Abstract:
:Communication between neoplastic cells and cells of their microenvironment is critical to cancer progression. To investigate the role of cytoneme-mediated signaling as a mechanism for distributing growth factor signaling proteins between tumor and tumor-associated cells, we analyzed EGFR and RET Drosophila tumor models and tested several genetic loss-of-function conditions that impair cytoneme-mediated signaling. Neuroglian, capricious, Irk2, SCAR, and diaphanous are genes that cytonemes require during normal development. Neuroglian and Capricious are cell adhesion proteins, Irk2 is a potassium channel, and SCAR and Diaphanous are actin-binding proteins, and the only process to which they are known to contribute jointly is cytoneme-mediated signaling. We observed that diminished function of any one of these genes suppressed tumor growth and increased organism survival. We also noted that EGFR-expressing tumor discs have abnormally extensive tracheation (respiratory tubes) and ectopically express Branchless (Bnl, a FGF) and FGFR. Bnl is a known inducer of tracheation that signals by a cytoneme-mediated process in other contexts, and we determined that exogenous over-expression of dominant negative FGFR suppressed tumor growth. Our results are consistent with the idea that cytonemes move signaling proteins between tumor and stromal cells and that cytoneme-mediated signaling is required for tumor growth and malignancy.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Fereres S,Hatori R,Hatori M,Kornberg TBdoi
10.1371/journal.pgen.1008415subject
Has Abstractpub_date
2019-09-30 00:00:00pages
e1008415issue
9eissn
1553-7390issn
1553-7404pii
PGENETICS-D-19-01310journal_volume
15pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Human growth has an estimated heritability of about 80%-90%. Nevertheless, the underlying cause of shortness of stature remains unknown in the majority of individuals. Genome-wide association studies (GWAS) showed that both common single nucleotide polymorphisms and copy number variants (CNVs) contribute to height var...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003365
更新日期:2013-01-01 00:00:00
abstract::The cell envelope of Gram-negative bacteria is a formidable barrier that is difficult for antimicrobial drugs to penetrate. Thus, the list of treatments effective against these organisms is small and with the rise of new resistance mechanisms is shrinking rapidly. New therapies to treat Gram-negative bacterial infecti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004056
更新日期:2014-01-01 00:00:00
abstract::The Caenorhabditis elegans class A and B synthetic multivulva (synMuv) genes redundantly antagonize an EGF/Ras pathway to prevent ectopic vulval induction. We identify a class A synMuv mutation in the promoter of the lin-3 EGF gene, establishing that lin-3 is the key biological target of the class A synMuv genes in vu...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002418
更新日期:2011-12-01 00:00:00
abstract::Detailed information about stage-specific changes in gene expression is crucial for the understanding of the gene regulatory networks underlying development. Here, we describe the global gene expression dynamics during early flower development, a key process in the life cycle of a plant, during which floral patterning...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020117.eor
更新日期:2006-07-01 00:00:00
abstract::The PTEN-induced kinase 1 (PINK1) is a mitochondrial kinase, and pink1 mutations cause early onset Parkinson's disease (PD) in humans. Loss of pink1 in Drosophila leads to defects in mitochondrial function, and genetic data suggest that another PD-related gene product, Parkin, acts with pink1 to regulate the clearance...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003478
更新日期:2013-04-01 00:00:00
abstract::Transcription factors are grouped into families based on sequence similarity within functional domains, particularly DNA-binding domains. The Specificity proteins Sp1, Sp2 and Sp3 are paradigmatic of closely related transcription factors. They share amino-terminal glutamine-rich regions and a conserved carboxy-termina...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005102
更新日期:2015-03-20 00:00:00
abstract::Global climate change, increasingly erratic weather and a burgeoning global population are significant threats to the sustainability of future crop production. There is an urgent need for the development of robust measures that enable crops to withstand the uncertainty of climate change whilst still producing maximum ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005705
更新日期:2015-12-03 00:00:00
abstract::Reproductive proteins are among the fastest evolving in the proteome, often due to the consequences of positive selection, and their rapid evolution is frequently attributed to a coevolutionary process between interacting female and male proteins. Such a process could leave characteristic signatures at coevolving gene...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000570
更新日期:2009-07-01 00:00:00
abstract::Changes in gene regulatory circuits often give rise to phenotypic differences among closely related organisms. In bacteria, these changes can result from alterations in the ancestral genome and/or be brought about by genes acquired by horizontal transfer. Here, we identify an allele of the ancestral transcription fact...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003060
更新日期:2012-01-01 00:00:00
abstract::Numerous studies of human populations in Europe and Asia have revealed a concordance between their extant genetic structure and the prevailing regional pattern of geography and language. For native South Americans, however, such evidence has been lacking so far. Therefore, we examined the relationship between Y-chromo...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003460
更新日期:2013-04-01 00:00:00
abstract::Endoplasmic reticulum (ER) stress activates the Unfolded Protein Response, a compensatory signaling response that is mediated by the IRE-1, PERK/PEK-1, and ATF-6 pathways in metazoans. Genetic studies have implicated roles for UPR signaling in animal development and disease, but the function of the UPR under physiolog...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002391
更新日期:2011-11-01 00:00:00
abstract::The molecular mechanisms of animal cell osmoregulation are poorly understood. Genetic studies of osmoregulation in yeast have identified mucin-like proteins as critical regulators of osmosensitive signaling and gene expression. Whether mucins play similar roles in higher organisms is not known. Here, we show that muta...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001267
更新日期:2011-01-06 00:00:00
abstract::Mating-type switching is a complex mechanism that promotes sexual reproduction in Saccharomycotina. In the model species Saccharomyces cerevisiae, mating-type switching is initiated by the Ho endonuclease that performs a site-specific double-strand break (DSB) at MAT, repaired by homologous recombination (HR) using on...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008627
更新日期:2020-10-15 00:00:00
abstract::AMP-activated protein kinase (AMPK) is an evolutionarily conserved master regulator of metabolism and a therapeutic target in type 2 diabetes. As an energy sensor, AMPK activity is responsive to both metabolic inputs, for instance the ratio of AMP to ATP, and numerous hormonal cues. As in mammals, each of two genes, a...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004394
更新日期:2014-06-12 00:00:00
abstract::In the enterobacterial species Escherichia coli and Salmonella enterica, expression of horizontally acquired genes with a higher than average AT content is repressed by the nucleoid-associated protein H-NS. A classical example of an H-NS-repressed locus is the bgl (aryl-beta,D-glucoside) operon of E. coli. This locus ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000405
更新日期:2009-03-01 00:00:00
abstract::Complex traits are known to be influenced by a combination of environmental factors and rare and common genetic variants. However, detection of such multivariate associations can be compromised by low statistical power and confounding by population structure. Linear mixed effects models (LMM) can account for correlati...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008766
更新日期:2020-05-04 00:00:00
abstract::Akt represents a nodal point between the Insulin receptor and TOR signaling, and its activation by phosphorylation controls cell proliferation, cell size, and metabolism. The activity of Akt must be carefully balanced, as increased Akt signaling is frequently associated with cancer and as insufficient Akt signaling is...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000990
更新日期:2010-06-17 00:00:00
abstract::Mutants of trt-1, the Caenorhabditis elegans telomerase reverse transcriptase, reproduce normally for several generations but eventually become sterile as a consequence of telomere erosion and end-to-end chromosome fusions. Telomere erosion and uncapping do not cause an increase in apoptosis in the germlines of trt-1 ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020018
更新日期:2006-02-01 00:00:00
abstract::Heterozygous mutations in the PRPF31 gene cause autosomal dominant retinitis pigmentosa (adRP), a hereditary disorder leading to progressive blindness. In some cases, such mutations display incomplete penetrance, implying that certain carriers develop retinal degeneration while others have no symptoms at all. Asymptom...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003040
更新日期:2012-01-01 00:00:00
abstract::70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70's in yeast, Ssa1-4, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and acc...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008951
更新日期:2021-01-11 00:00:00
abstract::Signaling pathways enable cells to sense and respond to their environment. Many cellular signaling strategies are conserved from fungi to humans, yet their activity and phenotypic consequences can vary extensively among individuals within a species. A systematic assessment of the impact of naturally occurring genetic ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004913
更新日期:2015-01-08 00:00:00
abstract::Type-III protein secretion systems are utilized by gram-negative pathogens to secrete building blocks of the bacterial flagellum, virulence effectors from the cytoplasm into host cells, and structural subunits of the needle complex. The flagellar type-III secretion apparatus utilizes both the energy of the proton moti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004800
更新日期:2014-11-13 00:00:00
abstract::Ocular coloboma results from abnormal embryonic development and is often associated with additional ocular and systemic features. Coloboma is a highly heterogeneous disorder with many cases remaining unexplained. Whole exome sequencing from two cousins affected with dominant coloboma with microcornea, cataracts, and s...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005002
更新日期:2015-02-26 00:00:00
abstract::Seam cells in Caenorhabditis elegans provide a paradigm for the stem cell mode of division, with the ability to both self-renew and produce daughters that differentiate. The transcription factor RNT-1 and its DNA binding partner BRO-1 (homologues of the mammalian cancer-associated stem cell regulators RUNX and CBFβ, r...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002200
更新日期:2011-08-01 00:00:00
abstract::Hydrolysis of ATP by partition ATPases, although considered a key step in the segregation mechanism that assures stable inheritance of plasmids, is intrinsically very weak. The cognate centromere-binding protein (CBP), together with DNA, stimulates the ATPase to hydrolyse ATP and to undertake the relocation that incit...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003956
更新日期:2013-01-01 00:00:00
abstract::Successful reproduction is critical to pass genes to the next generation. Seminal proteins contribute to important reproductive processes that lead to fertilization in species ranging from insects to mammals. In Drosophila, the male's accessory gland is a source of seminal fluid proteins that affect the reproductive o...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030238
更新日期:2007-12-01 00:00:00
abstract::Elg1, the major subunit of a Replication Factor C-like complex, is critical to ensure genomic stability during DNA replication, and is implicated in controlling chromatin structure. We investigated the consequences of Elg1 loss for the dynamics of chromatin re-formation following DNA replication. Measurement of Okazak...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007783
更新日期:2018-11-12 00:00:00
abstract::Systems biology approaches that are based on the genetics of gene expression have been fruitful in identifying genetic regulatory loci related to complex traits. We use microarray and genetic marker data from an F2 mouse intercross to examine the large-scale organization of the gene co-expression network in liver, and...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020130
更新日期:2006-08-18 00:00:00
abstract::The model plant species Arabidopsis thaliana is successful at colonizing land that has recently undergone human-mediated disturbance. To investigate the prehistoric spread of A. thaliana, we applied approximate Bayesian computation and explicit spatial modeling to 76 European accessions sequenced at 876 nuclear loci. ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000075
更新日期:2008-05-16 00:00:00
abstract::Cis-regulation plays an essential role in the control of gene expression, and is particularly complex and poorly understood for developmental genes, which are subject to multiple levels of modulation. In this study, we performed a global analysis of the cis-acting elements involved in the control of the zebrafish deve...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007581
更新日期:2018-08-06 00:00:00