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JournalISSN: 1469-221X

EMBO Reports

About: EMBO Reports is an academic journal. The journal publishes majorly in the area(s): Chromatin & Transcription factor. It has an ISSN identifier of 1469-221X. Over the lifetime, 5123 publication(s) have been published receiving 274086 citation(s).

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Topics: Chromatin, Transcription factor, RNA ...read more
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Open accessJournal ArticleDOI: 10.1038/SJ.EMBOR.7400731
Ann M O'Hara1, Fergus Shanahan1Institutions (1)
01 Jul 2006-EMBO Reports
Abstract: The intestinal microflora is a positive health asset that crucially influences the normal structural and functional development of the mucosal immune system. Mucosal immune responses to resident intestinal microflora require precise control and an immunosensory capacity for distinguishing commensal from pathogenic bacteria. In genetically susceptible individuals, some components of the flora can become a liability and contribute to the pathogenesis of various intestinal disorders, including inflammatory bowel diseases. It follows that manipulation of the flora to enhance the beneficial components represents a promising therapeutic strategy. The flora has a collective metabolic activity equal to a virtual organ within an organ, and the mechanisms underlying the conditioning influence of the bacteria on mucosal homeostasis and immune responses are beginning to be unravelled. An improved understanding of this hidden organ will reveal secrets that are relevant to human health and to several infectious, inflammatory and neoplastic disease processes.

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Topics: Gut flora (60%), Intestinal mucosa (57%), Flora (53%)

2,060 Citations


Open accessJournal ArticleDOI: 10.1038/SJ.EMBOR.7400779
01 Sep 2006-EMBO Reports
Abstract: The efficient functioning of the endoplasmic reticulum (ER) is essential for most cellular activities and survival. Conditions that interfere with ER function lead to the accumulation and aggregation of unfolded proteins. ER transmembrane receptors detect the onset of ER stress and initiate the unfolded protein response (UPR) to restore normal ER function. If the stress is prolonged, or the adaptive response fails, apoptotic cell death ensues. Many studies have focused on how this failure initiates apoptosis, as ER stress-induced apoptosis is implicated in the pathophysiology of several neurodegenerative and cardiovascular diseases. In this review, we examine the role of the molecules that are activated during the UPR in order to identify the molecular switch from the adaptive phase to apoptosis. We discuss how the activation of these molecules leads to the commitment of death and the mechanisms that are responsible for the final demise of the cell.

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1,900 Citations


Open accessJournal ArticleDOI: 10.1038/EMBOR.2008.74
Ulrike Burk1, Joerg Schubert1, Ulrich F. Wellner1, Otto Schmalhofer1  +3 moreInstitutions (2)
01 Jun 2008-EMBO Reports
Abstract: The embryonic programme 'epithelial-mesenchymal transition' (EMT) is thought to promote malignant tumour progression. The transcriptional repressor zinc-finger E-box binding homeobox 1 (ZEB1) is a crucial inducer of EMT in various human tumours, and was recently shown to promote invasion and metastasis of tumour cells. Here, we report that ZEB1 directly suppresses transcription of microRNA-200 family members miR-141 and miR-200c, which strongly activate epithelial differentiation in pancreatic, colorectal and breast cancer cells. Notably, the EMT activators transforming growth factor beta2 and ZEB1 are the predominant targets downregulated by these microRNAs. These results indicate that ZEB1 triggers an microRNA-mediated feedforward loop that stabilizes EMT and promotes invasion of cancer cells. Alternatively, depending on the environmental trigger, this loop might switch and induce epithelial differentiation, and thus explain the strong intratumorous heterogeneity observed in many human cancers.

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1,555 Citations


Open accessJournal ArticleDOI: 10.1093/EMBO-REPORTS/KVE046
01 Mar 2001-EMBO Reports
Abstract: Apoptosis signal‐regulating kinase (ASK) 1 is activated in response to various cytotoxic stresses including TNF, Fas and reactive oxygen species (ROS) such as H2O2, and activates c‐Jun NH2‐terminal kinase (JNK) and p38. However, the roles of JNK and p38 signaling pathways during apoptosis have been controversial. Here we show that by deleting ASK1 in mice, TNF‐ and H2O2‐induced sustained activations of JNK and p38 are lost in ASK1 −/− embryonic fibroblasts, and that ASK1 −/− cells are resistant to TNF‐ and H2O2‐induced apoptosis. TNF‐ but not Fas‐induced apoptosis requires ROS‐dependent activation of ASK1–JNK/p38 pathways. Thus, ASK1 is selectively required for TNF‐ and oxidative stress‐induced sustained activations of JNK/p38 and apoptosis.

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Topics: MAP kinase kinase kinase (58%), p38 mitogen-activated protein kinases (57%), ASK1 (56%) ...read more

1,111 Citations


Open accessJournal ArticleDOI: 10.15252/EMBR.201439246
01 Dec 2014-EMBO Reports
Abstract: The extracellular matrix regulates tissue development and homeostasis, and its dysregulation contributes to neoplastic progression. The extracellular matrix serves not only as the scaffold upon which tissues are organized but provides critical biochemical and biomechanical cues that direct cell growth, survival, migration and differentiation and modulate vascular development and immune function. Thus, while genetic modifications in tumor cells undoubtedly initiate and drive malignancy, cancer progresses within a dynamically evolving extracellular matrix that modulates virtually every behavioral facet of the tumor cells and cancer-associated stromal cells. Hanahan and Weinberg defined the hallmarks of cancer to encompass key biological capabilities that are acquired and essential for the development, growth and dissemination of all human cancers. These capabilities include sustained proliferation, evasion of growth suppression, death resistance, replicative immortality, induced angiogenesis, initiation of invasion, dysregulation of cellular energetics, avoidance of immune destruction and chronic inflammation. Here, we argue that biophysical and biochemical cues from the tumor-associated extracellular matrix influence each of these cancer hallmarks and are therefore critical for malignancy. We suggest that the success of cancer prevention and therapy programs requires an intimate understanding of the reciprocal feedback between the evolving extracellular matrix, the tumor cells and its cancer-associated cellular stroma.

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Topics: The Hallmarks of Cancer (55%), Extracellular matrix (54%), Angiogenesis (52%) ...read more

996 Citations


Performance
Metrics
No. of papers from the Journal in previous years
YearPapers
2021320
2020327
2019250
2018224
2017217
2016188

Top Attributes

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Journal's top 5 most impactful authors

Philip Hunter

188 papers, 1.5K citations

Frank Gannon

59 papers, 795 citations

Howard Wolinsky

40 papers, 429 citations

Holger Breithaupt

37 papers, 307 citations

Vicki Brower

29 papers, 280 citations

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