Zeppo1 is a novel metastasis promoter that represses E-cadherin expression and regulates p120-catenin isoform expression and localization.


: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.


Genes Dev


Genes & development


Slorach EM,Chou J,Werb Z




Has Abstract


2011-03-01 00:00:00














  • Raf-induced MMP9 disrupts tissue architecture of human breast cells in three-dimensional culture and is necessary for tumor growth in vivo.

    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


    authors: Beliveau A,Mott JD,Lo A,Chen EI,Koller AA,Yaswen P,Muschler J,Bissell MJ

    更新日期:2010-12-15 00:00:00

  • Interaction of the mottler of white with transposable element alleles at the white locus in Drosophila melanogaster.

    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


    authors: Birchler JA,Hiebert JC,Rabinow L

    更新日期:1989-01-01 00:00:00

  • Phospholipid homeostasis regulates lipid metabolism and cardiac function through SREBP signaling in Drosophila.

    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


    authors: Lim HY,Wang W,Wessells RJ,Ocorr K,Bodmer R

    更新日期:2011-01-15 00:00:00

  • SCH9, a gene of Saccharomyces cerevisiae that encodes a protein distinct from, but functionally and structurally related to, cAMP-dependent protein kinase catalytic subunits.

    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


    authors: Toda T,Cameron S,Sass P,Wigler M

    更新日期:1988-05-01 00:00:00

  • Inflammation and Hras signaling control epithelial-mesenchymal transition during skin tumor progression.

    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


    authors: Wong CE,Yu JS,Quigley DA,To MD,Jen KY,Huang PY,Del Rosario R,Balmain A

    更新日期:2013-03-15 00:00:00

  • Compound mutants for the paralogous hoxa-4, hoxb-4, and hoxd-4 genes show more complete homeotic transformations and a dose-dependent increase in the number of vertebrae transformed.

    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


    authors: Horan GS,Ramírez-Solis R,Featherstone MS,Wolgemuth DJ,Bradley A,Behringer RR

    更新日期:1995-07-01 00:00:00

  • The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression.

    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


    authors: Sadasivam S,Duan S,DeCaprio JA

    更新日期:2012-03-01 00:00:00

  • A novel, activin-inducible, blastopore lip-specific gene of Xenopus laevis contains a fork head DNA-binding domain.

    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


    authors: Dirksen ML,Jamrich M

    更新日期:1992-04-01 00:00:00

  • Antagonism between RSF1 and SR proteins for both splice-site recognition in vitro and Drosophila development.

    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


    authors: Labourier E,Bourbon HM,Gallouzi IE,Fostier M,Allemand E,Tazi J

    更新日期:1999-03-15 00:00:00

  • Phenotypic selection and characterization of mutant alleles of a eukaryotic DNA topoisomerase I.

    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


    authors: Morham SG,Shuman S

    更新日期:1990-04-01 00:00:00

  • Cas6 is an endoribonuclease that generates guide RNAs for invader defense in prokaryotes.

    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


    authors: Carte J,Wang R,Li H,Terns RM,Terns MP

    更新日期:2008-12-15 00:00:00

  • mRNA-type introns in U6 small nuclear RNA genes: implications for the catalysis in pre-mRNA splicing.

    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


    authors: Tani T,Ohshima Y

    更新日期:1991-06-01 00:00:00

  • Developmentally regulated fetal thymic and extrathymic T-cell receptor gamma delta gene expression.

    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


    authors: Carding SR,Kyes S,Jenkinson EJ,Kingston R,Bottomly K,Owen JJ,Hayday AC

    更新日期:1990-08-01 00:00:00

  • pX, the HBV-encoded coactivator, suppresses the phenotypes of TBP and TAFII250 mutants.

    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


    authors: Haviv I,Matza Y,Shaul Y

    更新日期:1998-04-15 00:00:00

  • Tumor suppression and normal aging in mice with constitutively high p53 activity.

    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


    authors: Mendrysa SM,O'Leary KA,McElwee MK,Michalowski J,Eisenman RN,Powell DA,Perry ME

    更新日期:2006-01-01 00:00:00

  • SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells.

    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


    authors: Bevacqua RJ,Lam JY,Peiris H,Whitener RL,Kim S,Gu X,Friedlander MSH,Kim SK

    更新日期:2021-01-14 00:00:00

  • Dual pathways for induction of wingless expression by protein kinase A and Hedgehog in Drosophila embryos.

    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


    authors: Ohlmeyer JT,Kalderon D

    更新日期:1997-09-01 00:00:00

  • Tight protein-DNA interactions favor gene silencing.

    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


    authors: Dubarry M,Loïodice I,Chen CL,Thermes C,Taddei A

    更新日期:2011-07-01 00:00:00

  • Disruption of retinoblastoma protein function by coexpression of its C pocket fragment.

    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


    authors: Welch PJ,Wang JY

    更新日期:1995-01-01 00:00:00

  • Translational inactivation of ribosomal protein mRNAs during Xenopus oocyte maturation.

    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


    authors: Hyman LE,Wormington WM

    更新日期:1988-05-01 00:00:00

  • Target hub proteins serve as master regulators of development in yeast.

    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


    authors: Borneman AR,Leigh-Bell JA,Yu H,Bertone P,Gerstein M,Snyder M

    更新日期:2006-02-15 00:00:00

  • Cotranscriptional recruitment of She2p by RNA pol II elongation factor Spt4-Spt5/DSIF promotes mRNA localization to the yeast bud.

    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


    authors: Shen Z,St-Denis A,Chartrand P

    更新日期:2010-09-01 00:00:00

  • Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants.

    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


    authors: Krebs LT,Shutter JR,Tanigaki K,Honjo T,Stark KL,Gridley T

    更新日期:2004-10-15 00:00:00

  • Maternal-biased H3K27me3 correlates with paternal-specific gene expression in the human morula.

    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


    authors: Zhang W,Chen Z,Yin Q,Zhang D,Racowsky C,Zhang Y

    更新日期:2019-04-01 00:00:00

  • A single Hox locus in Drosophila produces functional microRNAs from opposite DNA strands.

    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


    authors: Stark A,Bushati N,Jan CH,Kheradpour P,Hodges E,Brennecke J,Bartel DP,Cohen SM,Kellis M

    更新日期:2008-01-01 00:00:00

  • Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis.

    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


    authors: Zeng H,Xu W

    更新日期:2015-10-15 00:00:00

  • The embryonic lethality of homozygous lethal yellow mice (Ay/Ay) is associated with the disruption of a novel RNA-binding protein.

    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


    authors: Michaud EJ,Bultman SJ,Stubbs LJ,Woychik RP

    更新日期:1993-07-01 00:00:00

  • Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression.

    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


    authors: Schmitt RM,Bruyns E,Snodgrass HR

    更新日期:1991-05-01 00:00:00

  • Chromatin and nucleosome dynamics in DNA damage and repair.

    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


    authors: Hauer MH,Gasser SM

    更新日期:2017-11-15 00:00:00

  • TBP, Mot1, and NC2 establish a regulatory circuit that controls DPE-dependent versus TATA-dependent transcription.

    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


    authors: Hsu JY,Juven-Gershon T,Marr MT 2nd,Wright KJ,Tjian R,Kadonaga JT

    更新日期:2008-09-01 00:00:00