDK4/6 inhibition triggers anti-tumour immunity
Mouse models of breast carcinoma and other solid tumours show that selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors not only induce tumour cell cycle arrest but also promote anti-tumour immunity.
- Shom Goel
- , Molly J. DeCristo
- & Jean J. Zhao
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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 breast cancer metastasis
- Xin Ye
- , Thomas Brabletz
- & Robert A. Weinberg
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Article |
Recurrent and functional regulatory mutations in breast cancer
High-depth sequencing of targeted regions in primary breast cancer identifies mutated promoter elements with recurrent mutations at specific and/or nearby bases, suggesting selection of certain non-coding events.
- Esther Rheinbay
- , Prasanna Parasuraman
- & Gad Getz
