Abstract:
:Amplification of 8p11-12 in human breast cancers is associated with increased proliferation and tumor grade and reduced metastasis-free patient survival. We identified Zeppo1 (zinc finger elbow-related proline domain protein 1) (FLJ14299/ZNF703) within this amplicon as a regulator of cell adhesion, migration, and proliferation in mammary epithelial cells. Overexpression of Zeppo1 reduces cell-cell adhesion and stimulates migration and proliferation. Knockdown of Zeppo1 induces adhesion and lumen formation. Zeppo1 regulates transcription, complexing with Groucho and repressing E-cadherin expression and Wnt and TGFβ reporter expression. Zeppo1 promotes expression of metastasis-associated p120-catenin isoform 1 and alters p120-catenin localization upon cell contact with the extracellular matrix. Significantly, Zeppo1 overexpression in a mouse breast cancer model increases lung metastases, while reducing Zeppo1 expression reduces both tumor size and the number of lung metastases. These results indicate that Zeppo1 is a key regulator of breast cancer progression.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Slorach EM,Chou J,Werb Zdoi
10.1101/gad.1998111subject
Has Abstractpub_date
2011-03-01 00:00:00pages
471-84issue
5eissn
0890-9369issn
1549-5477pii
gad.1998111journal_volume
25pub_type
杂志文章abstract::Organization into polarized three-dimensional structures defines whether epithelial cells are normal or malignant. In a model of morphogenesis, we show that inhibiting key signaling pathways in human breast cancer cells leads to "phenotypic reversion" of the malignant cells. Using architecture as an endpoint, we repor...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1990410
更新日期:2010-12-15 00:00:00
abstract::The mottler of white (mw) locus has been determined to interact with alleles of the white (w) eye color locus which are a subset of the transposable element insertion mutants. The transposable elements belong to six different types, including copia, and are located at several sites within the w gene. Three X-ray-induc...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.1.73
更新日期:1989-01-01 00:00:00
abstract::The epidemic of obesity and diabetes is causing an increased incidence of dyslipidemia-related heart failure. While the primary etiology of lipotoxic cardiomyopathy is an elevation of lipid levels resulting from an imbalance in energy availability and expenditure, increasing evidence suggests a relationship between dy...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1992411
更新日期:2011-01-15 00:00:00
abstract::A new gene, SCH9, was isolated from Saccharomyces cerevisiae by its ability to complement a cdc25ts mutation. Sequence analysis indicates that it encodes a 90,000-dalton protein with a carboxy-terminal domain homologous to yeast and mammalian cAMP-dependent protein kinase catalytic subunits. In addition to suppressing...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.5.517
更新日期:1988-05-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is thought to be an important, possibly essential, component of the process of tumor dissemination and metastasis. About 20%-30% of Hras mutant mouse skin carcinomas induced by chemical initiation/promotion protocols have undergone EMT. Reduced exposure to TPA-induced chronic in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.210427.112
更新日期:2013-03-15 00:00:00
abstract::The Hox gene products are transcription factors involved in specifying regional identity along the anteroposterior body axis. In the mouse, several single mutants for Hox genes show variably penetrant, partial homeotic transformations of vertebrae at their anterior limits of expression, suggesting that compound Hox mu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.13.1667
更新日期:1995-07-01 00:00:00
abstract::Cell cycle progression is dependent on two major waves of gene expression. Early cell cycle gene expression occurs during G1/S to generate factors required for DNA replication, while late cell cycle gene expression begins during G2 to prepare for mitosis. Here we demonstrate that the MuvB complex-comprised of LIN9, LI...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.181933.111
更新日期:2012-03-01 00:00:00
abstract::The organizer region, or dorsal blastopore lip, plays a central role in the initiation of gastrulation and the formation of the body axis during Xenopus development. A similar process can also be induced in ectodermal explants by activin or by injection of activin mRNA into embryos. We have searched early embryo-speci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.4.599
更新日期:1992-04-01 00:00:00
abstract::Specific recognition of splice sites within metazoan mRNA precursors (pre-mRNAs) is a potential stage for gene regulation by alternative splicing. Splicing factors of the SR protein family play a major role in this regulation, as they are required for early recognition of splice sites during spliceosome assembly. Here...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.6.740
更新日期:1999-03-15 00:00:00
abstract::We have developed a simple, effective genetic screen for mutant alleles of eukaryotic DNA topoisomerase I that manifest severely depressed or complete loss of enzymatic function. The screen is based on the extreme toxicity of vaccinia topoisomerase expression in the Escherichia coli lysogen strain BL21(DE3) and is not...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.515
更新日期:1990-04-01 00:00:00
abstract::An RNA-based gene silencing pathway that protects bacteria and archaea from viruses and other genome invaders is hypothesized to arise from guide RNAs encoded by CRISPR loci and proteins encoded by the cas genes. CRISPR loci contain multiple short invader-derived sequences separated by short repeats. The presence of v...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1742908
更新日期:2008-12-15 00:00:00
abstract::U6 small nuclear RNA is one of the spliceosomal RNAs involved in pre-mRNA splicing. In the fission yeast Schizosaccharomyces pombe, the U6 RNA gene was found to have an intron similar to a nuclear pre-mRNA intron, and it was proposed that the U6 intron might be inserted erroneously during pre-mRNA splicing. Using the ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.6.1022
更新日期:1991-06-01 00:00:00
abstract::The gamma delta T-cell receptor (TCR) is the first TCR to be expressed in ontogeny in all vertebrates in which it has been examined thoroughly. Murine gamma delta cell-surface protein is detected by the fourteenth day of gestation. In this work, the activation of gamma delta RNA has been studied. Data indicate that th...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.8.1304
更新日期:1990-08-01 00:00:00
abstract::Hepatitis B virus (HBV) infects humans and causes a wide range of clinical manifestations, from acute hepatitis to hepatocellular carcinoma (HCC). The HBV genome contains multiple promoters with gene expression regulated predominantly by the cellular transcription initiation machinery. Accordingly, the HBV-encoded pX,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.8.1217
更新日期:1998-04-15 00:00:00
abstract::The p53 inhibitor murine double-minute gene 2 (Mdm2) is a target for potential cancer therapies, however increased p53 function can be lethal. To directly address whether reduced Mdm2 function can inhibit tumorigenesis without causing detrimental side effects, we exploited a hypomorphic murine allele of mdm2 to compar...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1378506
更新日期:2006-01-01 00:00:00
abstract::The physiological functions of many vital tissues and organs continue to mature after birth, but the genetic mechanisms governing this postnatal maturation remain an unsolved mystery. Human pancreatic β cells produce and secrete insulin in response to physiological cues like glucose, and these hallmark functions impro...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.342378.120
更新日期:2021-01-14 00:00:00
abstract::The secreted Drosophila Hedgehog (Hh) protein induces transcription of specific genes by an unknown mechanism that requires the serpentine transmembrane protein Smoothened (Smo) and the transcription factor Cubitus interruptus (Ci). Protein kinase A (PKA) has been implicated in the mechanism of Hh signal transduction ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.17.2250
更新日期:1997-09-01 00:00:00
abstract::The heterochromatin-like structure formed by the yeast silent information regulator complex (SIR) represses transcription at the silent mating type loci and telomeres. Here, we report that tight protein-DNA complexes induce ectopic recruitment of the SIR complex, promoting gene silencing and changes in subnuclear loca...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.611011
更新日期:2011-07-01 00:00:00
abstract::The growth suppression function of the retinoblastoma protein (RB) is mediated by its interaction with a variety of cellular proteins. RB contains at least two protein-binding pockets: the large A/B pocket, which interacts with E2F and the D-type cyclins, and the C pocket, which interacts with the nuclear c-Abl tyrosi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.1.31
更新日期:1995-01-01 00:00:00
abstract::Ribosomal protein synthesis ceases upon maturation of Xenopus oocytes. We find that this cessation results from the dissociation of ribosomal protein mRNAs from polysomes and is accompanied by the deadenylation of these transcripts. A synthetic mRNA encoding ribosomal protein L1, microinjected into stage VI oocytes, i...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.5.598
更新日期:1988-05-01 00:00:00
abstract::To understand the organization of the transcriptional networks that govern cell differentiation, we have investigated the transcriptional circuitry controlling pseudohyphal development in Saccharomyces cerevisiae. The binding targets of Ste12, Tec1, Sok2, Phd1, Mga1, and Flo8 were globally mapped across the yeast geno...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1389306
更新日期:2006-02-15 00:00:00
abstract::Pre-mRNA processing is coupled with transcription. It is still unclear if the transcription machinery can also directly affect the cytoplasmic fate of a transcript, such as its intracellular localization. In yeast, the RNA-binding protein She2p binds several mRNAs and targets them for localization at the bud. Here we ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1937510
更新日期:2010-09-01 00:00:00
abstract::The Notch signaling pathway is essential for embryonic vascular development in vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand exhibit haploinsufficient lethality because of defects in vascular remodeling. We also describe vascular defects in embry...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1239204
更新日期:2004-10-15 00:00:00
abstract::Genomic imprinting is an epigenetic mechanism by which genes are expressed in a parental origin-dependent manner. We recently discovered that, like DNA methylation, oocyte-inherited H3K27me3 can also serve as an imprinting mark in mouse preimplantation embryos. In this study, we found H3K27me3 is strongly biased towar...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.323105.118
更新日期:2019-04-01 00:00:00
abstract::MicroRNAs (miRNAs) are approximately 22-nucleotide RNAs that are processed from characteristic precursor hairpins and pair to sites in messages of protein-coding genes to direct post-transcriptional repression. Here, we report that the miRNA iab-4 locus in the Drosophila Hox cluster is transcribed convergently from bo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1613108
更新日期:2008-01-01 00:00:00
abstract::The human RNA polymerase II (RNAPII)-associated factor complex (hPAFc) and its individual subunits have been implicated in human diseases, including cancer. However, its involvement in breast cancer awaits investigation. Using data mining and human breast cancer tissue microarrays, we found that Ctr9, the key scaffold...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.268722.115
更新日期:2015-10-15 00:00:00
abstract::Lethal yellow (Ay) is a mutation at the mouse agouti (a) locus that is associated with an all-yellow coat color, obesity, diabetes, tumors in heterozygotes, and preimplantation embryonic lethality in homozygotes. Previously, we cloned and characterized the wild-type agouti gene and demonstrated that it expresses a 0.8...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.7a.1203
更新日期:1993-07-01 00:00:00
abstract::A novel system to study early hematopoietic development is described. This report documents the in vitro capacity of murine embryonic stem (ES) cells to differentiate into hematopoietic precursors of most, if not all, of the colony-forming cells found in normal bone marrow. This system is used to correlate the genetic...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.5.728
更新日期:1991-05-01 00:00:00
abstract::Chromatin is organized into higher-order structures that form subcompartments in interphase nuclei. Different categories of specialized enzymes act on chromatin and regulate its compaction and biophysical characteristics in response to physiological conditions. We present an overview of the function of chromatin struc...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.307702.117
更新日期:2017-11-15 00:00:00
abstract::The RNA polymerase II core promoter is a structurally and functionally diverse transcriptional module. RNAi depletion and overexpression experiments revealed a genetic circuit that controls the balance of transcription from two core promoter motifs, the TATA box and the downstream core promoter element (DPE). In this ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1681808
更新日期:2008-09-01 00:00:00