A ubiquitin ligase, skeletrophin, is a negative regulator of melanoma invasion.


:Skeletrophin (mindbomb homolog 2 (MIB2)) is a RING (Really Interesting New Gene) finger-dependent ubiquitin ligase, which targets the intracellular region of Notch ligands. A previous immunohistochemical study demonstrated that skeletrophin was downregulated in many melanomas. In the present study, we have identified a promoter region of skeletrophin on a CpG island and detected aberrant methylation of this region in six of 31 invasive melanomas, but in none of 25 benign nevi or five non-invasive superficial spreading melanomas. Subsequently, we found that a zinc-finger transcriptional factor Snail, which is overexpressed in many melanoma cells, repressed the skeletrophin promoter activity via an E-box-related element and was involved in downregulation of skeletrophin. An activator protein-2, which has a tumor suppressor-like role in melanoma, increased skeletrophin expression. Interestingly, exogenously expressed skeletrophin reduced melanoma cell invasion in vitro and in vivo. Colony formation in soft agar was also reduced in a RING motif-dependent manner, without affecting cell growth. We also found that skeletrophin downregulated transcription of the Met oncogene, which encodes the hepatocyte growth factor receptor and plays a role in the determination of the invasive phenotype of many malignant tumors. Finally, exogenously expressed skeletrophin, but not its RING mutant, increased transcription of Hes1 gene, a downstream effector of Notch pathway in melanoma cells. The present findings indicate that skeletrophin might be a novel suppressor factor for melanoma invasion.






Takeuchi T,Adachi Y,Sonobe H,Furihata M,Ohtsuki Y




Has Abstract


2006-11-09 00:00:00
















  • Regional localization of the human c-rel locus using translocation chromosome analysis.

    abstract::The human cellular homolog of v-rel, the transforming gene of reticuloendotheliosis virus, strain T, was previously localized to 2 cent-2p13 by a combination of somatic cell hybrid and in situ hybridization analyses. In this study, we use translocation chromosome analysis to refine c-rel's genetic assignment to 2p12-2...


    pub_type: 杂志文章


    authors: Brownell E,Fell HP,Tucker PW,Geurts van Kessel AH,Hagemeijer A,Rice NR

    更新日期:1988-05-01 00:00:00

  • Identification and characterization of a BRAF fusion oncoprotein with retained autoinhibitory domains.

    abstract::Fusion proteins involving the BRAF serine/threonine kinase occur in many cancers. The oncogenic potential of BRAF fusions has been attributed to the loss of critical N-terminal domains that mediate BRAF autoinhibition. We used whole-exome and RNA sequencing in a patient with glioblastoma multiforme to identify a rearr...


    pub_type: 杂志文章


    authors: Weinberg F,Griffin R,Fröhlich M,Heining C,Braun S,Spohr C,Iconomou M,Hollek V,Röring M,Horak P,Kreutzfeldt S,Warsow G,Hutter B,Uhrig S,Neumann O,Reuss D,Heiland DH,von Kalle C,Weichert W,Stenzinger A,Brors B,Gli

    更新日期:2020-01-01 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,...


    pub_type: 杂志文章


    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

  • Overexpression of both catalytically active and -inactive cathepsin D by cancer cells enhances apoptosis-dependent chemo-sensitivity.

    abstract::The aspartic protease cathepsin D (cath-D) is a key mediator of induced-apoptosis and its proteolytic activity has been generally involved in this event. During apoptosis, cath-D is translocated to the cytosol. Because cath-D is one of the lysosomal enzymes that requires a more acidic pH to be proteolytically active r...


    pub_type: 杂志文章


    authors: Beaujouin M,Baghdiguian S,Glondu-Lassis M,Berchem G,Liaudet-Coopman E

    更新日期:2006-03-23 00:00:00

  • Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysin1 (MMP3) gene expression by physically interacting with the Fos/Jun complex.

    abstract::Collagenase1 (MMP1) and stromelysin1 (MMP3) are extracellular proteolytic enzymes that degrade connective tissue macromolecules and basement membranes. Both genes are regulated by the Ets and Fos/Jun families of transcription factors/oncoproteins. Here, we show that two members of the Ets-family, Ets2 and Erg and thei...


    pub_type: 杂志文章


    authors: Butticè G,Duterque-Coquillaud M,Basuyaux JP,Carrère S,Kurkinen M,Stéhelin D

    更新日期:1996-12-05 00:00:00

  • SUV39H1 regulates the progression of MLL-AF9-induced acute myeloid leukemia.

    abstract::Epigenetic regulations play crucial roles in leukemogenesis and leukemia progression. SUV39H1 is the dominant H3K9 methyltransferase in the hematopoietic system, and its expression declines with aging. However, the role of SUV39H1 via its-mediated repressive modification H3K9me3 in leukemogenesis/leukemia progression ...


    pub_type: 杂志文章


    authors: Chu Y,Chen Y,Guo H,Li M,Wang B,Shi D,Cheng X,Guan J,Wang X,Xue C,Cheng T,Shi J,Yuan W

    更新日期:2020-12-01 00:00:00

  • Talin1 phosphorylation activates β1 integrins: a novel mechanism to promote prostate cancer bone metastasis.

    abstract::Talins are adaptor proteins that regulate focal adhesion signaling by conjugating integrins to the cytoskeleton. Talins directly bind integrins and are essential for integrin activation. We previously showed that β1 integrins are activated in metastatic prostate cancer (PCa) cells, increasing PCa metastasis to lymph n...


    pub_type: 杂志文章


    authors: Jin JK,Tien PC,Cheng CJ,Song JH,Huang C,Lin SH,Gallick GE

    更新日期:2015-04-02 00:00:00

  • Reexpression of epigenetically silenced AML tumor suppressor genes by SUV39H1 inhibition.

    abstract::Reexpression of hypermethylated tumor suppressor genes using DNA methyltransferase (DNMT) and histone deacetylase inhibitors occurs by a mechanism whereby promoter demethylation is the dominant event. In support of this model, we found in acute myeloid leukemia cells with hypermethylated p15INK4B and E-cadherin promot...


    pub_type: 杂志文章


    authors: Lakshmikuttyamma A,Scott SA,DeCoteau JF,Geyer CR

    更新日期:2010-01-28 00:00:00

  • Identification of Elf-1 and B61 as high affinity ligands for the receptor tyrosine kinase MDK1.

    abstract::Mouse Developmental Kinase 1 (MDK1) is a receptor tyrosine kinase of the eck/eph subfamily expressed in a variety of tissues during early mouse embryogenesis. To obtain further insight into the function of MDK1, we determined identity and localisation of its physiological ligand(s). Staining whole embryos with fusion ...


    pub_type: 杂志文章


    authors: Ciossek T,Ullrich A

    更新日期:1997-01-09 00:00:00

  • Expression profiling identifies new function of collapsin response mediator protein 4 as a metastasis-suppressor in prostate cancer.

    abstract::Metastasis is the chief cause of mortality from cancer, but the mechanisms leading to metastasis are poorly understood. We used a proteomics approach to screen for metastasis-associated proteins and found that collapsin response mediator protein-4 (CRMP4) expression was inversely associated with the lymph node metasta...


    pub_type: 杂志文章


    authors: Gao X,Pang J,Li LY,Liu WP,Di JM,Sun QP,Fang YQ,Liu XP,Pu XY,He D,Li MT,Su ZL,Li BY

    更新日期:2010-08-12 00:00:00

  • An integrative analysis reveals functional targets of GATA6 transcriptional regulation in gastric cancer.

    abstract::Lineage-restricted transcription factors (TFs) are frequently mutated or overexpressed in cancer and contribute toward malignant behaviors; however, the molecular bases of their oncogenic properties are largely unknown. As TF activities are difficult to inhibit directly with small molecules, the genes and pathways the...


    pub_type: 杂志文章


    authors: Sulahian R,Casey F,Shen J,Qian ZR,Shin H,Ogino S,Weir BA,Vazquez F,Liu XS,Hahn WC,Bass AJ,Chan V,Shivdasani RA

    更新日期:2014-12-04 00:00:00

  • A novel p53 germline alteration identified in a late onset breast cancer kindred.

    abstract::Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central regio...


    pub_type: 杂志文章


    authors: Sun XF,Johannsson O,Håkansson S,Sellberg G,Nordenskjöld B,Olsson H,Borg A

    更新日期:1996-07-18 00:00:00

  • CpG island shore methylation regulates caveolin-1 expression in breast cancer.

    abstract::Caveolin-1 (Cav1) is an integral membrane, scaffolding protein found in plasma membrane invaginations (caveolae). Cav1 regulates multiple cancer-associated processes. In breast cancer, a tumor suppressive role for Cav1 has been suggested; however, Cav1 is frequently overexpressed in aggressive breast cancer subtypes, ...


    pub_type: 杂志文章


    authors: Rao X,Evans J,Chae H,Pilrose J,Kim S,Yan P,Huang RL,Lai HC,Lin H,Liu Y,Miller D,Rhee JK,Huang YW,Gu F,Gray JW,Huang TM,Nephew KP

    更新日期:2013-09-19 00:00:00

  • The transforming oncoproteins determine the mechanism by which p53 suppresses cell transformation: pRb-mediated growth arrest or apoptosis.

    abstract::To investigate the mechanisms by which p53 suppresses cell transformation, we used the simian virus 40 (SV40) large T antigen (LTag), the adenovirus E1a proteins, and an activated ras protein (EJ-ras), to examine different pathways of transformation for their susceptibility to suppression by p53: While p53 can suppres...


    pub_type: 杂志文章


    authors: Hansen R,Reddel R,Braithwaite A

    更新日期:1995-12-21 00:00:00

  • The 'WS motif' common to v-mpl and members of the cytokine receptor superfamily is dispensable for myeloproliferative leukemia virus pathogenicity.

    abstract::Several motifs are conserved in the extracellular domain of the cloned chains of the recently described cytokine receptor superfamily. One of them, usually close to the transmembrane region, is the 'WS motif'. Its function remains unknown, but it has been recently shown that the integrity of this motif is essential fo...


    pub_type: 杂志文章


    authors: Bénit L,Charon M,Cocault L,Wendling F,Gisselbrecht S

    更新日期:1993-03-01 00:00:00

  • The retinoblastoma protein modulates expression of genes coding for diverse classes of proteins including components of the extracellular matrix.

    abstract::The product of the retinoblastoma susceptibility gene, pRb, is a negative regulator of cell growth. It functions by regulating the activity of transcription factors. Rb represses some genes by sequestering or inactivating the positive transcription factor E2F and seems to activate some others by interacting with facto...


    pub_type: 杂志文章


    authors: Rohde M,Warthoe P,Gjetting T,Lukas J,Bartek J,Strauss M

    更新日期:1996-06-06 00:00:00

  • Recurrent allelic deletions at mouse chromosomes 4 and 14 in Myc-induced liver tumors.

    abstract::Transgenic mice expressing the c-Myc oncogene driven by woodchuck hepatitis virus (WHV) regulatory sequences develop hepatocellular carcinoma with a high frequency. To investigate genetic lesions that cooperate with Myc in liver carcinogenesis, we conducted a genome-wide scan for loss of heterozygosity (LOH) and mutat...


    pub_type: 杂志文章


    authors: Wu Y,Renard CA,Apiou F,Huerre M,Tiollais P,Dutrillaux B,Buendia MA

    更新日期:2002-02-28 00:00:00

  • Human cancer cells require ATR for cell cycle progression following exposure to ionizing radiation.

    abstract::The vast majority of cancer cells have defective checkpoints that permit the cell cycle to progress in the presence of double-strand DNA breaks (DSBs) caused by ionizing radiation (IR) and radiomimetic drugs. ATR (ataxia telangiectasia-mutated and Rad3-related) has recently been shown to be activated by DSBs, although...


    pub_type: 杂志文章


    authors: Hurley PJ,Wilsker D,Bunz F

    更新日期:2007-04-19 00:00:00

  • p53- and p21-dependent premature APC/C-Cdh1 activation in G2 is part of the long-term response to genotoxic stress.

    abstract::The long-term cellular response to DNA damage is controlled by the tumor suppressor p53. It results in cell-cycle arrest followed by DNA repair and, depending on the degree of damage inflicted, premature senescence or apoptotic cell death. Here we show that in normal diploid fibroblasts the ubiquitin ligase anaphase-p...


    pub_type: 杂志文章


    authors: Wiebusch L,Hagemeier C

    更新日期:2010-06-17 00:00:00

  • The neural guidance receptor Plexin C1 delays melanoma progression.

    abstract::Plexin C1 is a type I transmembrane receptor with intrinsic R-Ras GTPase activity, which regulates cytoskeletal remodeling and adhesion in normal human melanocytes. Melanocytes are pigment-producing cells of the epidermis, precursors for melanoma, and express high levels of Plexin C1, which is lost in melanoma in vitr...


    pub_type: 杂志文章


    authors: Chen Y,Soong J,Mohanty S,Xu L,Scott G

    更新日期:2013-10-10 00:00:00

  • Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas.

    abstract::The NF2 gene product, merlin/schwannomin, is a cytoskeleton organizer with unique growth-inhibiting activity in specific cell types. A narrow spectrum of tumors is associated with NF2 deficiency, mainly schwannomas and meningiomas, suggesting cell-specific mechanisms of growth control. We have investigated merlin func...


    pub_type: 杂志文章


    authors: Lallemand D,Manent J,Couvelard A,Watilliaux A,Siena M,Chareyre F,Lampin A,Niwa-Kawakita M,Kalamarides M,Giovannini M

    更新日期:2009-02-12 00:00:00

  • Essential roles of ERK-mediated phosphorylation of vinexin in cell spreading, migration and anchorage-independent growth.

    abstract::Vinexin is an adaptor protein supposed to play pivotal roles in various cellular events such as cell adhesion, cytoskeletal organization, signaling and gene expression. Despite the possible importance, physiological functions and regulatory mechanisms of vinexin are largely unknown. In addition, although vinexin was r...


    pub_type: 杂志文章


    authors: Mizutani K,Ito H,Iwamoto I,Morishita R,Deguchi T,Nozawa Y,Asano T,Nagata KI

    更新日期:2007-11-01 00:00:00

  • Overlapping gene expression profiles of cell migration and tumor invasion in human bladder cancer identify metallothionein 1E and nicotinamide N-methyltransferase as novel regulators of cell migration.

    abstract::Cell migration is essential to cancer invasion and metastasis and is spatially and temporally integrated through transcriptionally dependent and independent mechanisms. As cell migration is studied in vitro, it is important to identify genes that both drive cell migration and are biologically relevant in promoting inv...


    pub_type: 杂志文章


    authors: Wu Y,Siadaty MS,Berens ME,Hampton GM,Theodorescu D

    更新日期:2008-11-06 00:00:00

  • Integrative molecular and functional profiling of ERBB2-amplified breast cancers identifies new genetic dependencies.

    abstract::Overexpression of the receptor tyrosine kinase ERBB2 (also known as HER2) occurs in around 15% of breast cancers and is driven by amplification of the ERBB2 gene. ERBB2 amplification is a marker of poor prognosis, and although anti-ERBB2-targeted therapies have shown significant clinical benefit, de novo and acquired ...


    pub_type: 杂志文章


    authors: Shiu KK,Wetterskog D,Mackay A,Natrajan R,Lambros M,Sims D,Bajrami I,Brough R,Frankum J,Sharpe R,Marchio C,Horlings H,Reyal F,van der Vijver M,Turner N,Reis-Filho JS,Lord CJ,Ashworth A

    更新日期:2014-01-30 00:00:00

  • Phorbol esters inhibit fibroblast growth factor-2-stimulated fibroblast proliferation by a p38 MAP kinase dependent pathway.

    abstract::Treatment of fibroblasts with the phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA), specifically inhibits fibroblast growth factor-2 (FGF-2) induced proliferation. TPA treatment has little or no effect on FGF receptor activation but specifically inhibits the activation of p38 MAPK but not other downstream si...


    pub_type: 杂志文章


    authors: Maher P

    更新日期:2002-03-27 00:00:00

  • Cell size regulation by the human TSC tumor suppressor proteins depends on PI3K and FKBP38.

    abstract::TSC1 and TSC2 are responsible for the tumor suppressor gene syndrome tuberous sclerosis (TSC). Mammalian TSC genes have been shown to be involved in cell cycle regulation. Recently, in Drosophila, these data have been confirmed and TSC genes have further been demonstrated to affect cell size control. Here we provide s...


    pub_type: 杂志文章


    authors: Rosner M,Hofer K,Kubista M,Hengstschläger M

    更新日期:2003-07-31 00:00:00

  • The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression.

    abstract::In this study, we examined the role of the E-cadherin-repressed gene human Nanos1 (hNanos1) in tumor invasion process. First, our in vivo study revealed that hNanos1 mRNAs were overexpressed in invasive lung carcinomas. Moreover, hNanos1 was co-localized with MT1-MMP (membrane type 1-matrix metalloproteinase) in E-cad...


    pub_type: 杂志文章


    authors: Bonnomet A,Polette M,Strumane K,Gilles C,Dalstein V,Kileztky C,Berx G,van Roy F,Birembaut P,Nawrocki-Raby B

    更新日期:2008-06-12 00:00:00

  • Phosphorylation-dependent cleavage regulates von Hippel Lindau proteostasis and function.

    abstract::Loss of von Hippel Lindau (VHL) protein function is a key driver of VHL diseases, including sporadic and inherited clear cell renal cell carcinoma. Modulation of the proteostasis of VHL, especially missense point-mutated VHL, is a promising approach to augmenting VHL levels and function. VHL proteostasis is regulated ...


    pub_type: 杂志文章


    authors: German P,Bai S,Liu XD,Sun M,Zhou L,Kalra S,Zhang X,Minelli R,Scott KL,Mills GB,Jonasch E,Ding Z

    更新日期:2016-09-22 00:00:00

  • FBXO10 deficiency and BTK activation upregulate BCL2 expression in mantle cell lymphoma.

    abstract::Targeting Bruton tyrosine kinase (BTK) by ibrutinib is an effective treatment for patients with relapsed/refractory mantle cell lymphoma (MCL). However, both primary and acquired resistance to ibrutinib have developed in a significant number of these patients. A combinatory strategy targeting multiple oncogenic pathwa...


    pub_type: 杂志文章


    authors: Li Y,Bouchlaka MN,Wolff J,Grindle KM,Lu L,Qian S,Zhong X,Pflum N,Jobin P,Kahl BS,Eickhoff JC,Wuerzberger-Davis SM,Miyamoto S,Thomas CJ,Yang DT,Capitini CM,Rui L

    更新日期:2016-12-01 00:00:00

  • A delayed chemically induced tumorigenesis in Brca2 mutant mice.

    abstract::BRCA2 is a breast cancer susceptibility gene. Germline mutations of BRCA2 account for about 10-30% of familial breast cancer cases. Consistent with its tumor-suppressor activity, BRCA2 plays an important role in DNA repair. To assess the susceptibility of carriers of mutant BRCA2 to tumorigenesis induced by DNA-damagi...


    pub_type: 杂志文章


    authors: Yan DH,Wen Y,Su LK,Xia W,Wang SC,Zhang S,Gan L,Lee DF,Spohn B,Frey JA,Hortobagyi GN,Hung MC

    更新日期:2004-03-11 00:00:00