Abstract：
:We used clinical tissue from lethal metastatic castration-resistant prostate cancer (CRPC) patients obtained at rapid autopsy to evaluate diverse genomic, transcriptomic, and phosphoproteomic datasets for pathway analysis. Using Tied Diffusion through Interacting Events (TieDIE), we integrated differentially expressed master transcriptional regulators, functionally mutated genes, and differentially activated kinases in CRPC tissues to synthesize a robust signaling network consisting of druggable kinase pathways. Using MSigDB hallmark gene sets, six major signaling pathways with phosphorylation of several key residues were significantly enriched in CRPC tumors after incorporation of phosphoproteomic data. Individual autopsy profiles developed using these hallmarks revealed clinically relevant pathway information potentially suitable for patient stratification and targeted therapies in late stage prostate cancer. Here, we describe phosphorylation-based cancer hallmarks using integrated personalized signatures (pCHIPS) that shed light on the diversity of activated signaling pathways in metastatic CRPC while providing an integrative, pathway-based reference for drug prioritization in individual patients.
journal_name
Celljournal_title
Cellauthors
Drake JM,Paull EO,Graham NA,Lee JK,Smith BA,Titz B,Stoyanova T,Faltermeier CM,Uzunangelov V,Carlin DE,Fleming DT,Wong CK,Newton Y,Sudha S,Vashisht AA,Huang J,Wohlschlegel JA,Graeber TG,Witte ON,Stuart JMdoi
10.1016/j.cell.2016.07.007subject
Has Abstractpub_date
2016-08-11 00:00:00pages
1041-1054issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(16)30913-8journal_volume
166pub_type
杂志文章相关文献
CELL文献大全abstract：:Immunologically privileged sites express Fas ligand (FasL), which protects them from attack by activated T cells that express Fas and die upon contact with FasL. In an attempt to protect nonobese diabetic mice (NOD) from autoimmune diabetes, we made FasL transgenic NOD mice using the beta cell-specific rat insulin-1 p...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)80178-6
更新日期：1997-04-04 00:00:00
abstract：:A clone encoding PrP 27-30, the major protein in purified preparations of scrapie agent, was selected from a scrapie-infected hamster brain cDNA library by oligonucleotide probes corresponding to the N terminus of the protein. Southern blotting with PrP cDNA revealed a single gene with the same restriction patterns in...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(85)90333-2
更新日期：1985-04-01 00:00:00
abstract：:Although a great deal is known biochemically about peroxiredoxins (Prxs), little is known about their real physiological function. We show here that two cytosolic yeast Prxs, cPrxI and II, which display diversity in structure and apparent molecular weights (MW), can act alternatively as peroxidases and molecular chape...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2004.05.002
更新日期：2004-05-28 00:00:00
abstract：:Sleep is characterized by behavioral quiescence, homeostasis, increased arousal threshold, and rapid reversibility. Understanding how these properties are encoded by a neuronal circuit has been difficult, and no single molecular or neuronal pathway has been shown to be responsible for the regulation of sleep. Taking a...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2013.11.036
更新日期：2014-01-16 00:00:00
abstract：:Understanding human embryonic ventral midbrain is of major interest for Parkinson's disease. However, the cell types, their gene expression dynamics, and their relationship to commonly used rodent models remain to be defined. We performed single-cell RNA sequencing to examine ventral midbrain development in human and ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2016.09.027
更新日期：2016-10-06 00:00:00
abstract：:The use of optogenetic approaches has revealed new roles for intracellular protein condensates described in two papers in this issue of Cell (Bracha et. al., 2018; Shin et al., 2018). These results show that growing condensates are able to exert mechanical forces resulting in chromatin rearrangement, establishing a ne...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2018.11.020
更新日期：2018-11-29 00:00:00
abstract：:We describe a monoclonal antibody (anti-FC-1) that inhibits the attachment of chicken embryo fibroblasts to artificial substrates. In the immunofluorescence, anti-FC-1 also stained the focal contacts of the fibroblasts, organelles suggested to be involved in cell-substrate adhesion. This antibody was absorbed on the s...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(82)90322-1
更新日期：1982-12-01 00:00:00
abstract：:Mammals can taste a wide repertoire of chemosensory stimuli. Two unrelated families of receptors (T1Rs and T2Rs) mediate responses to sweet, amino acids, and bitter compounds. Here, we demonstrate that knockouts of TRPM5, a taste TRP ion channel, or PLCbeta2, a phospholipase C selectively expressed in taste tissue, ab...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/s0092-8674(03)00071-0
更新日期：2003-02-07 00:00:00
abstract：:We describe the isolation and characterization of two unusual amber suppressor forms of T4 tRNALeu. The sequences of the suppressor tRNAs can be described as hybrids of wild-type tRNALeu and suppressor tRNAGln molecules: the chain lengths and majority of the nucleotide residues corresponded to tRNALeu, but CUA anticod...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(84)90544-0
更新日期：1984-08-01 00:00:00
abstract：:In female mammals a "random choice" mechanism decides which of the two X chromosomes will be inactivated. It has been postulated that Xist is crucial for heterochromatinization and thus functions downstream of the choice mechanism. Here we report that females heterozygous for an internal deletion in the Xist gene, whi...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)81133-2
更新日期：1998-03-06 00:00:00
abstract：:NAD(+) is an important cofactor regulating metabolic homeostasis and a rate-limiting substrate for sirtuin deacylases. We show that NAD(+) levels are reduced in aged mice and Caenorhabditis elegans and that decreasing NAD(+) levels results in a further reduction in worm lifespan. Conversely, genetic or pharmacological...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2013.06.016
更新日期：2013-07-18 00:00:00
abstract：:Extraction of glycerinated chicken skeletal muscle with 0.6 M potassium iodide leaves a framework of insoluble components within each muscle fiber. This framework is composed primarily of planes of in-register Z discs that have been thickened by the accumulation of material on both sides of each disc during extraction...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(78)90051-x
更新日期：1978-12-01 00:00:00
abstract：:We have analyzed the transcriptional regulation of plastid genes during chloroplast development in illuminated spinach cotyledons and during leaf formation. The RNAs encoded by plastid genes accumulate with different kinetics during the developmental transitions. Using a novel plastid run-on transcription assay we dem...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(87)90290-x
更新日期：1987-05-08 00:00:00
abstract：:Although current immune-checkpoint therapy (ICT) mainly targets lymphoid cells, it is associated with a broader remodeling of the tumor micro-environment. Here, using complementary forms of high-dimensional profiling, we define differences across all hematopoietic cells from syngeneic mouse tumors during unrestrained ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2018.09.030
更新日期：2018-11-01 00:00:00
abstract：:Certain mutations can cause proteins to accumulate in neurons, leading to neurodegeneration. We recently showed, however, that upregulation of a wild-type protein, Ataxin1, caused by haploinsufficiency of its repressor, the RNA-binding protein Pumilio1 (PUM1), also causes neurodegeneration in mice. We therefore search...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2018.02.006
更新日期：2018-02-22 00:00:00
abstract：:The adenovirus E1a region encodes two closely related gene products: 243 and 289 amino acid phosphoproteins. These proteins differ in their primary sequence only by 46 amino acids unique to the 289 amino acid protein. By constructing single-base substitution mutants we localized two functional regions of these E1a pro...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(86)90704-x
更新日期：1986-09-26 00:00:00
abstract：:The intestinal epithelium is a highly structured tissue composed of repeating crypt-villus units. Enterocytes perform the diverse tasks of absorbing a wide range of nutrients while protecting the body from the harsh bacterium-rich environment. It is unknown whether these tasks are spatially zonated along the villus ax...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2018.08.063
更新日期：2018-11-01 00:00:00
abstract：:The global rise in the prevalence of obesity and associated co-morbidities such as type 2 diabetes, cardiovascular disease, and cancer represents a major public health concern. The biological response to increased consumption of palatable foods or a reduction in energy expenditure is highly variable between individual...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2015.03.008
更新日期：2015-03-26 00:00:00
abstract：:Nutrition presents unanswered scientific questions of high public health importance. We envision model systems composed of interacting gastrointestinal and metabolic tissues derived from human embryonic stem cells, populated by gut microbiota. The culture will be embedded in 3D scaffolds, creating a controlled experim...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2015.02.039
更新日期：2015-03-26 00:00:00
abstract：:Plant seedling development is capable of following 1 of 2 distinct morphogenic pathways: skotomorphogenesis in darkness and photomorphogenesis in light. Dark-grown Arabidopsis seedlings with recessive mutations at the constitutively photomorphogenic (COP1) locus indicate that the wild-type COP1 protein represses photo...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(92)90555-q
更新日期：1992-11-27 00:00:00
abstract：:Ras-related GTPases are positively regulated by guanine nucleotide exchange factors (GEFs) that promote the exchange of GDP for GTP. The crystal structure of the Sec7 domain GEF bound to nucleotide-free ARF1 GTPase has been determined at 2.8 A resolution and the structure of ARF1 in the GTP-analog form determined at 1...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)81754-7
更新日期：1998-10-16 00:00:00
abstract：:A second and minor DNA component containing 5s RNA genes has been purified from the genomic DNA of Xenopus laevis (XIt 5S DNA). Some of its physical and chemical characteristics are described. It contains a 5S RNA gene sequence which has some oocyte and some somatic-specific residues, as well as nucleotides which diff...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(77)90168-4
更新日期：1977-12-01 00:00:00
abstract：:Dimerization-driven activation of the intracellular kinase domains of the epidermal growth factor receptor (EGFR) upon extracellular ligand binding is crucial to cellular pathways regulating proliferation, migration, and differentiation. Inactive EGFR can exist as both monomers and dimers, suggesting that the mechanis...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2012.12.030
更新日期：2013-01-31 00:00:00
abstract：:In a 4-cell stage C. elegans embryo, signaling by the P2 blastomere induces anterior-posterior polarity in the adjacent EMS blastomere, leading to endoderm formation. We have taken genetic and reverse genetic approaches toward understanding the molecular basis for this induction. These studies have identified a set of...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)80531-0
更新日期：1997-08-22 00:00:00
abstract：:Clones containing five non-adult beta-globin genes were isolated from a library of BALB/c DNA. Together, the newly cloned regions comprise a contiguous block of 32 kb of the mouse genome. Restriction mapping of genomic DNA established the physical linkage of these non-adult genes to the two adult beta-globin genes as ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(80)90123-3
更新日期：1980-08-01 00:00:00
abstract：:Developmental analysis of a newly isolated maternal effect grandchildless mutant, tudor (tud), in Drosophila melanogaster indicates that tud+ activity is required during oogenesis for the determination and/or formation of primordial germ cells (pole cells) and for normal embryonic abdominal segmentation. Regardless of...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(85)90015-7
更新日期：1985-11-01 00:00:00
abstract：:The CD4 lymphocyte surface glycoprotein and the lck tyrosine protein kinase p56lck are found as a complex in T lymphocytes. We have defined the domains in both proteins that are responsible for this interaction by coexpressing hybrid and deleted forms of the two proteins in HeLa cells. We have found that the unique 32...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(89)90008-1
更新日期：1989-11-17 00:00:00
abstract：:Two dimensional gel electrophoresis (triton-acid-urea followed by SDS) has been used to resolve two previously uncharacterized, quantitatively minor histone variants in acid extracts from macronuclei of Tetrahymena thermophila. Utilizing techniques which allow characterization of these variants without purifying them ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(80)90307-4
更新日期：1980-07-01 00:00:00
abstract：:Basal cells are by definition located on the basolateral side of several epithelia, and they have never been observed reaching the lumen. Using high-resolution 3D confocal imaging, we report that basal cells extend long and slender cytoplasmic projections that not only reach toward the lumen but can cross the tight ju...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2008.10.020
更新日期：2008-12-12 00:00:00
abstract：:The chronic autoimmune diseases include multiple complex genetic disorders. Recently, genome-wide association studies (GWAS) have identified a large number of major loci, with many associations shared between various autoimmune diseases. These associations highlight key roles for lymphocyte activation and prioritize s...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2010.03.003
更新日期：2010-03-19 00:00:00
