Featured
-
-
Article |
SOX17 enables immune evasion of early colorectal adenomas and cancers
Transcriptomic and chromatin accessibility analyses of naive and transplanted colon cancer organoids in a mouse model reveal a key role for the transcription factor SOX17 in establishing a permissive immune environment for tumour cells.
- Norihiro Goto
- , Peter M. K. Westcott
- & Ömer H. Yilmaz
-
Article |
The extracellular matrix dictates regional competence for tumour initiation
Experiments in mice show that expression of the oncogene SmoM2 induces basal cell carcinoma in the ear epidermis but not in the back skin, and that this difference in susceptibility is regulated by the extracellular matrix.
- Nordin Bansaccal
- , Pauline Vieugue
- & Cédric Blanpain
-
Article |
Lysine catabolism reprograms tumour immunity through histone crotonylation
Glioblastoma stem cells co-opt lysine uptake and degradation to shunt the production of crotonyl-CoA, remodelling the chromatin landscape to evade interferon-induced intrinsic effects on glioblastoma stem cell maintenance and extrinsic effects on immune response.
- Huairui Yuan
- , Xujia Wu
- & Jeremy N. Rich
-
Article |
Human fetal cerebellar cell atlas informs medulloblastoma origin and oncogenesis
Integrated single-cell atlases of human fetal cerebella and MBs show potential cell populations predisposed to transformation and regulatory circuitries underlying tumour cell states and oncogenesis, highlighting hitherto unrecognized transitional progenitor intermediates predictive of disease prognosis.
- Zaili Luo
- , Mingyang Xia
- & Q. Richard Lu
-
Article
| Open AccessRas drives malignancy through stem cell crosstalk with the microenvironment
Aberrant crosstalk between cancer stem cells and their microenvironment triggers angiogenesis and TGFβ signalling, creating conditions that are conducive for hijacking leptin and leptin receptor signalling, which in turn launches downstream PI3K–AKT–mTOR signalling during the benign-to-malignant transition.
- Shaopeng Yuan
- , Katherine S. Stewart
- & Elaine Fuchs
-
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
-
Article |
Cell–matrix interface regulates dormancy in human colon cancer stem cells
A genetic lineage-tracing system in human colorectal organoids identifies a population of dormant cancer cells that persists during chemotherapy and enables cancer regrowth, and the cell-adhesion molecule COL17A1 has a key role in the process of breaking dormancy.
- Yuki Ohta
- , Masayuki Fujii
- & Toshiro Sato
-
Article |
Non-genetic determinants of malignant clonal fitness at single-cell resolution
Non-genetic malignant clonal dominance is a cell-intrinsic and heritable property that underpins clonal output and response to therapy in cancer.
- Katie A. Fennell
- , Dane Vassiliadis
- & Mark A. Dawson
-
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
-
Article |
Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis
In mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, malignant progression and metastasis through the activation of a hybrid epithelial-to-mesenchymal transition phenotype.
- Ievgenia Pastushenko
- , Federico Mauri
- & Cédric Blanpain
-
Letter |
Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion
Leukaemic stem cells in acute myeloid leukaemia are defined by a lack of expression of NKG2D ligands, which mediates their ability to evade surveillance by NK cells.
- Anna M. Paczulla
- , Kathrin Rothfelder
- & Claudia Lengerke
-
Letter |
Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring
A systematic proteomic investigation of disease mediators secreted by pancreatic stellate cells identifies leukaemia inhibitory factor (LIF) as a key factor that acts on cancer cells, promoting tumour progression and chemoresistance.
- Yu Shi
- , Weina Gao
- & Tony Hunter
-
Letter |
Prediction of acute myeloid leukaemia risk in healthy individuals
Individuals who are at high risk of developing acute myeloid leukaemia can be identified years before diagnosis using genetic information from blood samples.
- Sagi Abelson
- , Grace Collord
- & Liran I. Shlush
-
Letter |
Senescence-associated reprogramming promotes cancer stemness
Cellular senescence induced by chemotherapy leads to the acquisition of stemness in cancer cells, which results in enhanced tumour-promoting capacity after forced release or spontaneous escape from the senescent cell-cycle arrest.
- Maja Milanovic
- , Dorothy N. Y. Fan
- & Clemens A. Schmitt
-
Letter |
BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation
The mechanistic basis for the role of the metabolic enzyme BCAA transaminase 1 (BCAT1) in acute myeloid leukaemias.
- Simon Raffel
- , Mattia Falcone
- & Andreas Trumpp
-
Article |
Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy
Using unique barcodes for tumour cells, the authors explore the dynamics of human glioblastoma subpopulations, and suggest that clonal heterogeneity emerges through stochastic fate decisions of a neutral proliferative hierarchy.
- Xiaoyang Lan
- , David J. Jörg
- & Peter B. Dirks
-
Letter |
Tracing the origins of relapse in acute myeloid leukaemia to stem cells
Identification of the cell types from which relapse arises in acute myeloid leukaemia, by following leukaemia propagation from patient-derived leukaemia samples.
- Liran I. Shlush
- , Amanda Mitchell
- & John E. Dick
-
Letter |
A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma
A subset of Kras and p53 mutant cancer cells acts as a Wnt-producing niche for another cancer cell subset, and porcupine inhibition disrupts Wnt secretion in this niche, thereby suppressing proliferative potential and leading to therapeutic benefit.
- Tuomas Tammela
- , Francisco J. Sanchez-Rivera
- & Tyler Jacks
-
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
-
Article |
Visualization and targeting of LGR5+ human colon cancer stem cells
LGR5+ cells in human colorectal cancer tissue xenografted into mice act as cancer stem cells, and differentiated cancer cells can revert to cancer stem cells and express LGR5 after ablation of existing LGR5+ cells.
- Mariko Shimokawa
- , Yuki Ohta
- & Toshiro Sato
-
Article |
Myeloid progenitor cluster formation drives emergency and leukaemic myelopoiesis
During emergency myelopoiesis in mice, clusters of self-renewing granulocyte/macrophage progenitors (GMP) are transiently formed in the bone marrow cavity to produce a burst of myeloid cells; in leukaemia, GMP clusters persist and constantly generate myeloid leukaemia cells.
- Aurélie Hérault
- , Mikhail Binnewies
- & Emmanuelle Passegué
-
Article |
Translation from unconventional 5′ start sites drives tumour initiation
The translation of upstream open reading frames in skin tumour models protects some cancer-related mRNAs from global reductions in protein synthesis during the early stages of tumour initiation, suggesting that unconventional translation has a crucial role in tumorigenesis.
- Ataman Sendoel
- , Joshua G. Dunn
- & Elaine Fuchs
-
Letter |
A 17-gene stemness score for rapid determination of risk in acute leukaemia
A rapid gene signature test (LSC17) that captures stem cell expression programs in acute myeloid leukaemia patients at diagnosis is associated with therapy response and survival, facilitating initial treatment stratification.
- Stanley W. K. Ng
- , Amanda Mitchell
- & Jean C. Y. Wang
-
Letter |
Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma
A single sentence summarizing your paper (websum), which will appear online on the table of contents and in e-alerts, has been provided below. Please check this sentence for accuracy and appropriate emphasis.
- Itay Tirosh
- , Andrew S. Venteicher
- & Mario L. Suvà
-
Letter |
The lipolysis pathway sustains normal and transformed stem cells in adult Drosophila
Attenuating the lipolysis pathway in Drosophila melanogaster by modulation of the COP1–Arf1 signalling complex induced necrosis in stem cells and led to their engulfment by differentiated cells.
- Shree Ram Singh
- , Xiankun Zeng
- & Steven X. Hou
-
Article |
Defining the clonal dynamics leading to mouse skin tumour initiation
Skin stem cells, but not their progenitors, are able to form tumours owing to the ability of oncogene-targeted stem cells to increase symmetric self-renewing division and a higher p53-dependent resistance to apoptosis.
- Adriana Sánchez-Danés
- , Edouard Hannezo
- & Cédric Blanpain
-
Article |
Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells
Leukaemic stem cells (LSCs) are responsible for BCR–ABL-driven chronic myeloid leukaemia relapse; here, p53 and MYC signalling networks are shown to regulate LSCs concurrently, and targeting both these pathways has a synergistic effect in managing the disease.
- Sheela A. Abraham
- , Lisa E. M. Hopcroft
- & Tessa L. Holyoake
-
Letter |
Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma
The stem cell determinant Musashi (Msi) is a key mediator of pancreatic cancer progression and therapy resistance.
- Raymond G. Fox
- , Nikki K. Lytle
- & Tannishtha Reya
-
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
-
Letter |
Neutrophils support lung colonization of metastasis-initiating breast cancer cells
Neutrophils are shown to have a role in driving the metastasis of breast cancer cells to the lung, with neutrophil-derived leukotrienes promoting metastatic initiation in the lung by expanding the sub-pool of cancer cells with high tumorigenic potential.
- Stefanie K. Wculek
- & Ilaria Malanchi
-
Letter |
Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells
The first formal evidence of the shared and independent ability of basal cells and luminal pro-genitors isolated from normal human mammary tissue and transduced with a single oncogene to initiate tumorigeneses when introduced into mice.
- Long V. Nguyen
- , Davide Pellacani
- & Connie J. Eaves
-
Letter |
Distinct EMT programs control normal mammary stem cells and tumour-initiating cells
This study finds that the epithelial-to-mesenchymal (EMT) transition program, which is common to both mammary gland reconstituting stem cells and mammary tumour-initiating cells, is differentially regulated by two distinct EMT factors, Slug and Snail; the findings illustrate that although they appear similar, normal tissue stem cells and tumour-initiating cells are controlled by distinct regulatory processes.
- Xin Ye
- , Wai Leong Tam
- & Robert A. Weinberg
-
Letter |
Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists
Although imatinib gives good clinical results in chronic myeloid leukaemia (CML), residual disease attributed to quiescent CML stem cells remains in many patients; here glitazones are shown to reduce the pool of CML stem cells and achieve lasting disease eradication in CML patients in combination with imatinib.
- Stéphane Prost
- , Francis Relouzat
- & Philippe Leboulch
-
Letter |
Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance
Using human bladder cancer xenograft models, a new mechanism involving an active proliferative response of cancer stem cells to chemotherapy-induced damage is shown, driven by prostaglandin E2 (PGE2) release in a manner similar to PGE2-induced wound repair; pharmacological inhibition of the PGE2/COX2 axis by celecoxib attenuates chemoresistance, suggesting a possible adjunctive therapy for bladder carcinomas.
- Antonina V. Kurtova
- , Jing Xiao
- & Keith Syson Chan
-
Letter |
Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function
KRAS mutations are a driver event of pancreatic ductal adenocarcinoma; here, a subpopulation of dormant tumour cells, relying on oxidative phosphorylation for survival, is shown to be responsible for tumour relapse after treatment targeting the KRAS pathway.
- Andrea Viale
- , Piergiorgio Pettazzoni
- & Giulio F. Draetta
-
Letter |
SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma
Here, in a mouse model of skin squamous cell carcinoma, a key role is demonstrated for the transcription factor SOX2 in the initiation and progression of skin tumours.
- Soufiane Boumahdi
- , Gregory Driessens
- & Cédric Blanpain
-
Outlook |
Comparative biology: Naked ambition
A subterranean species that seems to be cancer-proof is providing promising clues on how we might prevent the disease in humans.
- Sarah Deweerdt
-
Outlook |
Biology: Three known unknowns
Even as cancer therapies improve, basic questions about drug resistance, tumour spread and the role of normal tissue remain unanswered.
- Katherine Bourzac
-
Article |
Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia
The authors identify pre-leukaemic haematopoietic stem cells (HSCs) in patients with acute myeloid leukaemia; these pre-leukaemic HSCs have the capacity of normal multi-lineage haematopoietic differentiation with a competitive growth advantage over wild-type HSCs, and owing to their persistence may serve as a reservoir for therapeutic resistance and relapse.
- Liran I. Shlush
- , Sasan Zandi
- & John E. Dick
-
Outlook |
Stem cells: Bad seeds
Leukaemia treatments must eliminate the versatile cells that can bring the cancer back to life years later.
- Cassandra Willyard
-
Outlook |
Cell banks: Life blood
Stem cells from the umbilical cord are among the latest weapons in the fight against leukaemia.
- Melinda Wenner Moyer
-
News & Views Forum |
Resolving the stem-cell debate
New research backs the contentious idea that solid tumours are not masses of equivalent cells, but instead contain cancer stem cells that support tumour maintenance. Here, two experts provide complementary views on the findings and on the implications for potential therapies. See Letters p.522 & p.527
- Richard J. Gilbertson
- & Trevor A. Graham
-
News |
Cancer stem cells tracked
The master builders that underlie tumour growth may inform treatment strategies.
- Monya Baker
-
Letter |
Defining the mode of tumour growth by clonal analysis
Using genetic lineage tracing, tumour cells are traced in vivo in an unperturbed solid tumour; in a carcinogen-induced papilloma mouse model, cells in these benign lesions are found to mirror the clonal hierarchy organization of normal tissue.
- Gregory Driessens
- , Benjamin Beck
- & Cédric Blanpain
-
Letter |
A restricted cell population propagates glioblastoma growth after chemotherapy
By using a GFP reporter protein expressed selectively in neural stem cells in a mouse model of glioblastoma, a small subset of GFP-positive glioma cells is shown to be responsible for re-growth of tumours after chemotherapy.
- Jian Chen
- , Yanjiao Li
- & Luis F. Parada
-
Letter |
Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development
The binding of angiopoietin-like proteins to immune-inhibitory receptors maintains ‘stemness’ of haematopoietic stem cells and supports leukaemia development.
- Junke Zheng
- , Masato Umikawa
- & Cheng Cheng Zhang
-
Research Highlights |
Drug drives cancer stem cells
-
Outlook |
Tumorigenesis: Testing ground for cancer stem cells
Multiple myeloma is the ideal disease to study a controversial theory about the biology of cancer — and how to cure it.
- Cathryn Delude
-
Letter |
Interactions between cancer stem cells and their niche govern metastatic colonization
For the initiation of metastasis, there must be a small population of cancer stem cells at the secondary site and, to maintain this population and allow proliferation, infiltrating cancer cells must induce the expression of stromal periostin.
- Ilaria Malanchi
- , Albert Santamaria-Martínez
- & Joerg Huelsken