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Non-invasive classification of microcalcifications with phase-contrast X-ray mammography
X-ray absorption imaging is used for early breast cancer detection but can barely identify the morphology of microcalcifications—a possible indicator of cancer. Wang et al.develop a technique to non-invasively classify different types of microcalcifications and achieve 100% sensitivity on phantom data.
- Zhentian Wang
- , Nik Hauser
- & Marco Stampanoni
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An improved monomeric infrared fluorescent protein for neuronal and tumour brain imaging
Infrared fluorescent proteins offer advantages for deep in vivo imaging thanks to the tissue-penetrating properties of infrared light. Here, Yu et al. design a monomeric infrared fluorescent protein that, when combined with expression of haeme oxygenase in cells, shows improved performance for in vivoimaging of neurons and brain tumours.
- Dan Yu
- , William Clay Gustafson
- & Xiaokun Shu
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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
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Enriched variations in TEKT4 and breast cancer resistance to paclitaxel
Paclitaxel is effective in the treatment of breast cancer but predicting which patients might respond to this drug is of clinical importance. Here, Jiang et al. show that germline mutations in TEKT4, a protein that associates with microtubules, are associated with resistance to paclitaxel therapy.
- Yi-Zhou Jiang
- , Ke-Da Yu
- & Zhi-Ming Shao
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The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis
E3 ligases that attach ubiquitin to proteins destined for proteasomal degradation are regulated by neddylation. In this study, Xie et al. show that the HECT ligase Smurf1, which is a ubiquitin ligase, is also neddylated, and this post-translational modification enhances its ligase activity.
- Ping Xie
- , Minghua Zhang
- & Lingqiang Zhang
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Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency
Hepatocellular carcinoma (HCC) is associated with chronic inflammation, but the genetic basis of the disease remains unclear. Here, the authors report that defects in hepatocyte biliary transporters and subsequent liver inflammation induce genomic alterations that promote HCC in human and mouse.
- Fabio Iannelli
- , Agnese Collino
- & Francesca D. Ciccarelli
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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
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| Open AccessIntegrated exome and transcriptome sequencing reveals ZAK isoform usage in gastric cancer
The genetic basis of gastric cancer, the fourth most common cancer worldwide, remains poorly understood. Here, the authors sequence and analyse the exomes and transcriptomes of primary gastric tumours and cell lines, and identify a ZAK kinase isoform that may have an oncogenic role in gastric cancer.
- Jinfeng Liu
- , Mark McCleland
- & Zemin Zhang
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Protein grafting of p53TAD onto a leucine zipper scaffold generates a potent HDM dual inhibitor
The protein levels of the tumour suppressor p53 can be negatively regulated by HDM2, which is an attractive target for cancer therapy. In this study, Lee et al. graft the transactivation domain of p53 onto a scaffold protein and show that this binds to HDM2 and inhibits cancer cell growth in vitro.
- Jung-Hoon Lee
- , Eunji Kang
- & Jae Il Lee
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| Open AccessWhole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden
Bladder cancer is a complex genetic disease and a common cause of death due to malignancy. Here, the authors carry out whole-genome sequencing of 14 bladder cancers to characterize the genomic landscape of the disease and show that mutational burden is associated with tumour progression in these samples.
- J. -B. Cazier
- , S. R. Rao
- & F. C. Hamdy
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IKKα restoration via EZH2 suppression induces nasopharyngeal carcinoma differentiation
Nasopharyngeal carcinomas often present as undifferentiated tumours. Here, Yan et al. show that reduced expression of IKK via promoter methylation results in the undifferentiated phenotype of the tumours and that treatment with retinoic acid can reverse these features.
- Min Yan
- , Yan Zhang
- & Quentin Liu
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| Open AccessProcessed pseudogenes acquired somatically during cancer development
Germline pseudogenes have an important role in human evolution. Here, the authors analyse sequencing data from 660 cancer samples and find evidence for the formation of somatically acquired pseudogenes, a new class of mutation, which may contribute to cancer development.
- Susanna L. Cooke
- , Adam Shlien
- & Gerrit K.J. Hooijer
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The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes
Proteins involved in epigenetic regulation are frequently mutated in several paediatric cancers. Here, Huether et al.characterize the somatic mutation frequency across 21 paediatric cancer subtypes by sequencing 633 epigenetic genes in over 1,000 tumours; generating a rich data set for investigating epigenetic dysregulation.
- Robert Huether
- , Li Dong
- & James R. Downing
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| Open AccessHarnessing photochemical internalization with dual degradable nanoparticles for combinatorial photo–chemotherapy
Photochemical internalisation is the process by which a laser source activates light sensitive compounds for cellular uptake. Here, the authors combine this technique with photo–chemo degradable polymers for the controlled uptake of chemotherapeutics into cancer cells showing increased cell death.
- George Pasparakis
- , Theodore Manouras
- & Panagiotis Argitis
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| Open AccessUltra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen
The potential of extracellular vesicles (EVs) as cancer biomarkers is substantial. Here, Yoshioka et al. describe a sensitive technique to analyse EVs directly from blood samples of patients with colorectal cancer, highlighting a liquid biopsy technique with cancer-detection possibilities.
- Yusuke Yoshioka
- , Nobuyoshi Kosaka
- & Takahiro Ochiya
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| Open AccessPorphyrin–phospholipid liposomes permeabilized by near-infrared light
The delivery of therapeutics using an external trigger is an attractive route for the improvement of targeted disease treatment. Here, the authors have discovered a porphyrin–phospholipid liposome for light-controlled membrane permeabilization and use the system to deliver an anticancer drug in vivo.
- Kevin A. Carter
- , Shuai Shao
- & Jonathan F. Lovell
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| Open AccessA DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
Defective proteins or functional proteins that are no longer needed can be degraded in the endoplasmic reticulum. In this study, Lopez-Serra et al.show that DERL3, which is involved in protein degradation in the endoplasmic reticulum, is aberrantly silenced in cancer, leading to activation of a glucose transporter and dysregulated glycolysis.
- Paula Lopez-Serra
- , Miguel Marcilla
- & Manel Esteller
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Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer
Light-controlled mechanisms for the delivery of drug molecules to cells is a promising route for non-invasive disease therapy. Here, the authors develop a photosensitive polymeric micelle for light-induced gene transfection and show its effectiveness in vivovia systemic administration.
- Takahiro Nomoto
- , Shigeto Fukushima
- & Kazunori Kataoka
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Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids
Pulmonary carcinoids account for about 2% of pulmonary neoplasms. Here, the authors carry out gene copy number analysis, genome/exome, and transcriptome sequencing of pulmonary carcinoids and identify frequent mutations in chromatin-remodelling genes that can drive tumorigenesis in these tumours.
- Lynnette Fernandez-Cuesta
- , Martin Peifer
- & Roman K. Thomas
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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
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Spontaneous tumour regression in keratoacanthomas is driven by Wnt/retinoic acid signalling cross-talk
Keratoacanthomas are skin tumours that spontaneously regress but the mechanisms leading to regression are unknown. Here, using a mouse chemical carcinogenesis model, the authors show that tumour regression is driven by activation of retinoic acid signalling that induces Wnt inhibition and tumour differentiation.
- Giovanni Zito
- , Ichiko Saotome
- & Valentina Greco
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Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling
Cancer stem cells are a sub-population of tumour cells but how they interact with the tumour microenvironment is unclear. Here, Chen et al.culture lung cancer stem cells with cancer-associated fibroblasts and delineate a signalling pathway between the two cells that helps maintain the cancer stem cell state.
- Wan-Jiun Chen
- , Chao-Chi Ho
- & Pan-Chyr Yang
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Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia
Epigenetic regulators have been proposed to be modulators of chemoresistance in acute lymphoblastic leukaemia. Here, the authors find enrichment of mutations in epigenetic regulators at relapse, including somatic mutations in SETD2.
- Brenton G. Mar
- , Lars B. Bullinger
- & Scott A. Armstrong
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Selective inhibition of BET bromodomain epigenetic signalling interferes with the bone-associated tumour vicious cycle
A major problem in the treatment of bone tumours and metastases is the vicious cycle between bone tumours and resorption. Here, the authors show that treatment with the BET bromodomain inhibitor JQ1 inhibits osteoblast and osteoclast differentiation, and bone tumour development.
- François Lamoureux
- , Marc Baud’huin
- & Benjamin Ory
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| Open AccessLigand substitutions between ruthenium–cymene compounds can control protein versus DNA targeting and anticancer activity
Ruthenium-cymene-based compounds are investigated as potential anticancer drugs. Here, Adhireksan et al.study two ruthenium-containing compounds with varying cytotoxicity and show that differences in ligand structure may explain their activity and binding to different subcellular targets.
- Zenita Adhireksan
- , Gabriela E. Davey
- & Curt A. Davey
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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
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| Open AccessReduced methylation of PFKFB3 in cancer cells shunts glucose towards the pentose phosphate pathway
Haem oxygenase 1 produces carbon monoxide and this byproduct is known to alter cellular signalling. Here, the authors show that carbon monoxide alters the methylation of PFKFB3 in cancer cells resulting in deregulated cellular metabolism and the shunting of glucose into the pentose phosphate pathway.
- Takehiro Yamamoto
- , Naoharu Takano
- & Makoto Suematsu
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Skp2 suppresses apoptosis in Rb1-deficient tumours by limiting E2F1 activity
The pRb target E2F1 possesses contradictory activities in promoting proliferation and apoptosis. Here, the authors define a pRb-Skp2-p27-cyclin A-E2F1 survival pathway that can be disrupted to prevent Rb1-deficient tumorigenesis in the pituitary intermediate lobe.
- Zhonglei Lu
- , Frederick Bauzon
- & Liang Zhu
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2′-OMe-phosphorodithioate-modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity
Short interfering siRNAs—siRNAs—have therapeutic potential in the treatment of disease; however, their delivery to target tissues is difficult. Here, Wu et al. chemically modify siRNAs and show that this improves loading into the siRNA silencing machinery and thus efficacy in eliminating cancer cells in mice.
- Sherry Y. Wu
- , Xianbin Yang
- & Anil K. Sood
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ATP-triggered anticancer drug delivery
Nanoparticles can deliver drugs to tumours but improvements in selectively targeting tumour cells are required. Here, Mo et al. develop nanocarriers that take advantage of high ATP levels in tumour cells and show that these nanoparticles encapsulating the chemotherapeutic doxorubicin can inhibit tumour growth in mice.
- Ran Mo
- , Tianyue Jiang
- & Zhen Gu
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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
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Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue
The effects of genetic variation on DNA methylation patterns are poorly understood. Here, Shi et al.systematically map methylation-quantitative trait loci in lung, breast and kidney tissue to reveal the impact of inherited variation on the human methylome, which also affects cancer risk.
- Jianxin Shi
- , Crystal N. Marconett
- & Maria Teresa Landi
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Bio-barcode gel assay for microRNA
MicroRNA has been identified to play a role in cancer development, thus its detection at low concentrations would be a highly beneficial diagnostic tool. Here, the authors develop a gel-based bio-barcode assay for microRNA detection using DNA-modified gold nanoparticles, with aM limits of detection.
- Hyojin Lee
- , Jeong-Eun Park
- & Jwa-Min Nam
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Telomerase reverse transcriptase promoter mutations in primary cutaneous melanoma
Cutaneous melanoma is an aggressive form of skin cancer. Here, the authors show that mutations in the TERT promoter of 287 primary melanomas are associated with age, Breslow thickness and tumour ulceration and frequently occur at sun-exposed sites.
- Barbara Heidenreich
- , Eduardo Nagore
- & Rajiv Kumar
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Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers
The PI3K pathway that encompasses the tumour suppressor PTEN contributes to tumourigenesis in adult T-cell leukaemia-lymphoma (ATLL). In this study, Nakahata et al. show that PTEN is dephosphorylated by NDRG2, and that loss of NDGR2 in ATLL results in the activation of the PI3K pathway.
- Shingo Nakahata
- , Tomonaga Ichikawa
- & Kazuhiro Morishita
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Genome-wide transcriptome profiling of homologous recombination DNA repair
Defects in the homologous recombination repair of DNA can result in gene mutation and cancer. In this study, Peng et al.identify a gene signature associated with homologous recombination repair deficiency and show that this can be used both to predict repair defects and clinical outcome in cancer patients.
- Guang Peng
- , Curtis Chun-Jen Lin
- & Shiaw-Yih Lin
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| Open AccessThe DUSP26 phosphatase activator adenylate kinase 2 regulates FADD phosphorylation and cell growth
Adenylate kinase 2 can bind to FADD. In this study, Kim et al.show that adenylate kinase 2 is a tumour suppressor and interacts with the phosphatase DUSP6, and this in turn regulates the phosphorylation of FADD.
- Hyunjoo Kim
- , Ho-June Lee
- & Yong-Keun Jung
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| Open AccessInduction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments
Quiescent sub-populations of cells in tumours are resistant to traditional chemotherapeutics and are responsible for tumour recurrence. Here, Zhang et al. identify a compound that kills quiescent tumour cells in solid tumour tissue by inducing mitochondrial dysfunction.
- Xiaonan Zhang
- , Mårten Fryknäs
- & Stig Linder
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| Open AccessIdentification of renin progenitors in the mouse bone marrow that give rise to B-cell leukaemia
Renin cells have traditionally been associated with the kidney where they regulate blood pressure and fluid electrolyte homeostasis. In this study, Belyea et al.describe a renin progenitor in the bone marrow that gives rise to B-cell leukaemia when RBP-J, the final effector of the Notch pathway, is deleted.
- Brian C. Belyea
- , Fang Xu
- & R. Ariel Gomez
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| Open AccessTransdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma
Non-small cell lung cancer manifests as adenocarcinoma and squamous cell carcinoma but tumours of mixed lineage are often found in humans. Here, the authors show that adenocarcinoma can transdifferentiate into squamous cell carcinomas in mice.
- Xiangkun Han
- , Fuming Li
- & Hongbin Ji
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USP11 regulates PML stability to control Notch-induced malignancy in brain tumours
The tumour suppressor PML is regulated by post-translational modification but the mechanism is unclear. Here, the authors show that PML is deubiquitinated and stabilized by USP11, which is in turn negatively regulated by the Notch signalling pathway.
- Hsin-Chieh Wu
- , Yu-Ching Lin
- & Ruey-Hwa Chen
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Gene co-expression network analysis reveals common system-level properties of prognostic genes across cancer types
Many studies provide evidence of genes that are associated with cancer prognosis but a global view of these genes is lacking. Using data from ‘The Cancer Genome Atlas’, Yang et al.investigate the network properties of prognostic genes and show that these genes tend to be within highly interconnected groups but not the most connected nodes in the gene co-expression network.
- Yang Yang
- , Leng Han
- & Han Liang
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RSPO2–LGR5 signaling has tumour-suppressive activity in colorectal cancer
R-spondin 2 has an important role in development but its function in cancer has not been described. In this study, Wu et al. demonstrate that R-spondin 2 is decreased in expression in colorectal cancer and this is associated with promoter methylation and inhibition of Wnt signalling.
- Changjie Wu
- , Sunquan Qiu
- & Xincheng Lu
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SLAP displays tumour suppressor functions in colorectal cancer via destabilization of the SRC substrate EPHA2
SLAP is an adaptor protein that negatively regulates receptor signalling, but its involvement in cancer has not been described. In this study, Naudin et al. demonstrate that SLAP negatively regulates the receptor EphA2 in a Src-dependent manner and is reduced in expression in colorectal cancer.
- Cécile Naudin
- , Audrey Sirvent
- & Serge Roche
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Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer
Cellular metabolism is dysregulated in cancer and may be reflected in differences in the expression of metabolic genes. In this study, the authors find that mitochondrial folate-coupled dehydrogenase is increased in expression in a wide variety of cancers and negatively correlates with breast cancer patient survival.
- Roland Nilsson
- , Mohit Jain
- & Vamsi K. Mootha
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The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumourigenesis
Lgr5 is a protein that is important for the maintenance of intestinal homeostasis. In this study, the authors demonstrate that Lgr5 is required for colorectal cancer development and its expression is regulated by the transcription factor GATA6.
- Shinnosuke Tsuji
- , Yoshihiro Kawasaki
- & Tetsu Akiyama
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Integrated analysis of germline and somatic variants in ovarian cancer
Ovarian cancer is one of the most common cancers in women and has an average 5-year survival of only 43%. Here, Kanchi et al.describe the germline and somatic mutation spectrum in ovarian cancer patients and identify potential risk variants associated with the disease.
- Krishna L. Kanchi
- , Kimberly J. Johnson
- & Li Ding
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Kinase fusions are frequent in Spitz tumours and spitzoid melanomas
Spitzoid neoplasms constitute a spectrum of melanocytic tumours, characterized by distinct clinical, pathological and genetic features. Here, Wiesner et al. show that kinase fusions represent the majority of oncogenic aberrations in spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid melanoma.
- Thomas Wiesner
- , Jie He
- & Boris C. Bastian
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Article
| Open AccessMaspin is not required for embryonic development or tumour suppression
A role for the serpin maspin has been described in both development and cancer. In this study, the authors demonstrate that maspin knockout mice develop normally and that maspin does not function as a tumour suppressor, suggesting that another gene at the maspin locus may be responsible for this activity.
- Sonia S. Y. Teoh
- , Jessica Vieusseux
- & Phillip I. Bird
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