Featured
-
-
Article
| Open AccessBrain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier
A key event during metastasis to the brain is the migration of cancer cells through the blood–brain barrier (BBB). Here the authors show that cancer-cell-derived extracellular vesicles promote metastasis by promoting BBB breaching.
- Naoomi Tominaga
- , Nobuyoshi Kosaka
- & Takahiro Ochiya
-
Article
| Open AccessTracking the origins and drivers of subclonal metastatic expansion in prostate cancer
Primary prostate tumours are known to be genetically heterogeneous and clonal selection has the potential to drive metastasis. Here Hong et al. show that the acquisition of TP53 mutations is linked to clonal expansion and metastatic progression to lethality.
- Matthew K.H. Hong
- , Geoff Macintyre
- & Christopher M. Hovens
-
Article
| Open AccessSensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo
Surgical removal of the metastases remains a life-extending approach to ovarian cancer, but the nodules are difficult to detect. Here the authors show that a new cell-permeable probe for β-galactosidase can sensitively and specifically detect peritoneal metastases in mouse models of ovarian cancer.
- Daisuke Asanuma
- , Masayo Sakabe
- & Yasuteru Urano
-
Article |
Off-target-free gene delivery by affinity-purified receptor-targeted viral vectors
The clinical use of adeno-associated virus vectors (AAVs) has been limited by the lack of transduction specificity. Here the authors show that receptor-targeted, affinity-tagged, and purified AVVs reach tumours in mouse models with high selectivity and efficiency, outperforming therapeutic antibodies.
- Robert C. Münch
- , Anke Muth
- & Christian J. Buchholz
-
Article |
NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes
Tumour cells disseminated from the primary tumour can remain dormant for years before initiating metastases. Here Sosa et al.show that the orphan nuclear receptor NR2F1 can be induced by bone marrow cues and by epigenetic drugs to promote quiescence and tumour cell dormancy in several cancer types.
- Maria Soledad Sosa
- , Falguni Parikh
- & Julio A. Aguirre-Ghiso
-
Article
| Open AccessUCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1α
When stabilized, HIF-1 can activate adaptation to hypoxia and metastasis. Here the authors show that upregulation of Ubiquitin C-terminal hydrolase-L1 in human cancers promotes metastasis and correlates with poor prognosis because of its role in opposing ubiquitin-mediated degradation of HIF-1.
- Yoko Goto
- , Lihua Zeng
- & Hiroshi Harada
-
Article |
The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors
The epigenetic modifier EZH2 is highly expressed in melanoma but its role in cancer initiation and progression is still unclear. Here the authors use mouse models and human cell lines to show that EZH2 has an essential role in melanoma progression and metastasis, thus highlighting its potential as a therapeutic target.
- Daniel Zingg
- , Julien Debbache
- & Lukas Sommer
-
Article
| Open AccessGlucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B
Glucocorticoids show promise for the treatment of ovarian cancer. Here the authors show that glucocorticoids transcriptionally induce the tumour suppressor miR-708, which is downregulated in ovarian cancer, especially in late stages and metastatic tumours.
- Kai-Ti Lin
- , Yu-Ming Yeh
- & Lu-Hai Wang
-
Article |
Enrichment of CD56dimKIR+CD57+ highly cytotoxic NK cells in tumour-infiltrated lymph nodes of melanoma patients
The role of NK cells in tumour lymphatics is poorly understood. Here, the authors show that the tumour cell-infiltrated lymph nodes of melanoma patients have an altered cytokine milieu and contain an expanded population of NK cells with high tumour-cytotoxic activity.
- Talib Hassan Ali
- , Simona Pisanti
- & Ennio Carbone
-
Article |
Different thresholds of ZEB1 are required for Ras-mediated tumour initiation and metastasis
The transcription factor ZEB1 has been implicated in different steps of the metastatic cascade. Here the authors show that heterozygous loss of ZEB1in a K-Ras-driven mouse model of lung cancer inhibits progression from lung adenomas to adenocarcinomas.
- Yongqing Liu
- , Xiaoqin Lu
- & Douglas C. Dean
-
Article |
RHOA inactivation enhances Wnt signalling and promotes colorectal cancer
The small GTPase RhoA has oncogenic effects in several cancer types. Here the authors show that loss of RhoA accelerates colon cancer progression by promoting accumulation of nuclear ß-catenin, resulting in enhanced proliferation and invasion mediated by the Wnt signalling pathway in human and murine colon cancer cells.
- Paulo Rodrigues
- , Irati Macaya
- & Diego Arango
-
Article |
BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10
BRMS1, a component of the Sin3A–HDAC repressor complex, blocks invasion and migration of breast cancer cells. Here the authors show that BRMS1-like (BRMS1L) inhibits breast cancer metastasis by blocking epithelial to mesenchymal transition through transcriptional suppression of the FZD10 receptor for Wnt ligands.
- Chang Gong
- , Shaohua Qu
- & Erwei Song
-
Article |
Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein
Factors affecting the fate of disseminating tumour cells in the circulation play a critical role in metastasis. Here the authors show that TLR4 on platelets promotes their adhesion to tumour cells and enhances metastasis.
- Le-Xing Yu
- , Lei Yan
- & Hong-Yang Wang
-
Article |
Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression
Tumour-infiltrating lymphocytes (TILs) can be suppressed by the tumour, but how this occurs is not clear. Here the authors show that the miR-200 family, which suppresses epithelial–mesenchymal transition, also targets tumour cell PD-L1 and thereby intratumoral immunosuppression and metastasis.
- Limo Chen
- , Don L. Gibbons
- & F. Xiao-Feng Qin
-
Article
| Open AccessConcomitant Notch activation and p53 deletion trigger epithelial-to-mesenchymal transition and metastasis in mouse gut
Metastasizing tumour cells undergo epithelial-to-mesenchymal transition. Using both bioinformatic and in vivo approaches, Chanrion et al.identify combined Notch activation and p53 inactivation as a potent inducer of this transition, and apply this to create a highly metastatic tumour model in mice.
- Maia Chanrion
- , Inna Kuperstein
- & Sylvie Robine
-
Article |
Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential
The prognostic significance of stromal cells in ovarian cancer has not been explored. Here the authors show that stromal microfibrillar-associated protein 5 (MFAP5) drives metastasis of ovarian cancer and represents a new a prognostic marker related to decreased survival.
- Cecilia S. Leung
- , Tsz-Lun Yeung
- & Samuel C. Mok
-
Article |
Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis
Focal adhesion kinase (FAK) is frequently overexpressed in solid tumours. Here Batista et al.show that loss of FAK skews hematopoietic progenitors toward myeloid differentiation and promotes metastases, warning against the use of FAK inhibitors in anticancer therapies.
- Silvia Batista
- , Eleni Maniati
- & Kairbaan Hodivala-Dilke
-
Article |
TNFR1 mediates TNF-α-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling
TNF-α signalling regulates a range of pathophysiological functions including tumour growth, but its role in lymphatic metastasis is unclear. Here the authors show that TNF-α signalling stimulates lymphatic endothelial cell activity, lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling.
- Hong Ji
- , Renhai Cao
- & Yihai Cao
-
Article |
Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumour metastasis
Rab-controlled trafficking pathways have been implicated in tumourigenesis. Here the authors show that Rab37 suppresses metastasis by regulating the exocytosis of tissue inhibitor of metalloproteinase 1 to repress matrix metalloproteinase 9 and represents a novel prognostic marker for lung cancer.
- Chung-Han Tsai
- , Hung-Chi Cheng
- & Yi-Ching Wang
-
Article |
Breast cancer cells condition lymphatic endothelial cells within pre-metastatic niches to promote metastasis
Metastases are known to preferentially spread through the lymphatic vessels. Here the authors uncover a self-reinforcing paracrine loop between breast cancer cells and lymphatic endothelial cells, which promotes seeding of cancer cells and angiogenesis in pre-metastatic niches but can be effectively blocked by repurposed therapeutic agents.
- Esak Lee
- , Elana J. Fertig
- & Aleksander S. Popel
-
Article |
Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis
Tumour angiogenesis is critical for tumour growth and metastasis but the mechanisms that promote the growth of new blood vessels by tumours are not completely clear. Here the authors show that overexpression of the transcription factor Twist1 in certain tumour cells can lead them to differentiate into endothelial cells.
- Hsiao-Fan Chen
- , Chi-Hung Huang
- & Kou-Juey Wu
-
Article |
AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion
Loss of cell polarity is frequently observed in metastatic tumours. Mojallal et al.show that this loss is associated with expression of the scaffold protein AmotL2 in human tumours, and reveal that AmotL2 disrupts the transport of polarity complexes to the plasma membrane following its induction by hypoxia.
- Mahdi Mojallal
- , Yujuan Zheng
- & Lars Holmgren
-
Article
| Open AccessClathrin light chains are required for the gyrating-clathrin recycling pathway and thereby promote cell migration
Clathrin light chain (CLC) subunits are dispensable for clathrin-mediated endocytosis of a number of cargoes. Majeed et al. report that CLCs are however required for gyrating-clathrin-dependent recycling of inactive β1-integrins, the absence of which impairs cell migration.
- Sophia R. Majeed
- , Lavanya Vasudevan
- & Frances M. Brodsky
-
Article |
Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease
Ras family members have critical roles in many types of tumours but the role of R-Ras2 in cancer is unclear. Here the authors show that R-Ras2 is important in both the formation of breast primary tumours and metastasis to the lung.
- Romain M. Larive
- , Giulia Moriggi
- & Xosé R. Bustelo
-
Article |
S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells
The cell membrane of metastatic cells is exposed to a variety of physical and chemical stresses. Here, Jaiswal et al. show that S100A11, which is increased in expression in several cancers, is required to promote repair of cell membrane damage in invasive breast cancer cells in vitro.
- Jyoti K. Jaiswal
- , Stine P. Lauritzen
- & Jesper Nylandsted
-
Article |
Lymph node-independent liver metastasis in a model of metastatic colorectal cancer
It remains unclear whether colorectal cancer metastases in the liver arise from intermediate metastases in the lymph nodes or directly from the primary tumour. Enquist et al.demonstrate lymph node-independent metastasis using a mouse model in which tumours are transplanted directly onto the luminal surface of the colon.
- Ida B. Enquist
- , Zinaida Good
- & Kevin G. Leong
-
Article |
MTSS1 is a metastasis driver in a subset of human melanomas
Complex genomic alterations segregate melanoma into different molecular subsets, but for most subsets it is unclear whether they drive a distinct clinical behaviour. Here, the authors use gene-expression data from melanoma patients to search for outlier genes that correlate with survival and identify that MTSS1 is associated with metastasis.
- Kirsten D. Mertz
- , Gaurav Pathria
- & Stephan N. Wagner
-
Article |
Nuclear receptor NR4A1 promotes breast cancer invasion and metastasis by activating TGF-β signalling
The TGF-β signalling pathway promotes cancer progression in late stage breast cancer, but how the pathway is activated is not always clear. In this study, Zhou et al.identify that the expression of nuclear receptor NR4A1 is induced by inflammation and is an activator of TGF-β-induced metastasis.
- FangFang Zhou
- , Yvette Drabsch
- & Peter ten Dijke
-
Article |
MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1
Lung cancers have a high potential to become metastatic, which is a major cause of treatment failure. Here, the authors identify a microRNA that is upregulated in non-small-cell lung cancer and is associated with Hippo pathway modulation metastasis and poor clinical outcome.
- Ching-Wen Lin
- , Yih-Leong Chang
- & Pan-Chyr Yang
-
Article
| Open AccessPrimary tumours modulate innate immune signalling to create pre-metastatic vascular hyperpermeability foci
Tumours are thought to pave the way for metastases to distant organs by secreting factors create regions of increased vascular permeability. Hiratsuka et al.identify innate immune pathways that underlie this process in the pre-metastatic lungs of tumour-bearing mice and patients.
- Sachie Hiratsuka
- , Sachie Ishibashi
- & Yoshiro Maru
-
Article |
Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis
Cancer-associated fibroblasts promote tumour growth and metastasis by secreting signalling molecules. Jung and colleagues show that prostate cancer cells secrete CXC chemokine ligand 16, which recruits mesenchymal stem cells and converts them into cancer-associated fibroblasts.
- Younghun Jung
- , Jin Koo Kim
- & Russell S. Taichman
-
Article
| Open AccessAssociation between Gαi2 and ELMO1/Dock180 connects chemokine signalling with Rac activation and metastasis
Chemokines promote breast cancer metastasis by stimulating re-organization of the actin cytoskeleton. Li et al. identify the human engulfment and cell motility protein ELMO1 as an intermediary between chemokine-dependent Gαi2 signalling and small GTPase signalling mediated by Rac.
- Hongyan Li
- , Lei Yang
- & Ning Zhang
-
Article |
Src activation by β-adrenoreceptors is a key switch for tumour metastasis
The neurotransmitter noradrenaline can regulate cellular processes that contribute to cancer progression, but the underlying mechanisms remain largely unknown. Here the authors identify Src as a key mediator of noradrenaline signalling networks in tumour metastasis.
- Guillermo N. Armaiz-Pena
- , Julie K. Allen
- & Anil K. Sood
-
Article |
Interaction between p68 RNA helicase and Ca2+-calmodulin promotes cell migration and metastasis
Cell migration requires motor protein-driven delivery of proteins to the leading edge. This study shows that p68 RNA helicase behaves as a microtubule-based motor upon binding calmodulin, and that blocking this interaction inhibits cancer cell metastasis.
- Haizhen Wang
- , Xueliang Gao
- & Zhi-Ren Liu
-
Article |
The metastasis-promoting S100A4 protein confers neuroprotection in brain injury
Multifunctional S100 proteins are upregulated in brain injury, but their role in neurodegeneration is not clear. Dmytriyeva and colleagues study in vivomodels of brain trauma and find that the S100A4 protein and its peptide mimetics protect neurons via the interleukin-10 receptor and the Janus kinase (JAK)/STAT pathway.
- Oksana Dmytriyeva
- , Stanislava Pankratova
- & Darya Kiryushko
-
Article |
A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis
Interactions of cells with extracellular matrix are important in normal physiology and cancer metastasis. Here, an extracellular matrix molecule array is developed and used to show that conserved changes in adhesive properties are associated with metastasis, including binding to fibronectin in combination with galectin-3, galectin-8 or laminin.
- Nathan E. Reticker-Flynn
- , David F. Braga Malta
- & Sangeeta N. Bhatia
-
Article |
Lysine methylation of VCP by a member of a novel human protein methyltransferase family
Methyltransferases modify cellular proteins in addition to DNA and histones. These authors identify a new family of lysine-specific methyltransferases and show that a member of this family, which is associated with tumour metastasis, methylates the ATP-dependent protein chaperone VCP/p97.
- Stefan Kernstock
- , Erna Davydova
- & Pål Ø. Falnes
-
Article |
Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell
CD44 is a cell surface protein that is a marker for stem cell-like cancer cells and has a role in invasion and metastasis. Here, epithelial splicing regulatory protein 1 is shown to generate a CD44 variant protein that enhances metastasis in a mouse model and protects cells from oxidative stress.
- Toshifumi Yae
- , Kenji Tsuchihashi
- & Osamu Nagano
-
Article |
EphB3 suppresses non-small-cell lung cancer metastasis via a PP2A/RACK1/Akt signalling complex
The role of ephrin receptors in tumour development and progression has remained controversial. Liet al. show that kinase activation of ephrin-B3 inhibits non-small-cell lung cancer migration both in vitro and in vivo, which depends on a novel interacting partner, RACK 1, in a ternary complex with PP2A and Akt.
- Guo Li
- , Xiao-Dan Ji
- & Dong Xie
-
Article
| Open AccessGenome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis
microRNAs are known to be deregulated in cancer. Using a screen for microRNAs that alter cell migration, Zhanget al. show that mir-23b blocks cell migration in vitro and in vivoand is reduced in expression in human colon cancer, suggesting a therapeutic potential for this microRNA.
- Hanshuo Zhang
- , Yang Hao
- & Jianzhong Jeff Xi
-
Article |
P-Rex1 is required for efficient melanoblast migration and melanoma metastasis
The processes that regulate melanoblast migration during development are also thought to be involved in melanoma metastasis. Here, Prex1 null mice are shown to have a melanoblast migration defect and, when crossed to a mouse model of melanoma, are resistant to metastasis, suggesting a role for Prex1 in metastatic melanoma.
- Colin R. Lindsay
- , Samuel Lawn
- & Owen J. Sansom
-
Article
| Open AccessThe deubiquitinating enzyme USP17 is essential for GTPase subcellular localization and cell motility
Deubiquitinating enzymes are involved in multiple cellular processes, including cell viability. The authors reveal a role for the deubiquitinating enzyme, USP17, in the migration of cells in response to chemokines and show that USP17 is required for the relocalization of GTPases involved in cell motility.
- Michelle de la Vega
- , Alyson A. Kelvin
- & James A. Johnston
-
Article
| Open AccessIdentification of high-quality cancer prognostic markers and metastasis network modules
There has been great interest in attempting to identify gene expression signatures that predict cancer survival. In this study a new algorithm is developed to analyse gene expression datasets that accurately classify both ER+ and ER− breast cancers into low- and high-risk groups.
- Jie Li
- , Anne E.G. Lenferink
- & Edwin Wang