Src stimulates fibroblast growth factor receptor-2 shedding by an ADAM15 splice variant linked to breast cancer.

Abstract:

:ADAMs (a disintegrin and metalloproteinase) have important roles in development and diseases such as cancer. Previously, an ADAM15 splice variant (ADAM15B), which contains an inserted cytoplasmic Src-binding site, was linked to clinical aggressiveness in breast cancer, yet little was known about how this splice variant affects the function of ADAM15. Here, we show that ADAM15B has enhanced catalytic activity in cell-based assays compared with ADAM15A, which lacks a Src-binding site, using shedding of fibroblast growth factor receptor 2iiib variant as an assay for catalytic activity. Moreover, the enhanced activity of ADAM15B compared with ADAM15A depends on Src because it is abolished by Src-kinase inhibitors and in Src(-/-) cells, but not in Src(-/-) cells rescued with Src. These findings provide insights into the mechanism of how a splice variant linked to clinical agressiveness in breast cancer causes increased activity of ADAM15B, and suggest that inhibitors of the ADAM15 protease activity or of the interaction of ADAM15B with Src could be useful to treat breast cancer in patients with dysregulated ADAM15B.

journal_name

Cancer Res

journal_title

Cancer research

authors

Maretzky T,Le Gall SM,Worpenberg-Pietruk S,Eder J,Overall CM,Huang XY,Poghosyan Z,Edwards DR,Blobel CP

doi

10.1158/0008-5472.CAN-08-4766

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

4573-6

issue

11

eissn

0008-5472

issn

1538-7445

pii

69/11/4573

journal_volume

69

pub_type

杂志文章
  • A novel, macrophage migration inhibitory factor suicide substrate inhibits motility and growth of lung cancer cells.

    abstract::Although chemokine and growth factor receptors are attractive and popular targets for cancer therapeutic intervention, structure-based targeting of the ligands themselves is generally not considered practical. New evidence indicates that a notable exception to this is macrophage migration inhibitory factor (MIF). MIF,...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-6227

    authors: Winner M,Meier J,Zierow S,Rendon BE,Crichlow GV,Riggs R,Bucala R,Leng L,Smith N,Lolis E,Trent JO,Mitchell RA

    更新日期:2008-09-15 00:00:00

  • HuR, a RNA stability factor, is expressed in malignant brain tumors and binds to adenine- and uridine-rich elements within the 3' untranslated regions of cytokine and angiogenic factor mRNAs.

    abstract::Tumors of the central nervous system (CNS) often have sustained expression of labile genes, including angiogenic growth factors and immunosuppressive cytokines, which promote tumor progression. Stabilization of the RNA transcripts for these genes, such as vascular endothelial growth factor (VEGF), is an important mole...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Nabors LB,Gillespie GY,Harkins L,King PH

    更新日期:2001-03-01 00:00:00

  • The suppression of drug-induced apoptosis by activation of v-ABL protein tyrosine kinase.

    abstract::Cells with a temperature-sensitive mutant of the v-abl oncoprotein (IC.DP) were treated with the anticancer drugs melphalan or hydroxyurea. At the restrictive temperature for v-ABL protein tyrosine kinase activity, drug-treated IC.DP cells died by apoptosis. In contrast, apoptotic cell death induced by either drug was...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Chapman RS,Whetton AD,Dive C

    更新日期:1994-10-01 00:00:00

  • High-mobility group A1 proteins inhibit expression of nucleotide excision repair factor xeroderma pigmentosum group A.

    abstract::Cells that overexpress high-mobility group A1 (HMGA1) proteins exhibit deficient nucleotide excision repair (NER) after exposure to DNA-damaging agents, a condition ameliorated by artificially lowering intracellular levels of these nonhistone proteins. One possible mechanism for this NER inhibition is down-regulation ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-1689

    authors: Adair JE,Maloney SC,Dement GA,Wertzler KJ,Smerdon MJ,Reeves R

    更新日期:2007-07-01 00:00:00

  • Overexpression of the tumor suppressor gene phosphatase and tensin homologue partially inhibits wnt-1-induced mammary tumorigenesis.

    abstract::The tumor suppressor phosphatase and tensin homologue (PTEN) is involved in cell proliferation, adhesion, and apoptosis. PTEN overexpression in mammary epithelium leads to reduced cell number and impaired differentiation and secretion. In contrast, overexpression of the proto-oncogene Wnt-1 in mammary epithelium leads...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-0181

    authors: Zhao H,Cui Y,Dupont J,Sun H,Hennighausen L,Yakar S

    更新日期:2005-08-01 00:00:00

  • Trends in program project grant funding at the National Cancer Institute.

    abstract::In summary, analysis of the P01 program indicates that differences exist in scores and funding requirements between purely basic and translational P01s; P01 funding has been stable and the P01 policies consistent; growth in average costs for P01s has lagged compared to R01s; P01 grantees have a higher success rate tha...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Broder S,Cushing M

    更新日期:1993-02-01 00:00:00

  • Differential effects of dietary linoleic acid on mouse skin-tumor promotion and mammary carcinogenesis.

    abstract::On the basis of reports of rat mammary- and pancreas-tumor models, we hypothesized that an increase in consumption of linoleic acid (LA) would also cause an enhancement in mouse skin-tumor promotion. SEN-CAR mice were placed on diets containing 0.8%, 2.2%, 3.5%, 4.5%, 5.6%, 7.0%, or 8.4% LA, 1 week after initiation wi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Fischer SM,Leyton J,Lee ML,Locniskar M,Belury MA,Maldve RE,Slaga TJ,Bechtel DH

    更新日期:1992-04-01 00:00:00

  • Protein kinase C delta involvement in mammary tumor cell metastasis.

    abstract::Metastasis requires cytoskeletal remodeling for migration, adhesion, and extravasation of metastatic cells. Although protein kinase C (PKC) is involved in tumor promotion/progression and cytoskeletal remodeling, its role in metastasis has not been defined. PKCdelta levels are increased in highly metastatic 13762NF mam...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kiley SC,Clark KJ,Goodnough M,Welch DR,Jaken S

    更新日期:1999-07-01 00:00:00

  • Antagonistic effect of glucocorticoids on retinoic acid induced growth inhibition and morphological alterations of a human cell line.

    abstract::When the human cell line NHIK 3025 was exposed to retinoic acid (1 nM; 10 microM), the cell cycle time was prolonged. Experiments using cells synchronized by mitotic selection showed that the retinoic acid induced growth delay was barely seen within the first cell cycle after exposure to 10 microM retinoic acid, where...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bakke O

    更新日期:1986-03-01 00:00:00

  • Cancer cachexia syndrome developed in nude mice bearing melanoma cells producing leukemia-inhibitory factor.

    abstract::Melanoma-derived lipoprotein lipase inhibitor (MLPLI) is a factor purified from the conditioned medium of a human melanoma cell line, SEKI, which induced severe cachexia in tumor-bearing nude mice. Amino acid sequencing revealed that the amino-terminal portion was identical to that of leukemia-inhibitory factor (LIF)....

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Mori M,Yamaguchi K,Honda S,Nagasaki K,Ueda M,Abe O,Abe K

    更新日期:1991-12-15 00:00:00

  • Increases in brain tumor and cerebral blood flow by blood-perfluorochemical emulsion (Fluosol-DA) exchange.

    abstract::It has been suggested that oxygen-carrying blood substitutes, perfluorochemical (PFC) emulsions, can increase blood flow and oxygen delivery to poorly perfused tumor regions. Local cerebral blood flow was measured in male Wistar rats bearing intracranial Walker 256 tumor with and without blood-PFC exchange using [14C]...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hiraga S,Klubes P,Owens ES,Cysyk RL,Blasberg RG

    更新日期:1987-06-15 00:00:00

  • Nestin Mediates Hedgehog Pathway Tumorigenesis.

    abstract::The intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem-like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here, we report that Nestin binds the hedgehog pathway transcription factor Gli3 to ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-16-1547

    authors: Li P,Lee EH,Du F,Gordon RE,Yuelling LW,Liu Y,Ng JM,Zhang H,Wu J,Korshunov A,Pfister SM,Curran T,Yang ZJ

    更新日期:2016-09-15 00:00:00

  • Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation.

    abstract::The Notch family of proteins plays an integral role in determining cell fates, such as proliferation, differentiation, and apoptosis. We show that Notch-1 and its ligands, Delta-like-1 and Jagged-1, are overexpressed in many glioma cell lines and primary human gliomas. Immunohistochemistry of a primary human glioma ti...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-1890

    authors: Purow BW,Haque RM,Noel MW,Su Q,Burdick MJ,Lee J,Sundaresan T,Pastorino S,Park JK,Mikolaenko I,Maric D,Eberhart CG,Fine HA

    更新日期:2005-03-15 00:00:00

  • Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome.

    abstract::Glial tumors progress to malignant grades by heightened proliferation and relentless dispersion throughout the central nervous system. Understanding genetic and biochemical processes that foster these behaviors is likely to reveal specific and effective targets for therapeutic intervention. Our current report shows th...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-0418

    authors: Tran NL,McDonough WS,Savitch BA,Fortin SP,Winkles JA,Symons M,Nakada M,Cunliffe HE,Hostetter G,Hoelzinger DB,Rennert JL,Michaelson JS,Burkly LC,Lipinski CA,Loftus JC,Mariani L,Berens ME

    更新日期:2006-10-01 00:00:00

  • Combined modality therapy with bleomycin, hyperthermia, and radiation.

    abstract::In an attempt to develop better combination therapies for use with local radiation, the interaction between bleomycin and hyperthermia +/- radiation was studied in the FSaIIC tumor system. In cells exposed in vitro to bleomycin at 37 degrees C and at pH 7.40, the drug was substantially more toxic toward normally oxyge...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Teicher BA,Herman TS,Holden SA

    更新日期:1988-11-15 00:00:00

  • Expression of DMBT1, a candidate tumor suppressor gene, is frequently lost in lung cancer.

    abstract::DMBT1 is a candidate tumor suppressor gene located at 10q25.3-26.1. Homozygous deletion of the gene was found in a subset of medulloblastoma and glioblastoma multiforme; lack of expression was noted in the majority of these tumors. In adult tissues, DMBT1 is highly expressed only in lung and small intestine tissues, i...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Wu W,Kemp BL,Proctor ML,Gazdar AF,Minna JD,Hong WK,Mao L

    更新日期:1999-04-15 00:00:00

  • Do MDM2 SNP309 and TP53 R72P interact in breast cancer susceptibility? A large pooled series from the breast cancer association consortium.

    abstract::Association studies in large series of breast cancer patients can be used to identify single-nucleotide polymorphisms (SNP) contributing to breast cancer susceptibility. Previous studies have suggested associations between variants in TP53 (R72P) and MDM2 (SNP309) and cancer risk. Data from molecular studies suggest a...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-0738

    authors: Schmidt MK,Reincke S,Broeks A,Braaf LM,Hogervorst FB,Tollenaar RA,Johnson N,Fletcher O,Peto J,Tommiska J,Blomqvist C,Nevanlinna HA,Healey CS,Dunning AM,Pharoah PD,Easton DF,Dörk T,Van't Veer LJ,Breast Cancer Associati

    更新日期:2007-10-01 00:00:00

  • Characterization of estrogen and progesterone receptors and the dissociated regulation of growth and progesterone receptor stimulation by estrogen in MDA-MB-134 human breast cancer cells.

    abstract::We have examined the properties of the estrogen receptor and progesterone receptor in MDA-MB-134 human breast cells and have evaluated the effects of estrogen on cell proliferation and progesterone receptor levels in these cells as indices of hormonal sensitivity. These cells contain high levels of estrogen receptor (...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Reiner GC,Katzenellenbogen BS

    更新日期:1986-03-01 00:00:00

  • Anticachectic effects of formoterol: a drug for potential treatment of muscle wasting.

    abstract::In cancer cachexia both cardiac and skeletal muscle suffer an important protein mobilization as a result of increased proteolysis. Administration of the beta2-agonist formoterol to both rats and mice bearing highly cachectic tumors resulted in an important reversal of the muscle-wasting process. The anti-wasting effec...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-0425

    authors: Busquets S,Figueras MT,Fuster G,Almendro V,Moore-Carrasco R,Ametller E,Argilés JM,López-Soriano FJ

    更新日期:2004-09-15 00:00:00

  • C-SRC tyrosine kinase activity is associated with tumor colonization in bone and lung in an animal model of human breast cancer metastasis.

    abstract::The proto-oncogene, c-src, has been implicated in the tumorigenesis in breast cancer. However, the relationship of c-src with distant metastasis is unclear. Moreover, the role of c-src in organ-preferential metastasis of breast cancer is unknown. Because breast cancer has a strong predilection for metastasizing to bon...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Myoui A,Nishimura R,Williams PJ,Hiraga T,Tamura D,Michigami T,Mundy GR,Yoneda T

    更新日期:2003-08-15 00:00:00

  • Comparative studies of DNA cross-linking and cytotoxicity in Burkitt's lymphoma cell lines treated with cis-diamminedichloroplatinum(II) and L-phenylalanine mustard.

    abstract::Three Burkitt's lymphoma cell lines were studied for their response to cis-diamminedichloroplatinum(II) (cis-DDP) and L-phenylalanine mustard (L-PAM) with the objective of relating cytotoxicity to DNA cross-linking in human cells. Cytotoxicity was measured by cell proliferation and colony formation assays. DNA interst...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ducore JM,Erickson LC,Zwelling LA,Laurent G,Kohn KW

    更新日期:1982-03-01 00:00:00

  • Factors influencing the anticarcinogenic efficacy of selenium in dimethylbenz[a]anthracene-induced mammary tumorigenesis in rats.

    abstract::The present study was designed to investigate the effect of selenium supplementation on dimethylbenz[a]anthracene-induced mammary tumorigenesis in female Sprague-Dawley rats fed either a 5 or 25% corn oil diet, denoted as low fat (LF) or high fat (HF), respectively. Selenium supplementation of LF and HF diets were beg...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ip C

    更新日期:1981-07-01 00:00:00

  • Characterization of a human teratocarcinoma cell assay for inhibitors of metabolic cooperation.

    abstract::Although a Chinese hamster V79 cell-based assay for inhibitors of metabolic cooperation is currently available, the development of a human cell-based assay is desirable in order to avoid inappropriate extrapolation from animal cells to human cells. Cells derived from a human teratocarcinoma cell line (designated PA-1)...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kavanagh TJ,Chang CC,Trosko JE

    更新日期:1986-03-01 00:00:00

  • A noninvasive procedure for early-stage discrimination of malignant and precancerous vocal fold lesions based on laryngeal dynamics analysis.

    abstract::About two thirds of laryngeal cancers originate at the vocal cords. Early-stage detection of malignant vocal fold alterations, including a discrimination of premalignant lesions, represents a major challenge in laryngology as precancerous vocal fold lesions and small carcinomas are difficult to distinguish by means of...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-14-1458

    authors: Unger J,Lohscheller J,Reiter M,Eder K,Betz CS,Schuster M

    更新日期:2015-01-01 00:00:00

  • Enhanced activation of epidermal growth factor receptor caused by tumor-derived E-cadherin mutations.

    abstract::Mutations of the tumor suppressor E-cadherin and overexpression of the receptor tyrosine kinase epidermal growth factor receptor (EGFR) are among the most frequent genetic alterations associated with diffuse-type gastric carcinoma. Accumulating evidence suggests a functional relationship between E-cadherin and EGFR th...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-1588

    authors: Bremm A,Walch A,Fuchs M,Mages J,Duyster J,Keller G,Hermannstädter C,Becker KF,Rauser S,Langer R,von Weyhern CH,Höfler H,Luber B

    更新日期:2008-02-01 00:00:00

  • Recombinant human interleukin 4 has antiproliferative activity on human tumor cell lines derived from epithelial and nonepithelial histologies.

    abstract::Interleukin 4, a T cell-derived 20-kDa glycoprotein, plays an important role in regulating the immune response of B cells, T cells, and macrophages against infections and malignant cells. For this reason recombinant human interleukin 4 (rhIL-4) has entered early clinical trials in cancer patients. In the present study...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Topp MS,Papadimitriou CA,Eitelbach F,Koenigsmann M,Oelmann E,Koehler B,Oberberg D,Reufi B,Stein H,Thiel E

    更新日期:1995-05-15 00:00:00

  • DNA mismatch binding defects, DNA damage tolerance, and mutator phenotypes in human colorectal carcinoma cell lines.

    abstract::DNA mismatch binding in vitro, resistance to DNA methylation damage, and spontaneous mutation rates were examined in human colorectal adenocarcinoma cell lines. Of 11 cell lines, 3 (DLD1, HCT15, and LoVo) were defective in mismatch binding. All three lines had a mutator phenotype. These properties indicate that DLD1 a...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Branch P,Hampson R,Karran P

    更新日期:1995-06-01 00:00:00

  • Molecular identification of GD3 as a suppressor of the innate immune response in ovarian cancer.

    abstract::Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-11-2695

    authors: Webb TJ,Li X,Giuntoli RL 2nd,Lopez PH,Heuser C,Schnaar RL,Tsuji M,Kurts C,Oelke M,Schneck JP

    更新日期:2012-08-01 00:00:00

  • Peripheral benzodiazepine receptor ligands reverse apoptosis resistance of cancer cells in vitro and in vivo.

    abstract::The mitochondrial peripheral benzodiazepine receptor (mPBR) is involved in a functional structure designated as the permeability transition pore, which controls apoptosis. Binding of Fas/APO-1/CD95 triggers a prototypic apoptosis-inducing pathway. Using four different human tumor cell lines (T-cell Jurkat, neuroblasto...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Decaudin D,Castedo M,Nemati F,Beurdeley-Thomas A,De Pinieux G,Caron A,Pouillart P,Wijdenes J,Rouillard D,Kroemer G,Poupon MF

    更新日期:2002-03-01 00:00:00

  • Relationship of radioantibody localization and cell viability in a xenografted human cancer model as measured by whole-body autoradiography.

    abstract::The simultaneous distribution of monoclonal 131I-labeled anti-carcinoembryonic antigen (CEA) immunoglobulin (IgG) (NP-2) or 131I-labeled irrelevant myeloma IgG (Ag8) and [3H]thymidine was studied in hamsters bearing transplants of the GW-39 human colon carcinoma by qualitative double-tracer whole-body autoradiography....

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Fand I,Sharkey RM,Primus FJ,Cohen SA,Goldenberg DM

    更新日期:1987-04-15 00:00:00