Resistance to the mTOR-inhibitor RAD001 elevates integrin α2- and β1-triggered motility, migration and invasion of prostate cancer cells.

Abstract:

BACKGROUND:Inhibitors of the mammalian target of rapamycin (mTOR) might become a novel tool to treat advanced prostate cancer. However, chronic drug exposure may trigger resistance, limiting the utility of mTOR inhibitors. METHODS:Metastatic potential of PC3 prostate cancer cells, susceptible (PC3(par)) or resistant (PC3(res)) to the mTOR-inhibitor RAD001 was investigated. Adhesion to vascular endothelium or immobilised collagen, fibronectin and laminin was quantified. Motility, migration and invasion were explored by modified Boyden chamber assay. Integrin α and β subtypes were analysed by flow cytometry, western blotting and real-time PCR. Integrin-related signalling, EGFr, Akt, p70S6kinase and ERK1/2 activation were determined. RESULTS:Adhesion was reduced, whereas motility, migration and invasion were enhanced in PC3(res). The α2 and β1 integrin subtypes were dramatically elevated, integrins α1 and α6 were lowered, whereas α5 was nearly lost in PC3(res). Activation of the Akt signalling pathway was strongly upregulated in these cells. Treating PC3(par) cells with RAD001 reduced motility, migration and invasion and deactivated Akt signalling. Blocking studies revealed that α2 and β1 integrins significantly trigger the motile behaviour of the tumour cells. CONCLUSION:Chronic RAD001 treatment caused resistance development characterised by distinct modification of the integrin-expression profile, driving prostate cancer cells towards high motility.

journal_name

Br J Cancer

authors

Tsaur I,Makarević J,Juengel E,Gasser M,Waaga-Gasser AM,Kurosch M,Reiter M,Wedel S,Bartsch G,Haferkamp A,Wiesner C,Blaheta RA

doi

10.1038/bjc.2012.313

subject

Has Abstract

pub_date

2012-08-21 00:00:00

pages

847-55

issue

5

eissn

0007-0920

issn

1532-1827

pii

bjc2012313

journal_volume

107

pub_type

杂志文章
  • MicroRNA in lung cancer.

    abstract::MicroRNAs (miRNAs) are small non-protein-coding RNAs that function as endogenous negative gene regulators. Dysfunctions of miRNAs are frequently found in malignancies, including lung cancer. In this review, we summarise the current understanding of miRNAs in lung cancer tumourigenesis, and highlight their potential in...

    journal_title:British journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1038/sj.bjc.6605901

    authors: Lin PY,Yu SL,Yang PC

    更新日期:2010-10-12 00:00:00

  • A phase III placebo-controlled study in advanced head and neck cancer using intratumoural cisplatin/epinephrine gel.

    abstract::Patients with recurrent or refractory head and neck squamous cell carcinoma received cisplatin/epinephrine injectable gel or placebo gel injected directly into the clinically dominant tumour. The double-blind phase III trial comprised of up to 6 weekly treatments over 8 weeks, 4 weekly evaluation visits, and then mont...

    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.6600588

    authors: Werner JA,Kehrl W,Pluzanska A,Arndt O,Lavery KM,Glaholm J,Dietz A,Dyckhoff G,Maune S,Stewart ME,Orenberg EK,Leavitt RD

    更新日期:2002-10-21 00:00:00

  • Hormone replacement therapy, body mass, and the risk of colorectal cancer among postmenopausal women from Germany.

    abstract::Previous studies have reported inconsistent results regarding the modifying effect of hormone replacement therapy (HRT) on the association of body mass index (BMI) and the risk of colorectal cancer (CRC) among postmenopausal women. We assessed the use of HRT and BMI in 208 postmenopausal women with histologically conf...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6604066

    authors: Hoffmeister M,Raum E,Winter J,Chang-Claude J,Brenner H

    更新日期:2007-12-03 00:00:00

  • Increased level of exhaled nitric oxide and up-regulation of inducible nitric oxide synthase in patients with primary lung cancer.

    abstract::Monocyte-macrophage series have an important role in host surveillance against cancer. The cytotoxic/cytostatic activity of macrophages is, to a great extent, attributed to the up-regulation of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO). Here, in 28 patients with primary lung cancer and...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1998.528

    authors: Liu CY,Wang CH,Chen TC,Lin HC,Yu CT,Kuo HP

    更新日期:1998-08-01 00:00:00

  • Educational attainment among survivors of childhood cancer: a population-based cohort study in Denmark.

    abstract::We identified 2384 patients in the Danish Cancer Register in whom cancer had been diagnosed in 1960-1996 before they reached the age of 20 and compared them with 53 143 sex- and age-matched controls identified from the Register of Population Statistics. Complete education records and demographic and socioeconomic info...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6602085

    authors: Koch SV,Kejs AM,Engholm G,Johansen C,Schmiegelow K

    更新日期:2004-08-31 00:00:00

  • Hepatic arterial floxuridine as second-line treatment for systemic fluorouracil-resistant colorectal liver metastases.

    abstract::Hepatic arterial floxuridine (HAI) in 35 patients with systemic fluorouracil/folinic acid-resistant colorectal liver metastases achieved a 14% partial response and 26% disease stabilization rate, with a median response duration of 7 months from onset of HAI. ...

    journal_title:British journal of cancer

    pub_type: 临床试验,杂志文章

    doi:10.1038/bjc.1998.627

    authors: Fordy C,Glover C,Davies MM,Allen-Mersh TG

    更新日期:1998-10-01 00:00:00

  • Cell cycle phase influences tumour cell sensitivity to aminolaevulinic acid-induced photodynamic therapy in vitro.

    abstract::Photodynamic therapy (PDT) is a form of cancer treatment based on the destruction of cells by the interaction of light, oxygen and a photosensitizer. Aminolaevulinic acid (ALA) is the prodrug of the photosensitizer protoporphyrin IX (PpIX). ALA-induced PDT depends on the rate of cellular synthesis of PpIX, which may v...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1998.441

    authors: Wyld L,Smith O,Lawry J,Reed MW,Brown NJ

    更新日期:1998-07-01 00:00:00

  • Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas.

    abstract::In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish t...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1994.207

    authors: Patterson H,Gill S,Fisher C,Law MG,Jayatilake H,Fletcher CD,Thomas M,Grimer R,Gusterson BA,Cooper CS

    更新日期:1994-06-01 00:00:00

  • Evaluation of p16INK4a expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation.

    abstract:BACKGROUND:A remarkably better prognosis is associated with oropharyngeal squamous cell carcinomas (OPSCC) driven by human papillomaviruses (HPV) compared with HPV-negative OPSCC. Consequently, de-escalation of standard treatment has been suggested. Due to modest specificity rates, debates are ongoing, whether p16INK4a...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/s41416-020-0964-x

    authors: Wagner S,Prigge ES,Wuerdemann N,Reder H,Bushnak A,Sharma SJ,Obermueller T,von Knebel Doeberitz M,Dreyer T,Gattenlöhner S,Wolf G,Pons-Kühnemann J,Wittekindt C,Klussmann JP

    更新日期:2020-09-01 00:00:00

  • Photodynamic therapy using intravenous delta-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats.

    abstract::The efficacy of photodynamic therapy (PDT) using delta-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) sensitisation and laser light at 635 nm was investigated in the treatment of experimental hepatic tumours. The model of liver tumours was induced either by local inoculation or by administration of tumour...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1996.584

    authors: Svanberg K,Liu DL,Wang I,Andersson-Engels S,Stenram U,Svanberg S

    更新日期:1996-11-01 00:00:00

  • Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis.

    abstract::Metastasis of colorectal carcinomas rarely occurs in cirrhotic livers. Our study investigated the influence of activated Kupffer cells from cirrhotic rat livers on hepatic colonization and FasR-mediated apoptosis of colon cancer cells. A rat colon cancer cell line, RCN-9, was used to inoculate rat livers. Treatment wi...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1054/bjoc.2000.1737

    authors: Song E,Chen J,Ouyang N,Wang M,Exton MS,Heemann U

    更新日期:2001-05-04 00:00:00

  • N-methylformamide induces changes on adhesive properties and lung-colonizing potential of M14 melanoma cells.

    abstract::We have studied whether N-methylformamide can affect the expression pattern of adhesion molecules and the attachment behaviour of M14 human melanoma cells. The role of N-methylformamide on experimental and spontaneous pulmonary metastases from M14 cells in nude mice was also investigated. We demonstrate that N-methylf...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1998.35

    authors: Del Bufalo D,Leonetti C,Bucci B,Amedeo C,Falcioni R,Biroccio A,Zupi G

    更新日期:1998-01-01 00:00:00

  • Anti-tumour cytotoxin produced by human monocytes: studies on its mode of action.

    abstract::Human monocytes can be induced to synthesize a cytotoxin which affects certain tumour cell lines. The interaction of monocyte cytotoxin with a susceptible cell line (L929) has been studied to obtain clues to the mode of action of the cytotoxin. The cytotoxin acts directly on the cells rather than on the culture medium...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1983.205

    authors: Matthews N

    更新日期:1983-09-01 00:00:00

  • A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer.

    abstract::The aim of this phase I study was to determine the maximum tolerated dose of a 3-h infusion of paclitaxel, combined with carboplatin at a fixed AUC of 7 mg ml-1 min every 4 weeks for up to six cycles and to evaluate any possible pharmacokinetic interaction. Twelve chemonaive patients with ovarian cancer were treated w...

    journal_title:British journal of cancer

    pub_type: 临床试验,杂志文章

    doi:10.1038/bjc.1997.47

    authors: Siddiqui N,Boddy AV,Thomas HD,Bailey NP,Robson L,Lind MJ,Calvert AH

    更新日期:1997-01-01 00:00:00

  • Early diagnosis of oesophageal cancer.

    abstract::Squamous cell carcinoma and adenocarcinoma of the oesophagus are cancers that develop from distinct epithelial sub-types; however, they are both related to chronic inflammation of differing aetiologies. Inflammation leads to somatically inherited genetic mutations altering control of the cell cycle, DNA replication an...

    journal_title:British journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1038/sj.bjc.6605126

    authors: Bird-Lieberman EL,Fitzgerald RC

    更新日期:2009-07-07 00:00:00

  • Carboplatin plus paclitaxel in extensive small cell lung cancer: a multicentre phase 2 study.

    abstract::A multicentre phase 2 trial (single-stage design) was undertaken to test the efficacy and toxicity of carboplatin (AUC 6 according to Calvert) plus paclitaxel (175 mg/m(2)3-h infusion) every 4 weeks in the first line treatment of patients affected by extensive small cell lung cancer. The primary end-point of the trial...

    journal_title:British journal of cancer

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1054/bjoc.2000.1541

    authors: Gridelli C,Manzione L,Perrone F,Veltri E,Cioffi R,Caprio MG,Frontini L,Rossi A,Barletta E,Barzelloni ML,Bilancia D,Gallo C

    更新日期:2001-01-05 00:00:00

  • Characterization of human sarcoma antigen S3.

    abstract::An antigen common to human sarcomas, S3, has been further characterized. It is antigenically distinct from human blood-group substances A and B and from heterophile antigens such as Forssman, infectious mononucleosis and serum sickness antigens. Whilst S3 antigen preparations may contain small amounts of CEA and AFP t...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1981.43

    authors: Sethi JK,Hirshaut Y

    更新日期:1981-03-01 00:00:00

  • Serine protease-induced enhancement of blood-borne metastasis of rat ascites tumour cells and its prevention with deoxyribonuclease.

    abstract::Serine proteases, such as alpha-chymotrypsin or elastase, caused an aggregation of rat ascites tumour cell lines, AH-130, AH-109A and YS, in a protein free medium which preserved the cell viability. This aggregation, which was monitored spectrophotometrically, was dependent upon the protease activities and was resista...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1990.339

    authors: Sugihara S,Yamamoto T,Tsuruta J,Tanaka J,Kambara T,Hiraoka T,Miyauchi Y

    更新日期:1990-10-01 00:00:00

  • Risk of cancer in patients with dermatomyositis or polymyositis, and follow-up implications: a Scottish population-based cohort study.

    abstract::We conducted a national, retrospective population-based cohort study of 705 patients hospitalized with a first diagnosis of dermatomyositis (DM) or polymyositis (PM) during 1982-1996 based on linkage of hospital discharge, cancer registration, and death records in Scotland. Risks of cancer were assessed by calculating...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1054/bjoc.2001.1699

    authors: Stockton D,Doherty VR,Brewster DH

    更新日期:2001-07-06 00:00:00

  • Potentiation of temozolomide-induced cytotoxicity: a comparative study of the biological effects of poly(ADP-ribose) polymerase inhibitors.

    abstract::Four poly(ADP-ribose) polymerase (PADPRP) inhibitors [3-aminobenzamide, benzamide, 3,4-dihydro-5-methoxyisoquinolin-1(2H)-one (PD 128763) and 8-hydroxy-2-methylquinazolin-4(3H)-one (NU1025)] were compared with respect to their effects on a number of biological end points. The following parameters were assessed: their ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1995.423

    authors: Boulton S,Pemberton LC,Porteous JK,Curtin NJ,Griffin RJ,Golding BT,Durkacz BW

    更新日期:1995-10-01 00:00:00

  • A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumours.

    abstract:BACKGROUND:Veliparib is a potent poly(ADP-ribose) polymerase inhibitor. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib combined with various FOLFIRI regimens in patients with solid tumours. METHODS:Patients received veliparib (10-270 mg BID, days...

    journal_title:British journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1038/s41416-018-0003-3

    authors: Berlin J,Ramanathan RK,Strickler JH,Subramaniam DS,Marshall J,Kang YK,Hetman R,Dudley MW,Zeng J,Nickner C,Xiong H,Komarnitsky P,Shepherd SP,Hurwitz H,Lenz HJ

    更新日期:2018-04-01 00:00:00

  • Continued inadequacies in data sources for the evaluation of cancer services.

    abstract::There is a need to evaluate cancer services and provide a baseline on current treatment success and organization. This study shows that this process may be severely hindered by case note destruction or inaccessibility and incomplete information. This is an ongoing problem that needs to be addressed now. ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1997.21

    authors: Smith SJ,Muir KR,Wolstenholme JL,Thornhill KG,Zamorski A,Tolley K,Logan RF,Chilvers CE

    更新日期:1997-01-01 00:00:00

  • How should cancer presenting as a malignant pleural effusion be managed?

    abstract::The objective of the study was to review the natural history of patients with a malignant pleural effusion but without obvious evidence of a primary, to assess the value of investigations used to look for a primary and to assess the response to palliative chemotherapy. This was done by a retrospective study of patient...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1996.444

    authors: Bonnefoi H,Smith IE

    更新日期:1996-09-01 00:00:00

  • Familial breast cancer: a controlled study of risk perception, psychological morbidity and health beliefs in women attending for genetic counselling.

    abstract::The present study set out to evaluate perceptions of risk, psychological morbidity and health behaviours in women with a family history of breast cancer who have attended genetic counselling and determine how these differ from general population risk women. Data were collected from 62 genetic counselees (cases) attend...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1996.387

    authors: Lloyd S,Watson M,Waites B,Meyer L,Eeles R,Ebbs S,Tylee A

    更新日期:1996-08-01 00:00:00

  • [18F]FDG and [18F]FLT uptake in human breast cancer cells in relation to the effects of chemotherapy: an in vitro study.

    abstract::Increased 2'-deoxy-2'-[18F]fluoro-D-glucose (FDG) uptake is the most commonly used marker for positron emission tomography in oncology. However, a proliferation tracer such as 3'-deoxy-3'-[18F]fluorothymidine (FLT) might be more specific for cancer. 3'-deoxy-3'-[18F]fluorothymidine uptake is dependent on thymidine kin...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6604523

    authors: Direcks WG,Berndsen SC,Proost N,Peters GJ,Balzarini J,Spreeuwenberg MD,Lammertsma AA,Molthoff CF

    更新日期:2008-08-05 00:00:00

  • The 1987 Walter Hubert lecture. Regulation and deficiencies in DNA repair.

    abstract::A number of rare human inherited syndromes are associated with apparent defects in DNA repair and a greatly increased frequency of cancer. Cell lines derived from such individuals phenotypically resemble certain bacterial mutant strains that have increased sensitivity to radiation or chemical agents and well character...

    journal_title:British journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1038/bjc.1987.163

    authors: Lindahl T

    更新日期:1987-08-01 00:00:00

  • Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues.

    abstract::Extracellular proteases of the matrix metalloproteinase (MMP) and serine protease families participate in many aspects of tumour growth and metastasis. Using quantitative real-time RT-PCR analysis, we have undertaken a comprehensive survey of the expression of these enzymes and of their natural inhibitors in 44 cases ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6602630

    authors: Riddick AC,Shukla CJ,Pennington CJ,Bass R,Nuttall RK,Hogan A,Sethia KK,Ellis V,Collins AT,Maitland NJ,Ball RY,Edwards DR

    更新日期:2005-06-20 00:00:00

  • Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer.

    abstract:BACKGROUND:Anti-EGFR antibody, cetuximab, improves overall survival (OS) in K-ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor receptor ligand epiregulin (EREG) gene expression may further predict cetuximab benefit. METHODS:Tumour samples from a phase III clinical trial of cetuximab plu...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2013.753

    authors: Jonker DJ,Karapetis CS,Harbison C,O'Callaghan CJ,Tu D,Simes RJ,Malone DP,Langer C,Tebbutt N,Price TJ,Shapiro J,Siu LL,Wong RP,Bjarnason G,Moore MJ,Zalcberg JR,Khambata-Ford S

    更新日期:2014-02-04 00:00:00

  • Genetic and epigenetic analyses of MBD3 in colon and lung cancer.

    abstract::MBD3: is a member of the methyl-CpG-binding domain family and is located on chromosome 19p13.3, a region of loss of heterozygosity in colon and lung cancers. We therefore screened samples for abnormalities in MBD3. Our results indicate that MBD3 is not a major target of genetic and epigenetic alteration in these cance...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6601776

    authors: Zhu Y,Harrison DJ,Bader SA

    更新日期:2004-05-17 00:00:00

  • Childhood rhabdomyosarcoma: experience of the Children's Solid Tumour Group.

    abstract::Seventy three children with rhabdomyosarcoma were treated by members of the Children's Solid Tumour Group during the period, 1974-1981. The extent of disease at diagnosis was found to be the major influence affecting outcome. Children with tumours confined to the tissue of origin with no evidence of nodal or metastati...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1983.175

    authors: Kingston JE,McElwain TJ,Malpas JS

    更新日期:1983-08-01 00:00:00