Netrin-1 and Its Receptor DCC Are Causally Implicated in Melanoma Progression.

Abstract:

:Deleted in colorectal cancer (DCC), the receptor for the multifunctional cue netrin-1, acts as a tumor suppressor in intestinal cancer and lung metastasis by triggering cancer cell death when netrin-1 is lowly expressed. Recent genomic data highlighted that DCC is the third most frequently mutated gene in melanoma; we therefore investigated whether DCC could act as a melanoma tumor suppressor. Reexpressing DCC in human melanoma cell lines promoted tumor cell death and tumor growth inhibition in xenograft mouse models. Genetic silencing of DCC prodeath activity in a BRAFV600E mouse model increased the proportion of mice with melanoma, further supporting that DCC is a melanoma tumor suppressor. Netrin-1 expression was elevated in melanoma compared with benign melanocytic lesions. Upregulation of netrin-1 in the skin cells of a BRAFV600E-mutated murine model reduced cancer cell death and promoted melanoma progression. Therapeutic antibody blockade of netrin-1 combined with dacarbazine increased overall survival in several mouse melanoma models. Together, these data support that interfering with netrin-1 could be a viable therapeutic approach in patients with netrin-1-expressing melanoma. SIGNIFICANCE: Netrin-1 and its receptor DCC regulate melanoma progression, suggesting therapeutic targeting of this signaling axis as a viable option for melanoma treatment.

journal_name

Cancer Res

journal_title

Cancer research

authors

Boussouar A,Tortereau A,Manceau A,Paradisi A,Gadot N,Vial J,Neves D,Larue L,Battistella M,Leboeuf C,Lebbé C,Janin A,Mehlen P

doi

10.1158/0008-5472.CAN-18-1590

subject

Has Abstract

pub_date

2020-02-15 00:00:00

pages

747-756

issue

4

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-18-1590

journal_volume

80

pub_type

杂志文章
  • Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis.

    abstract::Epidermal growth factor receptor (EGFR) is a known diagnostic and, although controversial, prognostic marker of human glioblastoma multiforme (GBM). However, its functional role and biological significance in GBM remain elusive. Here, we show that multiple GBM cell subpopulations could be purified from the specimens o...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-10-2353

    authors: Mazzoleni S,Politi LS,Pala M,Cominelli M,Franzin A,Sergi Sergi L,Falini A,De Palma M,Bulfone A,Poliani PL,Galli R

    更新日期:2010-10-01 00:00:00

  • Preclinical antilymphoma activity of a humanized anti-CD40 monoclonal antibody, SGN-40.

    abstract::SGN-40 is a humanized IgG1 antihuman CD40 that is currently in a phase I clinical trial for the treatment of multiple myeloma. As surface CD40 expression on B-lineage cells is maintained from pro-B cells to plasma cells, SGN-40 may be applicable to treatment of other B-cell neoplasias, including non-Hodgkin's lymphoma...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-0095

    authors: Law CL,Gordon KA,Collier J,Klussman K,McEarchern JA,Cerveny CG,Mixan BJ,Lee WP,Lin Z,Valdez P,Wahl AF,Grewal IS

    更新日期:2005-09-15 00:00:00

  • Anthracycline immunoconjugates prepared by a site-specific linkage via an amino-dextran intermediate carrier.

    abstract::Anthracycline, either daunomycin or doxorubicin, was site specifically attached to the carbohydrate moiety of a monoclonal anticarcinoembryonic antigen antibody by using amino-dextran as the intermediate carrier. The reaction resulted in an immunoconjugate that contains approximately 20 to 25 molecules of drug per mol...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Shih LB,Goldenberg DM,Xuan H,Lu H,Sharkey RM,Hall TC

    更新日期:1991-08-15 00:00:00

  • Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%.

    abstract::It is estimated that familial aggregation and genetic susceptibility play a role in as many as 10% of pancreatic ductal adenocarcinomas. To investigate the role of germ-line mutations in the etiology of pancreatic cancer, we have analyzed samples from patients with pancreatic cancer enrolled in the NFPTR for mutations...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Murphy KM,Brune KA,Griffin C,Sollenberger JE,Petersen GM,Bansal R,Hruban RH,Kern SE

    更新日期:2002-07-01 00:00:00

  • Human cervical cancer as a venereal disease.

    abstract::The operation of venereal factors in human cervical cancer is suggested by demographic and epidemiological data. Recent evidence supporting the genital herpesvirus hypothesis is consistent with this notion. A controlled epidemiological investigation has been undertaken on the role of the male coital partner in cervica...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:

    authors: Kessler II

    更新日期:1976-02-01 00:00:00

  • A range of cancers is associated with the rs6983267 marker on chromosome 8.

    abstract::Several genome-wide searches for common cancers have lead to the identification of a small number of loci that harbor low-risk cancer susceptibility markers. One marker, rs6983267 on chromosome 8q24, has been linked to both colon and prostate cancer, and is therefore a good candidate for a multicancer susceptibility m...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-1838

    authors: Wokolorczyk D,Gliniewicz B,Sikorski A,Zlowocka E,Masojc B,Debniak T,Matyjasik J,Mierzejewski M,Medrek K,Oszutowska D,Suchy J,Gronwald J,Teodorczyk U,Huzarski T,Byrski T,Jakubowska A,Górski B,van de Wetering T,Walczak

    更新日期:2008-12-01 00:00:00

  • BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner.

    abstract::Mouse polyclonal antibodies, raised against three regions of the human BRCA1 protein, were characterized and revealed BRCA1 as a 220-kDa nuclear phosphoprotein in normal cells. All three antisera recognize both in vitro-translated and recombinant, baculovirus-derived BRCA1, which co-migrate with BRCA1 from the human b...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Chen Y,Farmer AA,Chen CF,Jones DC,Chen PL,Lee WH

    更新日期:1996-07-15 00:00:00

  • Plasminogen activator and inhibitor activity in human glioma cells and modulation by sodium butyrate.

    abstract::The activity of the serine protease plasminogen activator (PA), which correlates with tumorigenicity and metastatic capacity, was examined using the 125I-labeled fibrin plate assay in cell extracts from four human glioma lines as a function of growth in vitro. Cell-associated inhibitory activity to plasmin and urokina...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gross JL,Behrens DL,Mullins DE,Kornblith PL,Dexter DL

    更新日期:1988-01-15 00:00:00

  • Enhancement of metastatic potential by gamma-interferon.

    abstract::Preincubation of murine colon 26 colon adenocarcinoma cells with gamma-interferon (IFN-gamma), but not alpha-interferon, produced a significant increase in experimental pulmonary metastases in syngeneic BALB/c and T-cell-deficient BALB/c nude mice. The enhancement was seen after as little as 1 h of exposure to 1 unit/...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kelly SA,Gschmeissner S,East N,Balkwill FR

    更新日期:1991-08-01 00:00:00

  • Bicarbonate increases tumor pH and inhibits spontaneous metastases.

    abstract::The external pH of solid tumors is acidic as a consequence of increased metabolism of glucose and poor perfusion. Acid pH has been shown to stimulate tumor cell invasion and metastasis in vitro and in cells before tail vein injection in vivo. The present study investigates whether inhibition of this tumor acidity will...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-5575

    authors: Robey IF,Baggett BK,Kirkpatrick ND,Roe DJ,Dosescu J,Sloane BF,Hashim AI,Morse DL,Raghunand N,Gatenby RA,Gillies RJ

    更新日期:2009-03-15 00:00:00

  • Cell surface characteristics of an allotransplantable TA3 ascites subline resulting from a process of immunoselection.

    abstract::Comparison of the cell surface characteristics of the parental strain-specific TA3-St ascites cell (I) of the strain A mouse and the more allotransplantable TA3-St/ticol ascites cell (II), immunoselected for reduced absorption of anti-H-2a antibody from Cell I, revealed the following. Cell II, like Cell I, possessed n...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Codington JF,Das HR,Dalianis T,Klein G,Miller SC,Silber C,Lampert LA,Darby DM,Jeanloz RW

    更新日期:1983-09-01 00:00:00

  • Celastraceae sesquiterpenes as a new class of modulators that bind specifically to human P-glycoprotein and reverse cellular multidrug resistance.

    abstract::Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one mechanism by which tumor cells may develop multidrug resistance (MDR), preventing the successful chemotherapeutic treatment of cancer. Sesquiterpenes from Celastraceae family are natural compounds shown previously to reverse MDR in several ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-1005

    authors: Muñoz-Martínez F,Lu P,Cortés-Selva F,Pérez-Victoria JM,Jiménez IA,Ravelo AG,Sharom FJ,Gamarro F,Castanys S

    更新日期:2004-10-01 00:00:00

  • Effect of dietary 2(3)-tert-butyl-4-hydroxyanisole on the metabolism and action of estradiol and estrone in female CD-1 mice.

    abstract::Administration of 0.75% 2(3)-tert-butyl-4-hydroxyanisole (BHA) in AIN-76A diet to female CD-1 mice for 3 weeks increased liver microsomal glucuronidation of estradiol, estrone, 4-aminophenol, and 4-nitrophenol by 103, 187, 162, and 92%, respectively (at pH 7.4). The overall rate of NADPH-dependent metabolism of estrad...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Zhu BT,Lech J,Rosen RT,Conney AH

    更新日期:1997-06-15 00:00:00

  • Cloning and characterization of human adenosine 5'-triphosphate-binding cassette, sub-family A, transporter 2 (ABCA2).

    abstract::We have isolated the full-length cDNA for human ATP-binding cassette, sub-family A, member 2 transporter (ABCA2). The ORF of this cDNA encodes a protein consisting of 2436 amino acids with apparent molecular weight of M(r) 270,000. Accordingly, ABCA2 is the largest known mammalian ABC transporter described thus far. A...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Vulevic B,Chen Z,Boyd JT,Davis W Jr,Walsh ES,Belinsky MG,Tew KD

    更新日期:2001-04-15 00:00:00

  • p53 mutations in basal cell carcinomas.

    abstract::Genomic DNA from 14 basal cell carcinoma biopsies was screened for the presence of mutations in the p53 gene, using the polymerase chain reaction followed by direct DNA sequencing. Heterozygous mutations were detected in 7 of 14 (50%) samples investigated. All mutations were G:C-A:T transitions, and five (71%) of thes...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Rady P,Scinicariello F,Wagner RF Jr,Tyring SK

    更新日期:1992-07-01 00:00:00

  • Lung cancer detection and prevention: evidence for an interaction between smoking and genetic predisposition.

    abstract::The initiation and promotion of cancer is thought to result from a series of genetic mutations, some of which may be inherited. Our analysis of 337 lung cancer families suggested that, after allowing for an individual's pack-years of tobacco use, the pattern of disease was best explained by Mendelian codominant inheri...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Sellers TA,Potter JD,Bailey-Wilson JE,Rich SS,Rothschild H,Elston RC

    更新日期:1992-05-01 00:00:00

  • Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger RNA targets.

    abstract::Despite their extensive clinical and pathologic heterogeneity, all malignant germ cell tumors (GCT) are thought to originate from primordial germ cells. However, no common biological abnormalities have been identified to date. We profiled 615 microRNAs (miRNA) in pediatric malignant GCTs, controls, and GCT cell lines ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-3301

    authors: Palmer RD,Murray MJ,Saini HK,van Dongen S,Abreu-Goodger C,Muralidhar B,Pett MR,Thornton CM,Nicholson JC,Enright AJ,Coleman N,Children's Cancer and Leukaemia Group.

    更新日期:2010-04-01 00:00:00

  • Downregulation of microRNA-515-5p by the estrogen receptor modulates sphingosine kinase 1 and breast cancer cell proliferation.

    abstract::Sphingosine kinase 1 (SK1) plays an important role in estrogen-dependent breast tumorigenesis, but its regulation is poorly understood. A subset of microRNAs (miRNA, miR) is regulated by estrogen and contributes to cellular proliferation and cancer progression. Here, we describe that miR-515-5p is transcriptionally re...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-13-0158

    authors: Pinho FG,Frampton AE,Nunes J,Krell J,Alshaker H,Jacob J,Pellegrino L,Roca-Alonso L,de Giorgio A,Harding V,Waxman J,Stebbing J,Pchejetski D,Castellano L

    更新日期:2013-10-01 00:00:00

  • Transcriptional repression of the D-type cyclin-dependent kinase inhibitor p16 by the retinoblastoma susceptibility gene product pRb.

    abstract::Progression of the eukaryotic cell division cycle is regulated by a series of structurally related serine/threonine protein kinases known as cyclin-dependent kinases (CDKs). The D-type cyclin-dependent kinases, CDK4 and CDK6, have been strongly implicated in the control of G1 progression and the phosphorylation of the...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Li Y,Nichols MA,Shay JW,Xiong Y

    更新日期:1994-12-01 00:00:00

  • IL6 Promotes a STAT3-PRL3 Feedforward Loop via SHP2 Repression in Multiple Myeloma.

    abstract::Overexpression of PRL-3, an oncogenic phosphatase, was identified as a novel cluster in patients with newly diagnosed multiple myeloma. However, the regulation and oncogenic activities of PRL-3 in multiple myeloma warrant further investigation. Here, we report that IL6 activates STAT3, which acts as a direct transcrip...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-0343

    authors: Chong PSY,Zhou J,Lim JSL,Hee YT,Chooi JY,Chung TH,Tan ZT,Zeng Q,Waller DD,Sebag M,Chng WJ

    更新日期:2019-09-15 00:00:00

  • Hybrid selection of transcribed sequences from microdissected DNA: isolation of genes within amplified region at 20q11-q13.2 in breast cancer.

    abstract::In human breast carcinomas, increased copy number of DNA sequences derived from the long arm of chromosome 20 (20q) has been commonly observed by both chromosome microdissection and comparative genomic hybridization. This chromosomal region is likely to contain one or more genes that are the biological targets of this...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Guan XY,Xu J,Anzick SL,Zhang H,Trent JM,Meltzer PS

    更新日期:1996-08-01 00:00:00

  • Hyperplastic gastric tumors with spasmolytic polypeptide-expressing metaplasia caused by tumor necrosis factor-alpha-dependent inflammation in cyclooxygenase-2/microsomal prostaglandin E synthase-1 transgenic mice.

    abstract::We showed recently that Helicobacter infection induces expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in the mouse stomach, and that transgenic mice expressing both cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (K19-C2mE mice) develop hyperplastic gastric tumors with inflammatory...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-1936

    authors: Oshima M,Oshima H,Matsunaga A,Taketo MM

    更新日期:2005-10-15 00:00:00

  • Cancer stem cells are enriched in the side population cells in a mouse model of glioma.

    abstract::The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characterist...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-0786

    authors: Harris MA,Yang H,Low BE,Mukherjee J,Guha A,Bronson RT,Shultz LD,Israel MA,Yun K

    更新日期:2008-12-15 00:00:00

  • Generation of primary tumor-specific cytotoxic T lymphocytes from autologous and human lymphocyte antigen class I-matched allogeneic peripheral blood lymphocytes by B7 gene-modified melanoma cells.

    abstract::Expression of B7.1 costimulatory molecules on tumor cells has been shown to elicit antitumor immunity in mice. In the present study, we have developed a human B7.1 retroviral vector system to effectively transduce human melanoma cell lines and investigated the potential role of B7.1 in the generation of tumor-specific...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yang S,Darrow TL,Seigler HF

    更新日期:1997-04-15 00:00:00

  • Interspecies scaling of the pharmacokinetics of N-nitrosodimethylamine.

    abstract::The pharmacokinetics of N-nitrosodimethylamine was studied in patas monkeys following i.v. doses of 0.5, 1.0, and 5.0 mg/kg and a p.o. dose of 1.0 mg/kg, and in Swiss mice at i.v. doses of 1.0 and 2.0 mg/kg. In the patas monkey the pharmacokinetics was linear over the i.v. dose range studied. The mean clearance (Cl), ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gombar CT,Harrington GW,Pylypiw HM Jr,Anderson LM,Palmer AE,Rice JM,Magee PN,Burak ES

    更新日期:1990-07-15 00:00:00

  • Neoadjuvant-Intensive Androgen Deprivation Therapy Selects for Prostate Tumor Foci with Diverse Subclonal Oncogenic Alterations.

    abstract::Primary prostate cancer can have extensive microheterogeneity, but its contribution to the later emergence of metastatic castration-resistant prostate cancer (mCRPC) remains unclear. In this study, we microdissected residual prostate cancer foci in radical prostatectomies from 18 men treated with neoadjuvant-intensive...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-18-0610

    authors: Sowalsky AG,Ye H,Bhasin M,Van Allen EM,Loda M,Lis RT,Montaser-Kouhsari L,Calagua C,Ma F,Russo JW,Schaefer RJ,Voznesensky OS,Zhang Z,Bubley GJ,Montgomery B,Mostaghel EA,Nelson PS,Taplin ME,Balk SP

    更新日期:2018-08-15 00:00:00

  • Antitumor effects of SMANCS on rat mammary tumor induced by 7,12-dimethylbenz[a]anthracene.

    abstract::We previously found that a high-molecular-weight anticancer agent, polystyrene-co-maleic acid conjugated neocarzinostatin (SMANCS), in which two chains of styrene/maleic acid copolymer are conjugated to the anticancer protein neocarzinostatin (NCS), accumulated more selectively in tumor tissue than in normal tissue an...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kimoto A,Konno T,Kawaguchi T,Miyauchi Y,Maeda H

    更新日期:1992-02-15 00:00:00

  • Induction of medulloblastomas in mice by sonic hedgehog, independent of Gli1.

    abstract::The Sonic hedgehog (Shh) signaling pathway plays a critical role in normal cerebellar development and has been implicated in medulloblastomas, common malignant childhood tumors of the cerebellum. To test whether Shh mis-expression is sufficient for medulloblastoma formation, we used ultrasound biomicroscopy-guided in ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Weiner HL,Bakst R,Hurlbert MS,Ruggiero J,Ahn E,Lee WS,Stephen D,Zagzag D,Joyner AL,Turnbull DH

    更新日期:2002-11-15 00:00:00

  • Suppressive effect of basic fibroblast growth factor on transendothelial emigration of CD4(+) T-lymphocyte.

    abstract::The effect of basic fibroblast growth factor (b-FGF), one of the commonest angiogenic factors in various cancer types, on lymphocyte adhesion and transmigration across the endothelial cell monolayer was investigated using human umbilical vein-derived endothelial cells (HUVEC) and type I collagen gel. Forty-eight h exp...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kitayama J,Nagawa H,Yasuhara H,Tsuno N,Kimura W,Shibata Y,Muto T

    更新日期:1994-09-01 00:00:00

  • A syngeneic variance library for functional annotation of human variation: application to BRCA2.

    abstract::The enormous scope of natural human genetic variation is now becoming defined. To accurately annotate these variants, and to identify those with clinical importance, is often difficult to assess through functional assays. We explored systematic annotation by using homologous recombination to modify a native gene in he...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-6189

    authors: Hucl T,Rago C,Gallmeier E,Brody JR,Gorospe M,Kern SE

    更新日期:2008-07-01 00:00:00