The Notch signaling pathway as a mediator of tumor survival.

Abstract:

:The Notch signaling pathway is evolutionarily conserved and responsible for cell fate determination in the developing embryo and mature tissue. At the molecular level, ligand binding activates Notch signaling by liberating the Notch intracellular domain, which then translocates into the nucleus and activates gene transcription. Despite the elegant simplicity of this pathway, which lacks secondary messengers or a signaling cascade, Notch regulates gene expression in a highly context- and cell-type-dependent manner. Notch signaling is frequently dysregulated, most commonly by overactivation, across many cancers and confers a survival advantage on tumors, leading to poorer outcomes for patients. Recent studies demonstrate how Notch signaling increases tumor cell proliferation and provide evidence that active Notch signaling maintains the cancer stem-cell pool, induces epithelial-mesenchymal transition and promotes chemoresistance. These studies imply that pharmacological inhibition of Notch signaling may refine control of cancer therapy and improve patient survival. Gamma secretase inhibitors (GSIs) are drugs that inhibit Notch signaling and may be successful in controlling cancer cell growth in conjunction with standard chemotherapy, but substantial side effects have hampered their widespread use. Recent efforts have been aimed at the development of antibodies against specific Notch receptors and ligands with the hope of limiting side effects while providing the same therapeutic benefit as GSIs. Together, studies characterizing Notch signaling and modulation have offered hope that refined methods targeting Notch may become powerful tools in anticancer therapeutics.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Capaccione KM,Pine SR

doi

10.1093/carcin/bgt127

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

1420-30

issue

7

eissn

0143-3334

issn

1460-2180

pii

bgt127

journal_volume

34

pub_type

杂志文章,评审
  • Activation of autophagy in mesenchymal stem cells provides tumor stromal support.

    abstract::Recent studies have implicated multipotential mesenchymal stem cells (MSCs) as an aid to breast cancer cell proliferation and metastasis, partly as a result of the MSCs secretome. As the tumor gets beyond 2 mm in diameter, the stromal cells could undergo starvation due to the lack of sufficient nutrients in solid tumo...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr029

    authors: Sanchez CG,Penfornis P,Oskowitz AZ,Boonjindasup AG,Cai DZ,Dhule SS,Rowan BG,Kelekar A,Krause DS,Pochampally RR

    更新日期:2011-07-01 00:00:00

  • Comparison of mutagenesis by O6-methyl- and O6-ethylguanine and O4-methylthymine in Escherichia coli using double-stranded and gapped plasmids.

    abstract::To compare mutagenesis by O6-methylguanine (m6G), O4-methylthymine (m4T) and O6-ethylguanine (e6G), and assess their genotoxicity in Escherichia coli, double-stranded and gapped plasmids were constructed containing a single m6G, e6G or m4T in the initiation codon (ATG) of a lacZ' gene. Modified base induced mutations ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/19.3.457

    authors: Pauly GT,Hughes SH,Moschel RC

    更新日期:1998-03-01 00:00:00

  • Mutagenicity and synthesis of alpha-substituted N-nitrosamines: derivatives with dithiocarbamic acid.

    abstract::Disulfiram (DSF) can considerably alter the organotropy of chemical carcinogens. For N-nitrosodimethylamine and for N-nitrosodiethylamine the organotropy is shifted from the liver to the nasal cavity or the oesophagus, respectively. Whereas the influence of DSF or its metabolites on enzyme systems has been studied, li...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.5.563

    authors: Pool BL,Bertram B,Wiessler M

    更新日期:1982-01-01 00:00:00

  • Resistance of Copenhagen rats to chemical induction of glutathione S-transferase 7-7-positive liver foci.

    abstract::Copenhagen (Cop) rats are completely resistant to the chemical induction of mammary adenocarcinomas, but their susceptibility to hepatocarcinogenesis is virtually unknown. Rat liver is a well-characterized and easily manipulated tissue in which to study carcinogenesis. Therefore, if Cop rats are resistant to hepatocar...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/18.9.1745

    authors: Wood GA,Korkola JE,Lee VM,Sarma DS,Archer MC

    更新日期:1997-09-01 00:00:00

  • Microsome-mediated alkylation of rat liver initiator tRNA by 3,3-dimethyl-1-phenyltriazene and its ring-chlorinated derivatives.

    abstract::3,3-[3H]Dimethyl-1-phenyltriazene, 1-(4-chlorophenyl)-3,3-[3H]dimethyltriazene and 3,3-[3H]dimethyl-1-(2,4,6-trichlorophenyl)-triazene methylate initiator tRNA in vitro only after pre-incubation with microsomal enzymes and NADPH. The finding confirms that procarcinogenic dialkyl aryltriazenes must be enzymatically con...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/6.7.995

    authors: Hradec J,Kolar GF

    更新日期:1985-07-01 00:00:00

  • Association of genetic variants in CHEK2 with oesophageal squamous cell carcinoma in the South African Black population.

    abstract::Oesophageal squamous cell carcinoma (OSCC) has a high incidence in southern Africa and a poor prognosis. Limited information is available on the contribution of genetic variants in susceptibility to OSCC in this region. However, recent genome-wide association studies have identified multiple susceptibility loci in Asi...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgz026

    authors: Chen WC,Bye H,Matejcic M,Amar A,Govender D,Khew YW,Beynon V,Kerr R,Singh E,Prescott NJ,Lewis CM,Babb de Villiers C,Parker MI,Mathew CG

    更新日期:2019-06-10 00:00:00

  • Tumor progression and metastasis.

    abstract::It is now widely accepted that cancer is attributed to the accumulation of genetic alterations in cells. Thus, to understand the molecular mechanisms of cancer metastasis, it is indispensable to identify the genes whose alterations accumulate during cancer progression as well as the genes whose expression is responsib...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/21.3.497

    authors: Yokota J

    更新日期:2000-03-01 00:00:00

  • The R438W polymorphism of human DNA polymerase lambda triggers cellular sensitivity to camptothecin by compromising the homologous recombination repair pathway.

    abstract::The human DNA polymerase lambda (Polλ) is a DNA repair polymerase, which is believed not only to play a role in base excision repair but also to contribute to DNA double-strand break repair by non-homologous end joining. We described here that cellular expression of the recently described natural polymorphic variant o...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgq166

    authors: Capp JP,Boudsocq F,Bergoglio V,Trouche D,Cazaux C,Blanco L,Hoffmann JS,Canitrot Y

    更新日期:2010-10-01 00:00:00

  • Genomic pattern of intratumor heterogeneity predicts the risk of progression in early stage diffuse large B-cell lymphoma.

    abstract::Intratumor heterogeneity (ITH) plays an important role in tumor development, metastases, recurrence and has impact on clinical diagnosis, therapeutic responses. In this study, we used mutant-allele tumor heterogeneity (MATH) through whole-exome sequencing data to evaluate ITH in early stage diffuse large B-cell lympho...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgz068

    authors: Wang Y,Feng W,Liu P

    更新日期:2019-11-25 00:00:00

  • Synthetic D-amino acid peptide inhibits tumor cell motility on laminin-5.

    abstract::Cell motility is partially dependent on interactions between the integrins and the extracellular matrix. Our previous studies have identified synthetic D-amino acid cell adhesion peptides using a combinatorial screening approach. In this study, we demonstrate that HYD1 (kikmviswkg) completely blocks random haptotactic...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgl005

    authors: Sroka TC,Pennington ME,Cress AE

    更新日期:2006-09-01 00:00:00

  • Long-term tracking of hepatitis B viral load and the relationship with risk for hepatocellular carcinoma in men.

    abstract::Little is known about the longitudinal course of hepatitis B virus (HBV) load and its relationship with the development of hepatocellular carcinoma (HCC). We conducted a case-cohort study nested within a cohort of 2874 HBV surface antigen-positive male Taiwanese government employees aged 30 years or older. HBV genotyp...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgm252

    authors: Wu CF,Yu MW,Lin CL,Liu CJ,Shih WL,Tsai KS,Chen CJ

    更新日期:2008-01-01 00:00:00

  • Rapid induction of uterine tumors with p53 point mutations in heterozygous p53-deficient CBA mice given a single intraperitoneal administration of N-ethyl-N-nitrosourea.

    abstract::To investigate the sensitivity of heterozygous p53-deficient CBA mice to carcinogens, 20 female mice [p53(+/-)] and 20 wild-type littermates [p53(+/+)] were given an intraperitoneal injection of 120 mg/kg body wt of N-ethyl-N-nitrosourea (ENU) and were maintained without any other treatment for a further 26 weeks. His...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/21.5.1039

    authors: Mitsumori K,Onodera H,Shimo T,Yasuhara K,Takagi H,Koujitani T,Hirose M,Maruyama C,Wakana S

    更新日期:2000-05-01 00:00:00

  • Nafenopin-induced rat liver peroxisome proliferation reduces DNA methylation by N-nitrosodimethylamine in vivo.

    abstract::The hypolipidaemic drug nafenopin (NAF) has been shown to enhance the hepatocarcinogenic effect of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine in rats. We have investigated whether the NAF-induced peroxisome proliferation in hepatocytes interferes with NDMA's metabolism and interaction with DNA. Adult male...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/6.9.1309

    authors: Wiestler OD,Schmerold I,Fringes B,Volk B,Kleihues P

    更新日期:1985-09-01 00:00:00

  • gamma-Glutamyltranspeptidase-positive rat hepatocytes are protected from GSH depletion, oxidative stress and reversible alterations of collagen receptors.

    abstract::The aim of this study has been to define cytotoxic mechanisms that may cause clonal expansion in the liver of pre-carcinogenic cells. An in vitro model, which has been described previously, was used. Hepatocytes were isolated from carcinogen-treated rats and a high proportion of the cells were gamma-glutamyltranspepti...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.1.69

    authors: Stenius U,Rubin K,Gullberg D,Högberg J

    更新日期:1990-01-01 00:00:00

  • Population-specific genetic associations with oesophageal squamous cell carcinoma in South Africa.

    abstract::Genetic variants in multiple cellular pathways have been associated with an altered risk of oesophageal cancer. In this study, eight genes previously associated with an altered risk of oesophageal squamous cell carcinoma (OSCC) in European or Asian populations were investigated in two South African populations. We gen...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr211

    authors: Bye H,Prescott NJ,Matejcic M,Rose E,Lewis CM,Parker MI,Mathew CG

    更新日期:2011-12-01 00:00:00

  • Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice.

    abstract::Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-caten...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr293

    authors: Bi X,Pohl NM,Qian Z,Yang GR,Gou Y,Guzman G,Kajdacsy-Balla A,Iozzo RV,Yang W

    更新日期:2012-02-01 00:00:00

  • Apoptosis by dietary factors: the suicide solution for delaying cancer growth.

    abstract::Apoptosis, a form of programmed cell death, plays a fundamental role in the maintenance of tissues and organ systems by providing a controlled cell deletion to balanced cell proliferation. The last decade has witnessed an exponential increase in the number of studies investigating how different components of the diet ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/bgl243

    authors: Khan N,Afaq F,Mukhtar H

    更新日期:2007-02-01 00:00:00

  • Tobacco smoke induces CYP1B1 in the aerodigestive tract.

    abstract::Several members of the P450 family, including cytochrome P450 1B1 (CYP1B1), can convert tobacco smoke (TS) procarcinogens, including benzo[a]pyrene (B[a]P), to carcinogenic intermediates. In this study we investigated the effects of TS condensate and B[a]P on the expression of CYP1B1 in vitro and in vivo. CYP1B1 mRNA ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgh243

    authors: Port JL,Yamaguchi K,Du B,De Lorenzo M,Chang M,Heerdt PM,Kopelovich L,Marcus CB,Altorki NK,Subbaramaiah K,Dannenberg AJ

    更新日期:2004-11-01 00:00:00

  • Age-dependent odontogenic lesions in rats after a single i.p. injection of N-nitroso-N-methylurea.

    abstract::The development of a variety of odontogenic lesions was elicited by a single i.p. injection of N-nitroso-N-methylurea (NMU) at a dose of 150 mg/kg body weight. A total of 190 male Wistar/Furth rats were used in this study. The odontogenic lesions appeared macroscopically, mainly as supernumerary lower incisors, 88 +/-...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/4.9.1085

    authors: Smulow JB,Konstantinidis A,Sonnenschein C

    更新日期:1983-09-01 00:00:00

  • The effect of the format of administration and the total dose of phenobarbital on altered hepatic foci following initiation in female rats with diethylnitrosamine.

    abstract::The effect of changing the format of administration as well as the total dose of the promoting agent phenobarbital (PB) on the development of altered hepatic foci (AHF) was determined in an initiation-promotion protocol with female rats fed the purified AIN-76 diet. Effects on the total number of AHF and the volume pe...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.6.1009

    authors: Xu YD,Dragan YP,Young T,Pitot HC

    更新日期:1991-06-01 00:00:00

  • Expression of CYP1B1 but not CYP1A1 by primary cultured human mammary stromal fibroblasts constitutively and in response to dioxin exposure: role of the Ah receptor.

    abstract::The expression of CYP1B1 in human mammary fibroblasts (HMFs) was characterized as a potential modulator of their individual function as well as effects on adjacent mammary epithelia. We have used these characteristics to explore the diversity of fibroblast cells isolated from reduction mammoplasty patients and from di...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/19.8.1437

    authors: Eltom SE,Larsen MC,Jefcoate CR

    更新日期:1998-08-01 00:00:00

  • Metabolism of the cis and trans isomers of N-nitroso-2,6-dimethylmorpholine and their deuterated analogs by liver microsomes of rat and hamster.

    abstract::Liver microsomes from male Syrian golden hamsters and Sprague Dawley rats metabolize the cis and trans isomers of N-nitroso-2,6-dimethylmorpholine (NNDM) to N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) as the major product detectable by h.p.l.c. The rates of total metabolism are similar for both the cis and tr...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/5.8.1009

    authors: Kokkinakis D,Hollenberg PF,Scarpelli DG

    更新日期:1984-08-01 00:00:00

  • Effects of arsenic on telomerase and telomeres in relation to cell proliferation and apoptosis in human keratinocytes and leukemia cells in vitro.

    abstract::Telomeres are critical in maintaining chromosome and genomic stability. Arsenic, a human carcinogen as well as an anticancer agent, is known for its clastogenicity. To better understand molecular mechanisms of arsenic actions, we investigated arsenite effects on telomere and telomerase and determined cell growth and a...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgg141

    authors: Zhang TC,Schmitt MT,Mumford JL

    更新日期:2003-11-01 00:00:00

  • Promotion, but not progression, effects of tamoxifen on uterine carcinogenesis in mice initiated with N-ethyl-N'-nitro-N-nitrosoguanidine.

    abstract::Effects of tamoxifen (TAM) on development of uterine endometrial carcinogenesis were studied in intact and ovariectomized (OVX) mice initiated with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). In experiment I, animals were implanted with cholesterol (ChL, controls) or TAM (5% w/w) and/or 17beta-oestradiol (E(2), 0.5% w...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/23.9.1549

    authors: Takahashi M,Shimomoto T,Miyajima K,Iizuka S,Watanabe T,Yoshida M,Kurokawa Y,Maekawa A

    更新日期:2002-09-01 00:00:00

  • 5-Sulfooxymethylfurfural as a possible ultimate mutagenic and carcinogenic metabolite of the Maillard reaction product, 5-hydroxymethylfurfural.

    abstract::Heat treatment of foods containing reducing sugars and amino acids during cooking or sterilization triggers a sequence of non-enzymatic reactions collectively known as the Maillard reaction. 5-Hydroxymethylfurfural (HMF), one of the major intermediate products in the Maillard reaction, has been found to possess cytoto...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.10.2375

    authors: Surh YJ,Liem A,Miller JA,Tannenbaum SR

    更新日期:1994-10-01 00:00:00

  • Increasing fish consumption does not affect genotoxicity markers in the colon in an intervention study.

    abstract::Observational studies suggest that fish consumption is associated with a decreased colorectal cancer (CRC) risk. A possible mechanism by which fish could reduce CRC risk is by decreasing colonic genotoxicity. However, concerns have also been raised over the levels of toxic compounds found in mainly oil-rich fish, whic...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1093/carcin/bgp255

    authors: Pot GK,Habermann N,Majsak-Newman G,Harvey LJ,Geelen A,Przybylska-Philips K,Nagengast FM,Witteman BJ,van de Meeberg PC,Hart AR,Schaafsma G,Hooiveld G,Glei M,Lund EK,Pool-Zobel BL,Kampman E

    更新日期:2010-06-01 00:00:00

  • Role of the beta isoform of 14-3-3 proteins in cellular proliferation and oncogenic transformation.

    abstract::The 14-3-3 proteins are associated with proto-oncogene and oncogene products. Here, we generated NIH 3T3 cells overexpressing the beta isoform of the 14-3-3 proteins (14-3-3 beta) to examine the function of this isoform in cellular proliferation and oncogenic transformation. Overexpression of 14-3-3 beta in NIH 3T3 ce...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/21.11.2073

    authors: Takihara Y,Matsuda Y,Hara J

    更新日期:2000-11-01 00:00:00

  • Vitamin E is a complete tumor promoter in mouse skin.

    abstract::The dorsal skins of 6-8 week old female SENCAR mice were initiated with a single application of 10 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) and subsequently promoted twice/week with topical applications of vitamin E (dl-alpha-tocopherol, 80 mumol/treatment). Vitamin E from two separate commercial suppliers was te...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/14.4.659

    authors: Mitchel RE,McCann R

    更新日期:1993-04-01 00:00:00

  • The use of initiated cells as a test system for the detection of inhibitors of gap junctional intercellular communication.

    abstract::The effects of five non-mutagenic carcinogens--Aroclor 1260, benzoyl peroxide (BP), phenobarbital (PB), 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 1,1'-(2,2,2-trichloroethylidene)bis[4-chlorobenzene] (DDT)--on gap junctional intercellular communication (GJIC) were tested in a cell line consisting of initiated cel...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.2.333

    authors: Jansen LA,Jongen WM

    更新日期:1996-02-01 00:00:00

  • Resveratrol protects mouse embryonic stem cells from ionizing radiation by accelerating recovery from DNA strand breakage.

    abstract::Resveratrol has elicited many provocative anticancer effects in laboratory animals and cultured cells, including reduced levels of oxidative DNA damage, inhibition of tumor initiation and progression and induction of apoptosis in tumor cells. Use of resveratrol as a cancer-preventive agent in humans will require that ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr236

    authors: Denissova NG,Nasello CM,Yeung PL,Tischfield JA,Brenneman MA

    更新日期:2012-01-01 00:00:00