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Article
| Open Accessγδ T cells are effectors of immunotherapy in cancers with HLA class I defects
γδ T cells contribute to the response to immune checkpoint blockade treatment in patients with HLA-class-I-negative DNA mismatch repair-deficient colon cancers. .
- Natasja L. de Vries
- , Joris van de Haar
- & Emile E. Voest
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Article |
Colon tumour cell death causes mTOR dependence by paracrine P2X4 stimulation
Chemotherapy-induced death of colon cancer cells causes ATP release triggering P2X4 to mediate an mTOR-dependent pro-survival program in neighbouring cancer cells, which renders them sensitive to mTOR inhibition.
- Mark Schmitt
- , Fatih Ceteci
- & Florian R. Greten
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Article
| Open AccessPhenotypic plasticity and genetic control in colorectal cancer evolution
Intratumour genetic ancestry only infrequently affects gene expression traits and subclonal evolution in colorectal cancer, with most genetic intratumour variation having no detected phenotypic consequence and transcriptional plasticity being widespread within a tumour.
- Jacob Househam
- , Timon Heide
- & Trevor A. Graham
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Article
| Open AccessAntibody targeting of E3 ubiquitin ligases for receptor degradation
Membrane-bound E3 ubiquitin ligases RNF43 and ZNRF3 are overexpressed in colorectal cancer, and can be repurposed using proteolysis-targeting antibodies (PROTABs) to selectively degrade cell-surface receptors in tumours.
- Hadir Marei
- , Wen-Ting K. Tsai
- & Felipe de Sousa e Melo
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Article |
NOTUM from Apc-mutant cells biases clonal competition to initiate cancer
NOTUM from Apc-mutant cells acts as a key mediator during the early stages of mutation fixation and drives the formation of intestinal adenomas.
- Dustin J. Flanagan
- , Nalle Pentinmikko
- & Owen J. Sansom
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Review Article |
Host–microbiota maladaptation in colorectal cancer
This Review describes the interplay between host genetics, host immunity and the gut microbiome in the modulation of colorectal cancer, and discusses the role of specific bacterial species and metabolites alongside technological advances that will facilitate more in-depth investigation of the microbiome in disease.
- Alina Janney
- , Fiona Powrie
- & Elizabeth H. Mann
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Article |
Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis
In patients with ulcerative colitis, chronic inflammation can lead to remodelling of the colorectal epithelium through positive selection of clones with mutations in genes related to IL-17 signalling, which, however, might be negatively selected during colitis-associated carcinogenesis.
- Nobuyuki Kakiuchi
- , Kenichi Yoshida
- & Seishi Ogawa
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Article |
The landscape of somatic mutation in normal colorectal epithelial cells
Genome sequencing of hundreds of normal colonic crypts from 42 individuals sheds light on mutational processes and driver mutations in normal colorectal epithelial cells.
- Henry Lee-Six
- , Sigurgeir Olafsson
- & Michael R. Stratton
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Letter |
Interleukin-22 protects intestinal stem cells against genotoxic stress
Sporadic inactivation of the interleukin-22 receptor in the intestinal epithelium of the mouse shows that IL-22 is required for effective activation of the DNA damage response following DNA damage.
- Konrad Gronke
- , Pedro P. Hernández
- & Andreas Diefenbach
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Article |
Intra-tumour diversification in colorectal cancer at the single-cell level
Organoids derived from individual cells from colorectal cancers and adjacent normal tissue are used to investigate intra-tumour diversification at the genomic, epigenetic and functional levels.
- Sophie F. Roerink
- , Nobuo Sasaki
- & Hans Clevers
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Letter |
TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis
A combination of TGFβ inhibition and checkpoint-inhibition therapy provokes a potent cytotoxic response against metastatic tumours derived from colorectal cancers in mice.
- Daniele V. F. Tauriello
- , Sergio Palomo-Ponce
- & Eduard Batlle
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Article |
High-fat diet enhances stemness and tumorigenicity of intestinal progenitors
A high-fat diet increases the number of intestinal stem cells in mammals, both in vivo and in intestinal organoids; a pathway that involves PPAR-δ confers organoid-initiating capacity to non-stem cells and induces them to form in vivo tumours after loss of the Apc tumour suppressor.
- Semir Beyaz
- , Miyeko D. Mana
- & Ömer H. Yilmaz
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Letter |
Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function
Antibody-mediated inhibition of R-spondin-3 in colorectal tumours decreases tumour growth and promotes differentiation—these effects are associated with a decrease in expression of genes associated with stem-cell function.
- Elaine E. Storm
- , Steffen Durinck
- & Frederic J. de Sauvage
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Article |
Proteogenomic characterization of human colon and rectal cancer
Proteome analysis of The Cancer Genome Atlas (TCGA) colorectal cancer specimens reveals that DNA- or RNA-level measurements cannot reliably predict protein abundance, colorectal tumours can be separated into distinct proteotypes, and that copy number alterations drive mRNA abundance changes but few extend to protein-level changes.
- Bing Zhang
- , Jing Wang
- & R. Reid Townsend
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Letter |
IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine
IL-22 is one of the factors that, although important for wound healing, also promote tumorigenesis; the regulation of IL-22BP, the IL-22 binding protein, via the NLRP3 and NLRP6 inflammasomes provides an unanticipated mechanism, controlling IL-22 and thereby the development of colon cancer.
- Samuel Huber
- , Nicola Gagliani
- & Richard A. Flavell
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Letter
| Open AccessRecurrent R-spondin fusions in colon cancer
Exomes, transcriptomes and copy-number alterations in a sample of more than 70 primary human colonic tumours were analysed in an attempt to characterize the genomic landscape; in addition to finding alterations in genes associated with commonly mutated signalling pathways, recurrent gene fusions involving R-spondin family members were also found to occur in approximately 10% of colonic tumours, revealing a potential new therapeutic target.
- Somasekar Seshagiri
- , Eric W. Stawiski
- & Frederic J. de Sauvage
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Letter |
Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR
Inhibition of activated BRAF has been ineffective in colon cancers with the mutation; here, this is shown to be due to the feedback activation of the epidermal growth factor receptor (EGFR) in response to BRAF inhibition.
- Anirudh Prahallad
- , Chong Sun
- & René Bernards
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Research Highlights |
Stem-cell genes linked to relapse
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Research Highlights |
Microbiology: A strain on the relationship
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Research Highlights |
Immunology: Inflammatory good guys