The Hippo pathway oncoprotein YAP promotes melanoma cell invasion and spontaneous metastasis.

Abstract:

:Melanoma is a deadly form of skin cancer that accounts for a disproportionally large proportion of cancer-related deaths in younger people. Compared with most other skin cancers, a feature of melanoma is its high metastatic capacity, although the mechanisms that confer this are not well understood. The Hippo pathway is a key regulator of organ growth and cell fate that is deregulated in many cancers. To analyse the Hippo pathway in cutaneous melanoma, we generated a transcriptional signature of melanoma cells that overexpressed YAP, the key downstream Hippo pathway oncoprotein. YAP-mediated transcriptional activity varied in melanoma cell lines but did not cluster with known genetic drivers of melanomagenesis such as BRAF and NRAS mutations. Instead, it correlated strongly with published gene expression profiles linked to melanoma cell invasiveness and varied throughout the metastatic cascade in melanoma patient tumours. Consistent with this, YAP was both necessary and sufficient for melanoma cell invasion in vitro. In vivo, YAP promoted spontaneous melanoma metastasis, whilst the growth of YAP-expressing primary tumours was impeded. Finally, we identified the YAP target genes AXL, THBS1 and CYR61 as key mediators of YAP-induced melanoma cell invasion. These data suggest that YAP is a critical regulator of melanoma metastasis.

journal_name

Oncogene

journal_title

Oncogene

authors

Zhang X,Yang L,Szeto P,Abali GK,Zhang Y,Kulkarni A,Amarasinghe K,Li J,Vergara IA,Molania R,Papenfuss AT,McLean C,Shackleton M,Harvey KF

doi

10.1038/s41388-020-1362-9

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

5267-5281

issue

30

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-020-1362-9

journal_volume

39

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Interaction of HTLV-1 Tax and methyl-CpG-binding domain 2 positively regulates the gene expression from the hypermethylated LTR.

    abstract::Epigenetic regulation of gene expression is critical in the maintenance of cellular homeostasis. Dysregulation of normal epigenetic transcription occurs in abnormal physiological conditions, such as those seen in cancer cells and cells infected with parasites, making the mechanism underlying abnormal epigenetic transc...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208394

    authors: Ego T,Tanaka Y,Shimotohno K

    更新日期:2005-03-10 00:00:00

  • Oncogenic signaling by Kit tyrosine kinase occurs selectively on the Golgi apparatus in gastrointestinal stromal tumors.

    abstract::Gastrointestinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine kinase. Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. The characteristic intracellular accum...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.519

    authors: Obata Y,Horikawa K,Takahashi T,Akieda Y,Tsujimoto M,Fletcher JA,Esumi H,Nishida T,Abe R

    更新日期:2017-06-29 00:00:00

  • Serum induction of the fibroblast growth factor-binding protein (FGF-BP) is mediated through ERK and p38 MAP kinase activation and C/EBP-regulated transcription.

    abstract::The fibroblast growth factor-binding protein (FGF-BP) modulates FGF activity through binding and release from the extracellular matrix. Consequently, the expression of FGF-BP in certain tumor types is a rate-limiting regulator of FGF-mediated angiogenesis. FGF-BP is upregulated in squamous cell carcinoma by treatment ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204249

    authors: Harris VK,Kagan BL,Ray R,Coticchia CM,Liaudet-Coopman ED,Wellstein A,Tate Riegel A

    更新日期:2001-03-29 00:00:00

  • p53/BNIP3-dependent mitophagy limits glycolytic shift in radioresistant cancer.

    abstract::The role of p53 in genotoxic therapy-induced metabolic shift in cancers is not yet known. In this study, we investigated the role of p53 in the glycolytic shift in head and neck squamous cell carcinoma cell lines following irradiation. Isogenic p53-null radioresistant cancer cells established through cumulative irradi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0697-6

    authors: Chang HW,Kim MR,Lee HJ,Lee HM,Kim GC,Lee YS,Nam HY,Lee M,Jang HJ,Lee KE,Lee JC,Byun Y,Kim SW,Kim SY

    更新日期:2019-05-01 00:00:00

  • Association of a functional tandem repeats in the downstream of human telomerase gene and lung cancer.

    abstract::Chemoprevention has been widely explored as a promising strategy for controlling the incidence of lung cancer, the leading cause of cancer-related death. To maximize the benefit of lung cancer chemoprevention, it is important to identify individuals at high risk for the disease. The genetic background has been shown t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206852

    authors: Wang L,Soria JC,Chang YS,Lee HY,Wei Q,Mao L

    更新日期:2003-10-16 00:00:00

  • Carcinoma of the vulva: HPV and p53 mutations.

    abstract::Recent evidence suggests that squamous cell carcinoma of the vulva may have more than one etiology, with only some tumors associated with human papillomavirus (HPV). Cells infected with HPV produce a viral protein (E6) which binds to and causes rapid degradation of p53, possibly contributing to cellular transformation...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Lee YY,Wilczynski SP,Chumakov A,Chih D,Koeffler HP

    更新日期:1994-06-01 00:00:00

  • In vitro reconstruction of tumour initiation in a human epithelium.

    abstract::Knowledge of tumour initiation in human epithelia is limited by sample availability and difficulty in experimental manipulation of human cells. The thyroid is a useful model since, in addition to multiple tumour stages, it presents two distinct 'pathways' of tumorigenesis: 'follicular' tumours, in which ras oncogene m...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Bond JA,Wyllie FS,Rowson J,Radulescu A,Wynford-Thomas D

    更新日期:1994-01-01 00:00:00

  • A functional link between the tumour suppressors ARF and p33ING1.

    abstract::The ARF tumour suppressor protein plays a critical role in the activation of p53 in response to oncogenic stress. ARF can activate p53 through nucleolar sequestration of Mdm2. However, several lines of evidence indicate that this is not the only way of action of ARF, and alternative mechanisms must exist. p33ING1 is a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209526

    authors: González L,Freije JM,Cal S,López-Otín C,Serrano M,Palmero I

    更新日期:2006-08-24 00:00:00

  • The regulation of translation by the 5' untranslated region of Xenopus c-myc I mRNA during early development.

    abstract::The translational efficiency of chloramphenicol acetyltransferase (CAT) mRNA containing 5' untranslated region (UTR) sequences of Xenopus c-myc I mRNA was examined in the Xenopus oocyte and early embryo. In contrast to their reduced translation in the oocyte, CAT mRNAs containing 5' UTR sequences located between the c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Lazarus P

    更新日期:1992-05-01 00:00:00

  • The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression.

    abstract::The transcription factor NRF2 is the major mediator of oxidative stress responses and is closely connected to therapy resistance in tumors harboring activating mutations in the NRF2 pathway. In melanoma, such mutations are rare, and it is unclear to what extent melanomas rely on NRF2. Here we show that NRF2 suppresses...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-01477-8

    authors: Jessen C,Kreß JKC,Baluapuri A,Hufnagel A,Schmitz W,Kneitz S,Roth S,Marquardt A,Appenzeller S,Ade CP,Glutsch V,Wobser M,Friedmann-Angeli JP,Mosteo L,Goding CR,Schilling B,Geissinger E,Wolf E,Meierjohann S

    更新日期:2020-10-01 00:00:00

  • EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer.

    abstract::EDD (E3 isolated by differential display), located at chromosome 8q22.3, is the human orthologue of the Drosophila melanogaster tumour suppressor gene 'hyperplastic discs' and encodes a HECT domain E3 ubiquitin protein-ligase. To investigate the possible involvement of EDD in human cancer, several cancers from diverse...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206775

    authors: Clancy JL,Henderson MJ,Russell AJ,Anderson DW,Bova RJ,Campbell IG,Choong DY,Macdonald GA,Mann GJ,Nolan T,Brady G,Olopade OI,Woollatt E,Davies MJ,Segara D,Hacker NF,Henshall SM,Sutherland RL,Watts CK

    更新日期:2003-08-07 00:00:00

  • Olfactomedin 4 deletion induces colon adenocarcinoma in ApcMin/+ mice.

    abstract::Colon carcinogenesis is a multiple-step process involving the accumulation of a series of genetic and epigenetic alterations. The most commonly initiating event of intestinal carcinogenesis is mutation of the adenomatous polyposis coli (APC) gene, which leads to activation of the Wnt/β-catenin pathway. Olfactomedin 4 ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.58

    authors: Liu W,Li H,Hong SH,Piszczek GP,Chen W,Rodgers GP

    更新日期:2016-10-06 00:00:00

  • WW domain containing E3 ubiquitin protein ligase 1 targets the full-length ErbB4 for ubiquitin-mediated degradation in breast cancer.

    abstract::ErbB4, a member of the epidermal growth factor receptor family, plays a role in normal breast and breast cancer development by regulating mammary epithelial cell proliferation, survival and differentiation. In this study, we show that WWP1, a C2-WW-HECT type E3 ubiquitin ligase, binds, ubiquitinates and destructs ErbB...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.162

    authors: Li Y,Zhou Z,Alimandi M,Chen C

    更新日期:2009-08-20 00:00:00

  • Characterization of a third ras gene, rasB, that is expressed throughout the growth and development of Dictyostelium discoideum.

    abstract::Previous reports have indicated that the cellular slime mold Dictyostelium discoideum possesses two ras genes (rasG and rasD) and one rap gene (rap1). All three genes are developmentally regulated, with each showing a different pattern of transcription during the Dictyostelium life cycle. To establish whether there ar...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Daniel J,Spiegelman GB,Weeks G

    更新日期:1993-04-01 00:00:00

  • A model for gene evolution of the ets-1/ets-2 transcription factors based on structural and functional homologies.

    abstract::The chicken c-ets-1 locus encodes two transcription factors, p54c-ets-1 and p68c-ets-1 that differ in their N-termini, encoded respectively by the I54 and alpha beta exons. p68c-ets-1 equivalents are only found in birds and reptiles while p54c-ets-1 is widely conserved in vertebrates, from amphibians to mammals. Thus,...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Albagli O,Soudant N,Ferreira E,Dhordain P,Dewitte F,Begue A,Flourens A,Stehelin D,Leprince D

    更新日期:1994-11-01 00:00:00

  • Inhibition of endogenous reverse transcriptase antagonizes human tumor growth.

    abstract::Undifferentiated cells and embryos express high levels of endogenous non-telomerase reverse transcriptase (RT) of retroposon/retroviral origin. We previously found that RT inhibitors modulate cell growth and differentiation in several cell lines. We have now sought to establish whether high levels of RT activity are d...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208562

    authors: Sciamanna I,Landriscina M,Pittoggi C,Quirino M,Mearelli C,Beraldi R,Mattei E,Serafino A,Cassano A,Sinibaldi-Vallebona P,Garaci E,Barone C,Spadafora C

    更新日期:2005-06-02 00:00:00

  • The Ste20-like kinase SLK is required for ErbB2-driven breast cancer cell motility.

    abstract::The Ste20-like kinase, SLK, is involved in the control of cell motility through its effects on actin reorganization and focal adhesion turnover. Here we investigated the role of SLK in chemotaxis downstream of the tyrosine kinase receptor, HER2/ErbB2/Neu, which is frequently overexpressed in human breast cancers. Our ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.146

    authors: Roovers K,Wagner S,Storbeck CJ,O'Reilly P,Lo V,Northey JJ,Chmielecki J,Muller WJ,Siegel PM,Sabourin LA

    更新日期:2009-08-06 00:00:00

  • The p53 gene family.

    abstract::p73 and p63 are two recently discovered p53 homologs. Like p53, these proteins can recognize canonical p53 DNA-binding sites and, when overproduced, can activate p53-responsive target genes and induce apoptosis. Unlike p53, these genes undergo complex alternative splicing which, at least in the case of p63, yields pro...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1202955

    authors: Kaelin WG Jr

    更新日期:1999-12-13 00:00:00

  • Mutations in the catalytic subunit of class IA PI3K confer leukemogenic potential to hematopoietic cells.

    abstract::Constitutive activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway is observed in up to 70% of acute myelogenous leukemia. To investigate the relevance of an intrinsic PI3K-AKT pathway activation in hematopoietic malignancies, we analysed the effect of point mutations in the catalytic (p110alpha) and regulato...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.40

    authors: Horn S,Bergholz U,Jücker M,McCubrey JA,Trümper L,Stocking C,Bäsecke J

    更新日期:2008-07-03 00:00:00

  • Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines.

    abstract::We have compared the DNase I hypersensitivity of the regulatory region of two estrogen-regulated genes, pS2 and cathepsin D in hormone-dependent and -independent breast carcinoma cell lines. This strategy allowed the identification of two important control regions, one in pS2 and the other in cathepsin D genes. In the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202317

    authors: Giamarchi C,Solanas M,Chailleux C,Augereau P,Vignon F,Rochefort H,Richard-Foy H

    更新日期:1999-01-14 00:00:00

  • Prothymosin-alpha mRNA expression correlates with that of c-myc in human colon cancer.

    abstract::Prothymosin alpha (PT-alpha) is a nuclear protein involved in cell proliferation. Transcription of PT-alpha has been reported to be regulated by the c-myc gene in vitro. We identified PT-alpha as being overexpressed in a human colon cancer minus normal mucosa subtraction cDNA library. Northern blot (messenger RNA) ana...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Mori M,Barnard GF,Staniunas RJ,Jessup JM,Steele GD Jr,Chen LB

    更新日期:1993-10-01 00:00:00

  • HPV-16 E7 functions at the G1 to S phase transition in the cell cycle.

    abstract::Previous reports have demonstrated that E7 is the major transforming gene of HPV-16 and that continued expression of the gene is required to maintain the transformed phenotype of primary baby rat kidney cells transformed by HPV-16 E7 and EJ-ras. To investigate the point of action of E7 in the cell cycle we have utilis...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Banks L,Barnett SC,Crook T

    更新日期:1990-06-01 00:00:00

  • Integrated genomic profiling identifies two distinct molecular subtypes with divergent outcome in neuroblastoma with loss of chromosome 11q.

    abstract::Imbalances in chromosome 11q occur in approximately 30% of primary neuroblastoma and are associated with poor outcome. It has been suggested that 11q loss constitutes a distinct clinico-genetic neuroblastoma subgroup by affecting expression levels of corresponding genes. This study analysed the relationship of 11q los...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.390

    authors: Fischer M,Bauer T,Oberthür A,Hero B,Theissen J,Ehrich M,Spitz R,Eils R,Westermann F,Brors B,König R,Berthold F

    更新日期:2010-02-11 00:00:00

  • MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 on 19p13.

    abstract::Recently, the MLL gene at 11q23 was found to be involved in a subset of leukemias with an 11q23 abnormality. In the present study, we isolated chimeric cDNAs between the MLL and a gene designated MLLT3 at 9p22 from a cDNA library of an IMS-M1 cell line with a t(9;11)(p22;q23) translocation, a representative karyotypic...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Iida S,Seto M,Yamamoto K,Komatsu H,Tojo A,Asano S,Kamada N,Ariyoshi Y,Takahashi T,Ueda R

    更新日期:1993-11-01 00:00:00

  • Inactivation of the remaining allele of the WT1 gene in a Wilms' tumour from a WAGR patient.

    abstract::A candidate gene (WT1) has recently been described for the 11p13 tumour-suppressor gene involved in the development of Wilms' tumour. This gene encodes a zinc finger protein which can bind to a specific DNA sequence. We have found a 226 base deletion in the mRNA from a unilateral Wilms' tumour, which would cause a fra...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Brown KW,Watson JE,Poirier V,Mott MG,Berry PJ,Maitland NJ

    更新日期:1992-04-01 00:00:00

  • hHR23B is required for genotoxic-specific activation of p53 and apoptosis.

    abstract::Rad23 proteins function in both DNA repair and protein stability regulation. As ubiquitinated forms of p53 are stabilized after DNA damage in concert with p53 functional activation, and human Rad23 proteins (hHR23A and B) regulate p53 stability in unstressed cells, the role of hHR23B in post-genotoxin regulation of p5...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209865

    authors: Kaur M,Pop M,Shi D,Brignone C,Grossman SR

    更新日期:2007-02-22 00:00:00

  • Overexpression of CD44 in pl85(neu)-transfected NIH3T3 cells promotes an up-regulation of hyaluronic acid-mediated membrane-cytoskeleton interaction and cell adhesion.

    abstract::CD44 is a transmembrane glycoprotein known to bind hyaluronic acid (HA) in its extracellular domain and to contain at least one ankyrin-binding site in its cytoplasmic domain. In this study we have examined CD44 expression in a mouse fibroblast cell line transfected with the pl85(neu) oncogene cDNA. The results of RT-...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Zhu D,Bourguignon L

    更新日期:1996-06-06 00:00:00

  • Elevated expression of the junB proto-oncogene is essential for v-fos induced transformation of Rat-1 cells.

    abstract::We previously described the isolation of non-tumorigenic revertants from mutagenized populations of v-fos-transformed Rat-1 cells (Zarbl et al., 1987). In the present study we examined the possibility that the revertant phenotype resulted from mutations that altered the expression or activities of the c-jun or junB pr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Van Amsterdam JR,Wang Y,Sullivan RC,Zarbl H

    更新日期:1994-10-01 00:00:00

  • Regulation of cell migration, invasion and metastasis by IAP proteins and their antagonists.

    abstract::Inhibitor of apoptosis (IAP) proteins are a family comprised of a total of eight mammalian members that were initially described to act as endogenous inhibitors of caspases. In addition, extensive evidence has been accumulated over the last years showing that IAP proteins can regulate various signal transduction pathw...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2013.63

    authors: Fulda S

    更新日期:2014-02-06 00:00:00

  • From identification of the BTK kinase to effective management of leukemia.

    abstract::BTK is a cytoplasmic protein-tyrosine kinase, whose corresponding gene was isolated in the early 1990s. BTK was initially identified by positional cloning of the gene causing X-linked agammaglobulinemia and independently in a search for new kinases. Given the phenotype of affected patients, namely lack of B-lymphocyte...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2016.343

    authors: Smith CI

    更新日期:2017-04-01 00:00:00