Abstract:
:The Hedgehog signaling is a determinant pathway for tumor progression. However, while inhibition of the Hedgehog canonical pathway-Patched-Smoothened-Gli-has proved efficient in human tumors with activating mutations in this pathway, recent clinical data have failed to show any benefit in other cancers, even though Sonic Hedgehog (SHH) expression is detected in these cancers. Cell-adhesion molecule-related/down-regulated by Oncogenes (CDON), a positive regulator of skeletal muscle development, was recently identified as a receptor for SHH. We show here that CDON behaves as a SHH dependence receptor: it actively triggers apoptosis in the absence of SHH. The pro-apoptotic activity of unbound CDON requires a proteolytic cleavage in its intracellular domain, allowing the recruitment and activation of caspase-9. We show that by inducing apoptosis in settings of SHH limitation, CDON expression constrains tumor progression, and as such, decreased CDON expression observed in a large fraction of human colorectal cancer is associated in mice with intestinal tumor progression. Reciprocally, we propose that the SHH expression, detected in human cancers and previously considered as a mechanism for activation of the canonical pathway in an autocrine or paracrine manner, actually provides a selective tumor growth advantage by blocking CDON-induced apoptosis. In support of this notion, we present the preclinical demonstration that interference with the SHH-CDON interaction triggers a CDON-dependent apoptosis in vitro and tumor growth inhibition in vivo. The latter observation qualifies CDON as a relevant alternative target for anticancer therapy in SHH-expressing tumors.
journal_name
PLoS Bioljournal_title
PLoS biologyauthors
Delloye-Bourgeois C,Gibert B,Rama N,Delcros JG,Gadot N,Scoazec JY,Krauss R,Bernet A,Mehlen Pdoi
10.1371/journal.pbio.1001623subject
Has Abstractpub_date
2013-01-01 00:00:00pages
e1001623issue
8eissn
1544-9173issn
1545-7885pii
PBIOLOGY-D-13-00680journal_volume
11pub_type
杂志文章相关文献
PLOS BIOLOGY文献大全abstract::Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public mone...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.2000314
更新日期:2016-09-29 00:00:00
abstract::Courtship is a widespread behavior in which one gender conveys to the other a series of cues about their species identity, gender, and suitability as mates. In many species, females decode these male displays and either accept or reject them. Despite the fact that courtship has been investigated for a long time, the g...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001964
更新日期:2014-10-07 00:00:00
abstract::The transcription rate of a gene is often controlled by several regulators that bind specific sites in the gene's cis-regulatory region. The combined effect of these regulators is described by a cis-regulatory input function. What determines the form of an input function, and how variable is it with respect to mutatio...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0040045
更新日期:2006-04-01 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pbio.1002436.]. ...
journal_title:PLoS biology
pub_type: 已发布勘误
doi:10.1371/journal.pbio.1002494
更新日期:2016-06-08 00:00:00
abstract::The fate of neural progenitor cells (NPCs) during corticogenesis is determined by a complex interplay of genetic or epigenetic components, but the underlying mechanism is incompletely understood. Here, we demonstrate that Suppressor of Mek null (Smek) interact with methyl-CpG-binding domain 3 (Mbd3) and the complex pl...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.2001220
更新日期:2017-05-03 00:00:00
abstract::Do malaria parasites enhance the attractiveness of humans to the parasite's vector? As such manipulation would have important implications for the epidemiology of the disease, the question has been debated for many years. To investigate the issue in a semi-natural situation, we assayed the attractiveness of 12 groups ...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0030298
更新日期:2005-09-01 00:00:00
abstract::The survival of animals depends critically on prioritizing responses to motivationally salient stimuli. While it is generally believed that motivational salience increases decision speed, the quantitative relationship between motivational salience and decision speed, measured by reaction time (RT), remains unclear. He...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001811
更新日期:2014-03-18 00:00:00
abstract::From early dinosaurs with as many as nine wrist bones, modern birds evolved to develop only four ossifications. Their identity is uncertain, with different labels used in palaeontology and developmental biology. We examined embryos of several species and studied chicken embryos in detail through a new technique allowi...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001957
更新日期:2014-09-30 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pbio.3000478.]. ...
journal_title:PLoS biology
pub_type: 已发布勘误
doi:10.1371/journal.pbio.3000568
更新日期:2019-11-13 00:00:00
abstract::Tumors develop through multiple stages, implicating multiple effectors, but the tools to assess how candidate genes contribute to stepwise tumor progression have been limited. We have developed a novel system in which progression of phenotypes in a mouse model of pancreatic islet cell tumorigenesis can be used to meas...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0050276
更新日期:2007-10-16 00:00:00
abstract::Phenotypic heterogeneity can confer clonal groups of organisms with new functionality. A paradigmatic example is the bistable expression of virulence genes in Salmonella typhimurium, which leads to phenotypically virulent and phenotypically avirulent subpopulations. The two subpopulations have been shown to divide lab...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001928
更新日期:2014-08-19 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pbio.2004814.]. ...
journal_title:PLoS biology
pub_type: 杂志文章,已发布勘误
doi:10.1371/journal.pbio.1002619
更新日期:2018-01-25 00:00:00
abstract::Rodent whisker input consists of dense microvibration sequences that are often temporally integrated for perceptual discrimination. Whether primary somatosensory cortex (S1) participates in temporal integration is unknown. We trained rats to discriminate whisker impulse sequences that varied in single-impulse kinemati...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1002549
更新日期:2016-08-30 00:00:00
abstract::RNA-mediated interference (RNAi) is a method to inhibit gene function by introduction of double-stranded RNA (dsRNA). Recently, an RNAi library was constructed that consists of bacterial clones expressing dsRNA, corresponding to nearly 90% of the 19,427 predicted genes of C. elegans. Feeding of this RNAi library to th...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0000012
更新日期:2003-10-01 00:00:00
abstract::The Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were developed to address the lack of reproducibility in biomedical animal studies and improve the communication of research findings. While intended to guide the preparation of peer-reviewed manuscripts, the principles of transparent reporting ...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1002151
更新日期:2015-05-20 00:00:00
abstract::The Hippo pathway directs cell differentiation during organogenesis, in part by restricting proliferation. How Hippo signaling maintains a proliferation-differentiation balance in developing tissues via distinct molecular targets is only beginning to be understood. Our study makes the unexpected finding that Hippo sup...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.3000382
更新日期:2019-07-19 00:00:00
abstract::Organisms evolve two routes to surviving infections-they can resist pathogen growth (resistance) and they can endure the pathogenesis of infection (tolerance). The sum of these two properties together defines the defensive capabilities of the host. Typically, studies of animal defenses focus on either understanding re...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0060305
更新日期:2008-12-09 00:00:00
abstract::We used a class of designed peptide detergents to stabilize photosystem I (PS-I) upon extended drying under N2 on a gold-coated-Ni-NTA glass surface. PS-I is a chlorophyll-containing membrane protein complex that is the primary reducer of ferredoxin and the electron acceptor of plastocyanin. We isolated the complex fr...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0030230
更新日期:2005-07-01 00:00:00
abstract::Differentiated T helper (Th) cell lineages are thought to emerge from alternative cell fate decisions. However, recent studies indicated that differentiated Th cells can adopt mixed phenotypes during secondary immunological challenges. Here we show that natural primary immune responses against parasites generate bifun...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001633
更新日期:2013-01-01 00:00:00
abstract::Global warming is significantly altering arctic marine ecosystems. Specifically, the precipitous loss of sea ice is creating a dichotomy between ice-dependent polar bears and pinnipeds that are losing habitat and some cetaceans that are gaining habitat. While final outcomes are hard to predict for the many and varied ...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.2006708
更新日期:2018-10-09 00:00:00
abstract::Protein modifications play a major role for most biological processes in living organisms. Amino-terminal acetylation of proteins is a common modification found throughout the tree of life: the N-terminus of a nascent polypeptide chain becomes co-translationally acetylated, often after the removal of the initiating me...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1000236
更新日期:2009-11-01 00:00:00
abstract::Kabuki Syndrome patients have a spectrum of congenital disorders, including congenital heart defects, the primary determinant of mortality. Seventy percent of Kabuki Syndrome patients have mutations in the histone methyl-transferase KMT2D. However, the underlying mechanisms that drive these congenital disorders are un...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.3000087
更新日期:2019-09-03 00:00:00
abstract::Hox transcription factors control a number of developmental processes with the help of the PBC class proteins. In vitro analyses have established that the formation of Hox/PBC complexes relies on a short conserved Hox protein motif called the hexapeptide (HX). This paradigm is at the basis of the vast majority of expe...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001351
更新日期:2012-01-01 00:00:00
abstract::Pollen tube (PT) reception in flowering plants describes the crosstalk between the male and female gametophytes upon PT arrival at the synergid cells of the ovule. It leads to PT growth arrest, rupture, and sperm cell release, and is thus essential to ensure double fertilization. Here, we describe TURAN (TUN) and EVAN...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1002139
更新日期:2015-04-28 00:00:00
abstract::DEAD-box helicase proteins accelerate folding and rearrangements of highly structured RNAs and RNA-protein complexes (RNPs) in many essential cellular processes. Although DEAD-box proteins have been shown to use ATP to unwind short RNA helices, it is not known how they disrupt RNA tertiary structure. Here, we use sing...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001981
更新日期:2014-10-28 00:00:00
abstract::Pheromones form an essential chemical language of intraspecific communication in many animals. How olfactory systems recognize pheromonal signals with both sensitivity and specificity is not well understood. An important in vivo paradigm for this process is the detection mechanism of the sex pheromone (Z)-11-octadecen...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001546
更新日期:2013-01-01 00:00:00
abstract::In a world beset by attempts to undermine scientific evidence and evidence-based policy, we emphasize their important role in helping humanity rise to the challenges of our time. ...
journal_title:PLoS biology
pub_type: 社论
doi:10.1371/journal.pbio.3000992
更新日期:2020-10-22 00:00:00
abstract::The evolution of altruism is a fundamental and enduring puzzle in biology. In a seminal paper Hamilton showed that altruism can be selected for when rb - c > 0, where c is the fitness cost to the altruist, b is the fitness benefit to the beneficiary, and r is their genetic relatedness. While many studies have provided...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1000615
更新日期:2011-05-01 00:00:00
abstract::Calorie restriction slows aging and increases life span in many organisms. In yeast, a mechanistic explanation has been proposed whereby calorie restriction slows aging by activating Sir2. Here we report the identification of a Sir2-independent pathway responsible for a majority of the longevity benefit associated wit...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0020296
更新日期:2004-09-01 00:00:00
abstract::We have obtained precatalytic (enzyme-substrate complex) and postcatalytic (enzyme-product complex) crystal structures of an active full-length hammerhead RNA that cleaves in the crystal. Using the natural satellite tobacco ringspot virus hammerhead RNA sequence, the self-cleavage reaction was modulated by substitutin...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0060234
更新日期:2008-09-30 00:00:00