Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion.

Abstract:

BACKGROUND:Epithelial-to-mesenchymal transition (EMT) is associated with decreased adhesion and acquisition of metastatic potential of breast cancer cells. Epithelial-to-mesenchymal transition is mediated, in part, by two transcription repressors, Snail and Slug, that are known to be targets of the Notch signaling pathway, and JAGGED1-induced Notch activation increases EMT. However, the events that lead to increased Notch activity during EMT of breast cancer cells are unknown. METHODS:The accumulation of hypoxia inducible factors (HIFs) under hypoxia was detected by western blot analysis, and their effects on Notch signaling were measured by an in vitro Notch reporter assay. The expression of Notch target genes under hypoxia was tested by real-time PCR. The knockdown of HIF-1alpha was mediated by retroviral delivery of shRNA. The expression of Slug and Snail under hypoxia was measured by real-time PCR. Breast cancer cell migration and invasion under hypoxia were tested with cell migration and invasion kits. RESULTS:Hypoxia increased the expression of Notch target genes such as HES1 and HEY1 in breast cancer cells, as was expression of Notch receptors and ligands. The mechanism is likely to involve the accumulation of HIF-1alpha and HIF-2alpha in these cells by hypoxia, which synergised with the Notch co-activator MAML1 in potentiating Notch activity. Hypoxia inducible factor-1alpha was found to bind to HES1 promoter under hypoxia. Knockdown of HIF-1alpha with shRNA inhibited both HES1 and HEY1 expression under hypoxia. Hypoxia increased the expression of Slug and Snail, and decreased the expression of E-cadherin, hallmarks of EMT. Notch pathway inhibition abrogated the hypoxia-mediated increase in Slug and Snail expression, as well as decreased breast cancer cell migration and invasion. CONCLUSION:Hypoxia-mediated Notch signaling may have an important role in the initiation of EMT and subsequent potential for breast cancer metastasis.

journal_name

Br J Cancer

authors

Chen J,Imanaka N,Chen J,Griffin JD

doi

10.1038/sj.bjc.6605486

subject

Has Abstract

pub_date

2010-01-19 00:00:00

pages

351-60

issue

2

eissn

0007-0920

issn

1532-1827

pii

6605486

journal_volume

102

pub_type

杂志文章
  • Phase I dose-escalation trial of irinotecan with continuous infusion 5-FU first line, in metastatic colorectal cancer.

    abstract::This single-centre phase I trial was designed to determine the maximum tolerated dose of irinotecan and the recommended dose to use in combination with a fixed dose of 5-fluorouracil (5-FU) administered as a protracted venous infusion, for the first-line treatment of metastatic colorectal cancer (CRC). Tolerability an...

    journal_title:British journal of cancer

    pub_type: 临床试验,杂志文章

    doi:10.1038/sj.bjc.6602173

    authors: Saunders MP,Hogg M,Carrington B,Sjursen AM,Allen J,Beech J,Swindell R,Valle JW

    更新日期:2004-10-18 00:00:00

  • Phase I trial and pharmacokinetics of the tubulin inhibitor 1069C85--a synthetic agent binding at the colchicine site designed to overcome multidrug resistance.

    abstract::The orally administered tubulin-binding agent 1069C85 was developed with the hope of overcoming the multidrug resistance associated with existing anti-tubulin agents, such as the vinca alkaloids. A phase I study was performed using a single oral dose every 3 weeks, administered as a suspension reconstituted in 0.1% Tw...

    journal_title:British journal of cancer

    pub_type: 临床试验,杂志文章

    doi:10.1038/bjc.1997.107

    authors: Judson I,Briasoulis E,Raynaud F,Hanwell J,Berry C,Lacey H

    更新日期:1997-01-01 00:00:00

  • Protein kinase C in human renal cell carcinomas: role in invasion and differential isoenzyme expression.

    abstract::The role of protein kinase C (PKC) in in vitro invasiveness of four different human renal cell carcinoma (RCC) cell lines of the clear cell type was investigated. Different PKC-inhibitors markedly inhibited invasiveness of the highly invasive cell lines, suggesting an invasion-promoting role of PKC in human RCC. Analy...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1054/bjoc.1999.1043

    authors: Engers R,Mrzyk S,Springer E,Fabbro D,Weissgerber G,Gernharz CD,Gabbert HE

    更新日期:2000-03-01 00:00:00

  • Early toxicity predicts long-term survival in high-grade glioma.

    abstract:BACKGROUND:Patients with high-grade gliomas are treated with surgery followed by chemoradiation. The risk factors and implications of neurological side effects are not known. METHODS:Acute and late ≥ grade 3 neurological toxicities (NTs) were analysed among 2761 patients from 14 RTOG trials accrued from 1983 to 2003. ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2011.123

    authors: Lawrence YR,Wang M,Dicker AP,Andrews D,Curran WJ Jr,Michalski JM,Souhami L,Yung WK,Mehta M

    更新日期:2011-04-26 00:00:00

  • Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation.

    abstract::Laminin-332 is major component of epithelial basement membrane, and has an important role in cell migration and tumour invasion. Recently, the phosphatidylinositol 3-kinase (PI3K) activation induced by laminin-332 during carcinogenesis or tumour invasion has been highlighted in skin squamous cell carcinoma. The expres...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6604252

    authors: Baba Y,Iyama KI,Hirashima K,Nagai Y,Yoshida N,Hayashi N,Miyanari N,Baba H

    更新日期:2008-03-11 00:00:00

  • Catalase depression in malignant liver from chickens with myeloblastosis and Marek's disease.

    abstract::In rapidly frozen livers from chickens affected with myeloblastosis and Marek's disease and from unaffected control birds there exists a strong correlation between catalase activity and catalase Electron Paramagnetic Resonance (EPR) signal intensities. The diseased chickens had activities and signals reduced to as lit...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1984.189

    authors: Williams-Smith DL,Payne LN,Wyard SJ

    更新日期:1984-09-01 00:00:00

  • Modulation of endogenous beta-tubulin isotype expression as a result of human beta(III)cDNA transfection into prostate carcinoma cells.

    abstract::Increases of individual beta tubulin isotypes in antimicrotubule drug resistant cell lines have been reported by several laboratories. We have previously described elevations in beta(III)and beta(IVa)isotypes in estramustine and paclitaxel resistant human prostate carcinoma cells. To investigate further the function o...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1054/bjoc.2001.1956

    authors: Ranganathan S,McCauley RA,Dexter DW,Hudes GR

    更新日期:2001-09-01 00:00:00

  • Response of spheroids implanted in the peritoneal cavity of mice exposed to cyclophosphamide and ionizing radiation.

    abstract::Chinese hamster V79-171B spheroids implanted in the peritoneal cavity of C3H mice were characterized as a model for evaluating the toxicity of drugs requiring metabolic activation in vivo. After 24 hours in the peritoneal cavity, spheroid cellularity and plating efficiency were not significantly decreased, and host ce...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1987.196

    authors: Olive PL

    更新日期:1987-09-01 00:00:00

  • Somatic-cell hybrids producing antibodies against CEA.

    abstract::Monoclonal antibodies to carcinoembryonic antigen (CEA) promise improved specificity for the measurement of this widely expressed human cancer antigen. A mouse monoclonal antibody binds weakly to CEA in perchloric acid extracts of tumour but strongly to CEA similarly isolated from serum, and its spectrum of cancer det...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1981.1

    authors: Rogers GT,Rawlins GA,Bagshawe KD

    更新日期:1981-01-01 00:00:00

  • Vascular endothelial growth factor-A and Poly(A) binding protein-interacting protein 2 expression in human head and neck carcinomas: correlation and prognostic significance.

    abstract::Vascular endothelial growth factor-A (VEGF-A) has been demonstrated to play an important role in tumour angiogenesis and to influence prognosis in many cancers. However its prognostic value in head and neck squamous cell carcinomas (HNSCCs) remains controversial. Therefore, we investigated the clinical relevance of VE...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6603108

    authors: Onesto C,Hannoun-Lévi JM,Chamorey E,Formento JL,Ramaioli A,Pagès G

    更新日期:2006-05-22 00:00:00

  • A study of ovarian cancer patients treated with dose-intensive chemotherapy supported with peripheral blood progenitor cells mobilised by filgrastim and cyclophosphamide.

    abstract::We have shown that large numbers of haemopoietic progenitor cells are mobilised into the blood after filgrastim [granulocyte colony-stimulating factor (G-CSF)] alone and filgrastim following cyclophosphamide chemotherapy in previously untreated patients with ovarian cancer. These cells may be used to provide safe and ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1996.637

    authors: Weaver A,Wrigley E,Watson A,Chang J,Collins CD,Jenkins B,Gill C,Pettengell R,Dexter TM,Testa NG,Crowther D

    更新日期:1996-12-01 00:00:00

  • The level of haemoglobin in anaemic cancer patients correlates positively with quality of life.

    abstract::The aim of this study was to assess the relationship between haemoglobin level and quality-of-life in anaemic cancer patients. Patients, diagnosed with one of four cancers, were recruited if their haemoglobin level was <12 g dl(-1) (female) or <13 g dl(-1) (male). The condition-specific Functional Assessment of Cancer...

    journal_title:British journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1038/sj.bjc.6600247

    authors: Lind M,Vernon C,Cruickshank D,Wilkinson P,Littlewood T,Stuart N,Jenkinson C,Grey-Amante P,Doll H,Wild D

    更新日期:2002-04-22 00:00:00

  • Candidate target genes for loss of heterozygosity on human chromosome 17q21.

    abstract::Loss of heterozygosity (LOH) on chromosome 17q21 has been detected in 30% of primary human breast tumours. The smallest common region deleted occurred in an interval between the D17S746 and D17S846 polymorphic sequences tagged sites that are located on two recombinant P1-bacteriophage clones of chromosome 17q21: 122F4...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6601848

    authors: De Marchis L,Cropp C,Sheng ZM,Bargo S,Callahan R

    更新日期:2004-06-14 00:00:00

  • Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials.

    abstract::This study evaluates the efficacy of capecitabine using data from a large, well-characterised population of patients with metastatic colorectal cancer (mCRC) treated in two identically designed phase III studies. A total of 1207 patients with previously untreated mCRC were randomised to either oral capecitabine (1250 ...

    journal_title:British journal of cancer

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1038/sj.bjc.6601676

    authors: Van Cutsem E,Hoff PM,Harper P,Bukowski RM,Cunningham D,Dufour P,Graeven U,Lokich J,Madajewicz S,Maroun JA,Marshall JL,Mitchell EP,Perez-Manga G,Rougier P,Schmiegel W,Schoelmerich J,Sobrero A,Schilsky RL

    更新日期:2004-03-22 00:00:00

  • Molecular design of hybrid tumour necrosis factor-alpha. II: The molecular size of polyethylene glycol-modified tumour necrosis factor-alpha affects its anti-tumour potency.

    abstract::To design hybrid tumour necrosis factor-alpha (TNF-alpha) applicable to systemic anti-tumour therapeutic use, we assessed the relationships among the molecular size of hybrid TNF-alpha, in vitro bioactivity and in vivo anti-tumour potency. Natural human TNF-alpha was covalently modified with polyethylene glycol (PEG) ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1996.495

    authors: Tsutsumi Y,Tsunoda S,Kamada H,Kihira T,Nakagawa S,Kaneda Y,Kanamori T,Mayumi T

    更新日期:1996-10-01 00:00:00

  • Hybrid Capture II-based human papillomavirus detection, a sensitive test to detect in routine high-grade cervical lesions: a preliminary study on 1518 women.

    abstract::Hybrid Capture II (HC-II) is a commercial human papillomavirus (HPV) detection test designed to detect 18 HPV types divided into high-risk and low-risk groups. We have tested 1647 scrapes from 1518 unselected women attending routine cytological screening by this assay for the detection of histologically proven high-gr...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6690523

    authors: Clavel C,Masure M,Bory JP,Putaud I,Mangeonjean C,Lorenzato M,Gabriel R,Quereux C,Birembaut P

    更新日期:1999-07-01 00:00:00

  • Cell killing and DNA damage by etoposide in Chinese hamster V79 monolayers and spheroids: influence of growth kinetics, growth environment and DNA packaging.

    abstract::Cells from V79 multicell spheroids must be exposed to approximately 50 times more etoposide than exponentially growing monolayers in order to produce the same amount of cell killing. A part of this difference in sensitivity is readily explained by the decrease in growth fraction of large spheroids, and by the protecti...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1993.97

    authors: Olive PL,Banáth JP,Evans HH

    更新日期:1993-03-01 00:00:00

  • Rapid nodal staging of head and neck cancer surgical specimens with flow cytometric analysis.

    abstract:BACKGROUND:Detection of metastatic spread of head and neck cancer to cervical lymph nodes is essential for optimal design of therapy. Undetected metastases lead to mortality, which can be prevented by better detection methods. METHODS:We analysed 41 lymph nodes from 19 patients with oral squamous cell carcinoma (OSCC)...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2017.408

    authors: Häyry V,Kågedal Å,Hjalmarsson E,Neves da Silva PF,Drakskog C,Margolin G,Georén SK,Munck-Wikland E,Winqvist O,Cardell LO

    更新日期:2018-02-06 00:00:00

  • Eight years of experience with vismodegib for advanced and multiple basal cell carcinoma patients in the Netherlands: a retrospective cohort study.

    abstract:BACKGROUND:Vismodegib has been used for the treatment of locally advanced basal cell carcinoma (laBCC) and metastatic BCC (mBCC) since 2011. Most efficacy and safety data are provided by clinical trials. This study evaluates the effectiveness of vismodegib for the treatment of laBCC, mBCC and basal cell nevus syndrome ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/s41416-020-01220-w

    authors: Verkouteren BJA,Wakkee M,Reyners AKL,Nelemans P,Aarts MJB,Rácz E,Terra JB,Devriese LA,Alers RJ,Kapiteijn E,van Doorn R,Bekkenk MW,Reinders MGHC,Mosterd K

    更新日期:2021-01-19 00:00:00

  • Transarterial chemo-embolisation of hepatocellular carcinoma: impact of liver function and vascular invasion.

    abstract:BACKGROUND:Transarterial chemo-embolisation (TACE) is recommended for patients with BCLC intermediate stage hepatocellular carcinoma (stage B), particularly in patients with good underlying liver function and minimal symptoms. The hepatoma arterial embolisation prognostic (HAP) score combines measures of liver function...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2016.423

    authors: Waked I,Berhane S,Toyoda H,Chan SL,Stern N,Palmer D,Tada T,Yeo W,Mo F,Bettinger D,Kirstein MM,Iñarrairaegui M,Gomaa A,Vogel A,Meyer T,Sangro B,Lai P,Kumada T,Johnson PJ

    更新日期:2017-02-14 00:00:00

  • Inhibition of cell-cycle progression by acute treatment with various degrees of hypoxia: modifications induced by low concentrations of misonidazole present during hypoxia.

    abstract::The effect on cell-cycle progression in various phases of the cell cycle caused by an acute exposure to hypoxia in absence and presence of misonidazole (MISO) was investigated. Exponentially growing and synchronized cells of the human line NHIK 3025 were exposed to different degrees of hypoxia for a short period (1.5 ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1983.271

    authors: Pettersen EO,Lindmo T

    更新日期:1983-12-01 00:00:00

  • Injection site tumours and preceding pathological changes in rats treated subcutaneously with surfactants and carcinogens.

    abstract::The sequential histological changes and neoplastic response occurring in the subcutaneous tissue of rats after injection of surfactants or carcinogens were compared. Twice weekly subcutaneous injections of the surfactants Blue VRS and Light Green SF elicited a deranged connective tissue repair with continued prolifera...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1973.28

    authors: Hooson J,Grasso P,Gangolli SD

    更新日期:1973-03-01 00:00:00

  • Serum beta-carotene and subsequent risk of cancer: results from the BUPA Study.

    abstract::In the BUPA Study, a prospective study of 22,000 men attending a screening centre in London, serum samples were collected and stored. The concentration of beta-carotene was measured in the stored serum samples from 271 men who were subsequently notified as having cancer and from 533 unaffected controls, matched for ag...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1988.97

    authors: Wald NJ,Thompson SG,Densem JW,Boreham J,Bailey A

    更新日期:1988-04-01 00:00:00

  • Reversal of glucocorticoid resistance in paediatric acute lymphoblastic leukaemia is dependent on restoring BIM expression.

    abstract:BACKGROUND:Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy. Glucocorticoids form a critical component of chemotherapy regimens and resistance to glucocorticoid therapy is predictive of poor outcome. We have previously shown that glucocorticoid resistance is associated with upregulation of t...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/s41416-020-0824-8

    authors: Toscan CE,Jing D,Mayoh C,Lock RB

    更新日期:2020-06-01 00:00:00

  • Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United Kingdom National Cancer Research Institute recommendations for monitoring.

    abstract::More women are living with and surviving breast cancer, because of improvements in breast cancer care. Trastuzumab (Herceptin) has significantly improved outcomes for women with HER2-positive tumours. Concerns about the cardiac effects of trastuzumab (which fundamentally differ from the permanent myocyte loss associat...

    journal_title:British journal of cancer

    pub_type: 杂志文章,实务指引

    doi:10.1038/sj.bjc.6604909

    authors: Jones AL,Barlow M,Barrett-Lee PJ,Canney PA,Gilmour IM,Robb SD,Plummer CJ,Wardley AM,Verrill MW

    更新日期:2009-03-10 00:00:00

  • Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation to the risk of pancreatic cancer in two Swedish population-based cohorts.

    abstract::We examined the associations of body mass index (BMI), waist circumference, a history of diabetes, and cigarette smoking with risk of pancreatic cancer among 37,147 women and 45,906 men followed up during 560,666 person-years in the Swedish Mammography Cohort and the Cohort of Swedish Men; 136 incident cases of pancre...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6602868

    authors: Larsson SC,Permert J,Håkansson N,Näslund I,Bergkvist L,Wolk A

    更新日期:2005-11-28 00:00:00

  • Ki-S1, a novel proliferative marker: flow cytometric assessment of staining in human breast carcinoma cells.

    abstract::There is considerable interest in immunohistochemical markers of proliferation which are suitable for use on routinely fixed clinical material. The novel proliferation-associated antibody Ki-S1 shows promise in this respect. In this study we have: (i) defined the pattern of Ki-S1 labelling relative to the cell cycle p...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1993.122

    authors: Camplejohn RS,Brock A,Barnes DM,Gillett C,Raikundalia B,Kreipe H,Parwaresch MR

    更新日期:1993-04-01 00:00:00

  • High levels of loss at the 17p telomere suggest the close proximity of a tumour suppressor.

    abstract::High levels of loss of distal markers on 17p13.3 in breast cancer suggested the presence within the region of at least one tumour-suppressor gene. Here we describe the derivation of two biallelic polymorphisms from the 17p telomeric yeast artificial chromosome (YAC) TYAC98. Polymerase chain reaction-restriction fragme...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1996.449

    authors: White GR,Stack M,Santibáñez-Koref M,Liscia DS,Venesio T,Wang JC,Helms C,Donis-Keller H,Betticher DC,Altermatt HJ,Hoban PR,Heighway J

    更新日期:1996-09-01 00:00:00

  • First-line endocrine treatment of breast cancer: aromatase inhibitor or antioestrogen?

    abstract::Until recently, endocrine therapy for breast cancer was relatively simple. If the tumour expressed hormone receptors, regardless of stage and age, tamoxifen was indicated. While this largely remains the case for premenopausal women, clinical trials in postmenopausal women have broadened our choice to include one of th...

    journal_title:British journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1038/sj.bjc.6601508

    authors: Wong ZW,Ellis MJ

    更新日期:2004-01-12 00:00:00

  • Is lack of surgery for older breast cancer patients in the UK explained by patient choice or poor health? A prospective cohort study.

    abstract:BACKGROUND:Older women have lower breast cancer surgery rates than younger women. UK policy states that differences in cancer treatment by age can only be justified by patient choice or poor health. METHODS:We investigate whether lack of surgery for older patients is explained by patient choice/poor health in a prospe...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2013.734

    authors: Lavelle K,Sowerbutts AM,Bundred N,Pilling M,Degner L,Stockton C,Todd C

    更新日期:2014-02-04 00:00:00