DKC1 enhances angiogenesis by promoting HIF-1α transcription and facilitates metastasis in colorectal cancer.

Abstract:

BACKGROUND:Dyskeratosis congenita 1 (DKC1) is dysregulated in several cancers. However, the expression and function of DKC1 in colorectal cancer (CRC) is rarely reported. METHODS:Tissue microarrays (TAMs) including 411 cases of CRC tissues and corresponding paracancerous tissues were used to examine the DKC1 expression. The correlations between the DKC1 expression and clinicopathological or survival characters were further analysed. The functions and molecular mechanism of DKC1 in CRC were investigated through a series of in vitro and in vivo experiments. RESULTS:The result showed that DKC1 expression was increased in CRC tissues. Increased DKC1 expression was associated with high grade of TNM stage, additional lymph node metastasis, and poor prognosis of patients with CRC. Multivariate COX analysis indicated that DKC1 can act as an independent prognostic factor for patients with CRC. DKC1 also facilitated the CRC angiogenesis and metastasis by increasing HIF-1α and VEGF expression levels. Chromatin immunoprecipitation assay demonstrated that DKC1 facilitated HIF-1α expression by regulating HIF-1α promoter activity. CONCLUSION:DKC1 appears to regulate CRC angiogenesis and metastasis through directly activating HIF-1α transcription. DKC1 can serve as an accurate indicator in predicting the prognosis of patients with CRC and act as a potential therapeutic target for CRC.

journal_name

Br J Cancer

authors

Hou P,Shi P,Jiang T,Yin H,Chu S,Shi M,Bai J,Song J

doi

10.1038/s41416-019-0695-z

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

668-679

issue

5

eissn

0007-0920

issn

1532-1827

pii

10.1038/s41416-019-0695-z

journal_volume

122

pub_type

杂志文章
  • Vegetable, fruit and antioxidant nutrient consumption and subsequent risk of hepatocellular carcinoma: a prospective cohort study in Japan.

    abstract::In a population-based prospective study of 19,998 Japanese individuals, consumption of vegetables, green-yellow and green leafy vegetables was inversely associated with the risk of hepatocellular carcinoma (101 cases), with multivariable hazard ratios for the highest vs lowest tertile of 0.61 (95% confidence interval ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6604843

    authors: Kurahashi N,Inoue M,Iwasaki M,Tanaka Y,Mizokami M,Tsugane S,JPHC Study Group.

    更新日期:2009-01-13 00:00:00

  • Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder.

    abstract::Recepteur d'Origine Nantais (RON) is a distinct receptor tyrosine kinase in the c-met proto-oncogene family. We examined the mutational and expression patterns of RON in eight human uroepithelial cell lines. Biological effects of RON overexpression on cancer cells were investigated in vitro, and the prognostic signifi...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6602593

    authors: Cheng HL,Liu HS,Lin YJ,Chen HH,Hsu PY,Chang TY,Ho CL,Tzai TS,Chow NH

    更新日期:2005-05-23 00:00:00

  • Laminin activates the p185HER2 oncoprotein and mediates growth inhibition of breast carcinoma cells.

    abstract::The interaction between laminin and the oncoprotein encoded by the c-erbB-2 oncogene was studied in vitro and in vivo in human breast carcinomas. In vitro analysis of breast carcinoma cell lines overexpressing p185HER2 revealed that laminin, but not fibronectin, induced tyrosine phosphorylation and down-modulation of ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1996.560

    authors: Tagliabue E,Ardini E,Pellegrini R,Campiglio M,Bufalino R,Jeschke M,Groner B,Colnaghi MI,Ménard S

    更新日期:1996-11-01 00:00:00

  • Quality of life after prostate cancer treatments in patients comparable at baseline.

    abstract:BACKGROUND:Previous studies on the effects of different prostate cancer treatments on quality of life, were confounded because patients were not comparable. This study examined treatment effects in more comparable groups. METHODS:From 2008-2011, 240 patients with localised prostate cancer were selected to be eligible ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2013.181

    authors: van Tol-Geerdink JJ,Leer JW,van Oort IM,van Lin EJ,Weijerman PC,Vergunst H,Witjes JA,Stalmeier PF

    更新日期:2013-05-14 00:00:00

  • Interaction of human serum albumin with anticancer agents in vitro.

    abstract::The influence of human serum albumin (HA) on the biological effects of 13 chemotherapeutic agents was studied in vitro in the human leukaemia cell line MOLT-3. On the basis of changes in biological activity influenced by HA, these drugs may be divided into three types. Type I agents include cis-diamminedichloroplatinu...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1980.103

    authors: Takahashi I,Ohnuma T,Kavy S,Bhardwaj S,Holland JF

    更新日期:1980-04-01 00:00:00

  • 3-aminobenzamide and/or O6-benzylguanine evaluated as an adjuvant to temozolomide or BCNU treatment in cell lines of variable mismatch repair status and O6-alkylguanine-DNA alkyltransferase activity.

    abstract::O6-benzylguanine (O6-BG) and 3-aminobenzamide (3-AB) inhibit the DNA repair proteins O6-alkylguanine-DNA alkyltransferase (AGT) and poly(ADP-ribose) polymerase (PARP) respectively. The effect of O6-BG and/or 3-AB on temozolomide and 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) cytotoxicity, was assessed in seven human tu...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1996.485

    authors: Wedge SR,Porteous JK,Newlands ES

    更新日期:1996-10-01 00:00:00

  • Second primary cancers of the breast: incidence and risk factors.

    abstract::Between 1946 and 1976 over 9,000 women with breast cancer were seen within one year of diagnosis at the A. Maxwell Evans Clinic (AMEC) in Vancouver, British Columbia. By 1978, 275 had a subsequent diagnosis of a second primary in the contralateral breast: 100 were diagnosed within 1 year, and 175 after 1 year of the f...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1984.12

    authors: Hislop TG,Elwood JM,Coldman AJ,Spinelli JJ,Worth AJ,Ellison LG

    更新日期:1984-01-01 00:00:00

  • Extreme assay sensitivity in molecular diagnostics further unveils intratumour heterogeneity in metastatic colorectal cancer as well as artifactual low-frequency mutations in the KRAS gene.

    abstract:BACKGROUND:Gene mutations in the RAS family rule out metastatic colorectal carcinomas (mCRCs) from anti-EGFR therapies. METHODS:We report a retrospective analysis by Sequenom Massarray and fast COLD-PCR followed by Sanger sequencing on 240 mCRCs. RESULTS:By Sequenom, KRAS and NRAS exons 2-3-4 were mutated in 52.9% (1...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2017.170

    authors: Mariani S,Bertero L,Osella-Abate S,Di Bello C,Francia di Celle P,Coppola V,Sapino A,Cassoni P,Marchiò C

    更新日期:2017-07-25 00:00:00

  • Cytology vs molecular analysis for the detection of head and neck squamous cell carcinoma in oesopharyngeal brush samples: a prospective study in 56 patients.

    abstract::Oesopharyngeal brush (OPB) sampling with cytological analysis can yield exfoliated cells from asymptomatic tumours of the upper aero-digestive tract and the oesophagus. In this study, we compared cytological evaluation and molecular analysis for the detection of exfoliated cancer cells sampled with an OPB. A total of ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6600953

    authors: Temam S,Trassard M,Leroux G,Bosq J,Luboinski B,Lenoir G,Bénard J,Janot F

    更新日期:2003-06-02 00:00:00

  • The incidence of cancers among second-generation Irish living in England and Wales.

    abstract::The incidence of ovarian, cervical, lung and prostatic cancer was higher in second-generation Irish living in England and Wales than in all other persons in England and Wales. A higher incidence of ovarian cancer was not found in first-generation Irish. Differences in socioeconomic status did not explain these pattern...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1998.608

    authors: Harding S

    更新日期:1998-10-01 00:00:00

  • Cisplatin, 5-fluorouracil and interferon alpha 2b for recurrent or metastatic head and neck cancer.

    abstract::On the basis of preclinical data suggesting the possibility of maximising the efficacy of 5-fluorouracil and cisplatin by interferon, a pilot clinical trial was initiated in recurrent and/or metastatic head and neck cancer. Thirty-four patients were treated with cisplatin at 100 mg m-2, followed by 5-fluorouracil at 1...

    journal_title:British journal of cancer

    pub_type: 临床试验,杂志文章

    doi:10.1038/bjc.1994.72

    authors: Cascinu S,Fedeli A,Luzi Fedeli S,Catalano G

    更新日期:1994-02-01 00:00:00

  • Quality of life in participants of a CRC screening program.

    abstract:BACKGROUND:Little is known about the effect of participating in a colorectal cancer (CRC) screening programme on quality of life (QOL), neither for participants with a negative nor for those with a positive test result. These findings, however, are important to evaluate the impact of CRC screening. METHODS:Participant...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2012.386

    authors: Kapidzic A,Korfage IJ,van Dam L,van Roon AH,Reijerink JC,Zauber AG,van Ballegooijen M,Kuipers EJ,van Leerdam ME

    更新日期:2012-10-09 00:00:00

  • Does thyroid-stimulating hormone influence the prognosis of patients with endometrial cancer? A multicentre trial.

    abstract:BACKGROUND:Thyroid function has been suggested to interfere with tumour biology and prognosis in different cancers. The present study was performed to investigate the impact of pre-therapeutic serum thyroid-stimulating hormone (TSH) levels on the prognosis of patients with endometrial cancer. METHODS:Pre-therapeutic s...

    journal_title:British journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1038/bjc.2013.282

    authors: Seebacher V,Hofstetter G,Polterauer S,Reinthaller A,Grimm C,Schwameis R,Taucher S,Wagener A,Marth C,Concin N

    更新日期:2013-07-09 00:00:00

  • GEIS-21: a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for the treatment of Ewing sarcoma of children and adults: a report from the Spanish sarcoma group (GEIS).

    abstract:BACKGROUND:First Spanish trial of Ewing sarcoma (ES) including adults and children with the aim to test the efficacy of Gemcitabine and Docetaxel (G/D) in newly diagnosed high-risk (HR) patients. METHODS:This was a prospective, multicentric, non-randomised, open study for patients ⩽40 years with newly diagnosed ES. HR...

    journal_title:British journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1038/bjc.2017.252

    authors: Mora J,Castañeda A,Perez-Jaume S,Lopez-Pousa A,Maradiegue E,Valverde C,Martin-Broto J,Garcia Del Muro X,Cruz O,Cruz J,Martinez-Trufero J,Maurel J,Vaz MA,de Alava E,de Torres C

    更新日期:2017-09-05 00:00:00

  • Cost-utility analysis of imatinib mesilate for the treatment of advanced stage chronic myeloid leukaemia.

    abstract::Imatinib mesilate (Glivec), Novartis Pharmaceuticals) is a novel therapy for the treatment of chronic myeloid leukaemia (CML). We evaluated the cost-effectiveness of imatinib (600 mg daily) when used for the treatment of patients in advanced stages of CML (accelerated phase and blast crisis) against conventional thera...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6601151

    authors: Gordois A,Scuffham P,Warren E,Ward S

    更新日期:2003-08-18 00:00:00

  • Dacarbazine (DTIC)-based chemotherapy or chemoimmunotherapy of patients with disseminated malignant melanoma.

    abstract::Combinations of dacarbazine (DTIC) and other cytotoxic agents or alpha-interferon were given to 136 patients in five different regimens. The total response rate was 32% (95% confidence interval 24-40%); 13% had a complete remission. Female patients had a significantly higher chance of response than male patients: 46% ...

    journal_title:British journal of cancer

    pub_type: 临床试验,杂志文章

    doi:10.1038/bjc.1994.372

    authors: Mulder NH,van der Graaf WT,Willemse PH,Koops HS,de Vries EG,Sleijfer DT

    更新日期:1994-10-01 00:00:00

  • Luminal membrane expression of mesothelin is a prominent poor prognostic factor for gastric cancer.

    abstract:BACKGROUND:Mesothelin is expressed in various types of malignant tumour, and we recently reported that expression of mesothelin was related to an unfavourable patient outcome in pancreatic ductal adenocarcinoma. In this study, we examined the clinicopathological significance of the mesothelin expression in gastric canc...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2012.235

    authors: Einama T,Homma S,Kamachi H,Kawamata F,Takahashi K,Takahashi N,Taniguchi M,Kamiyama T,Furukawa H,Matsuno Y,Tanaka S,Nishihara H,Taketomi A,Todo S

    更新日期:2012-06-26 00:00:00

  • Specific roles for the PI3K and the MEK-ERK pathway in IGF-1-stimulated chemotaxis, VEGF secretion and proliferation of multiple myeloma cells: study in the 5T33MM model.

    abstract::Insulin-like growth factor-1 (IGF-1) has been described as an important factor in proliferation, cell survival and migration of multiple myeloma (MM) cells. Angiogenesis correlates with development and prognosis of the MM disease. Vascular endothelial growth factor (VEGF) is one of the prominent factors involved in th...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6601613

    authors: Menu E,Kooijman R,Van Valckenborgh E,Asosingh K,Bakkus M,Van Camp B,Vanderkerken K

    更新日期:2004-03-08 00:00:00

  • A rodent model for testicular involvement in acute lymphoblastic leukaemia.

    abstract::The testis is the third common site of relapse after primary treatment of childhood acute lymphoblastic leukaemia, but in adults relatively few testicular relapses of acute lymphoblastic leukaemia have been reported. In the present investigation the differences in the behaviour of leukaemia in immature and mature rat ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1993.166

    authors: Jahnukainen K,Morris I,Roe S,Salmi TT,Mäkipernaa A,Pöllänen P

    更新日期:1993-05-01 00:00:00

  • A phase I/IIa study of adjuvant immunotherapy with tumour antigen-pulsed dendritic cells in patients with hepatocellular carcinoma.

    abstract:BACKGROUND:To date, no adjuvant treatment has been shown to have a clear benefit in patients with hepatocellular carcinoma (HCC). In this prospective phase I/IIa study, we evaluated the safety and efficacy of adjuvant dendritic cell (DC) therapy in HCC patients who received primary treatment for HCC. METHODS:Twelve HC...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2015.430

    authors: Lee JH,Lee Y,Lee M,Heo MK,Song JS,Kim KH,Lee H,Yi NJ,Lee KW,Suh KS,Bae YS,Kim YJ

    更新日期:2015-12-22 00:00:00

  • High prevalence of Clostridium difficile diarrhoea during intensive chemotherapy for disseminated germ cell cancer.

    abstract::A prospective, consecutive study of the aetiology of treatment-associated diarrhoea was conducted in 25 patients with disseminated germ cell cancer treated with intensive chemotherapy. Clostridium difficile was isolated in 45% of the diarrhoea episodes, which makes this species the most important bacterial pathogen in...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1992.334

    authors: Nielsen H,Daugaard G,Tvede M,Bruun B

    更新日期:1992-10-01 00:00:00

  • EpCAM (CD326) finding its role in cancer.

    abstract::Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of...

    journal_title:British journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1038/sj.bjc.6603494

    authors: Baeuerle PA,Gires O

    更新日期:2007-02-12 00:00:00

  • Increased expression of HGF and c-met in rat small intestine during recovery from methotrexate-induced mucositis.

    abstract::Chemotherapy or radiotherapy often cause mucosal damage in the gut (gut mucositis) in cancer patients. As a step to investigate mechanisms underlying subsequent intestinal repair, we have examined the expression profiles of hepatocyte growth factor (HGF) and its receptor c-met, two molecules previously implicated in t...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1054/bjoc.1999.1023

    authors: Xian CJ,Couper R,Howarth GS,Read LC,Kallincos NC

    更新日期:2000-02-01 00:00:00

  • Impact of non-axillary sentinel node biopsy on staging and treatment of breast cancer patients.

    abstract::The purpose of this study was to evaluate the occurrence of lymphatic drainage to non-axillary sentinel nodes and to determine the implications of this phenomenon. A total of 549 breast cancer patients underwent lymphoscintigraphy after intratumoural injection of (99m)Tc-nanocolloid. The sentinel node was intraoperati...

    journal_title:British journal of cancer

    pub_type: 临床试验,杂志文章

    doi:10.1038/sj.bjc.6600359

    authors: Tanis PJ,Nieweg OE,Valdés Olmos RA,Peterse JL,Rutgers EJ,Hoefnagel CA,Kroon BB

    更新日期:2002-09-23 00:00:00

  • Detection of occult carcinomatous diffusion in lymph nodes from head and neck squamous cell carcinoma using real-time RT-PCR detection of cytokeratin 19 mRNA.

    abstract::The aim of the present study was to evaluate the occult lymph node carcinomatous diffusion in head and neck squamous cell carcinoma (HNSCC). A total of 1328 lymph nodes from 31 patients treated between 2004 and 2005 were prospectively evaluated by routine haematoxylin-eosin-safran (HES) staining, immunohistochemistry ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6603073

    authors: Tao L,Lefèvre M,Ricci S,Saintigny P,Callard P,Périé S,Lacave R,Bernaudin JF,Lacau St Guily J

    更新日期:2006-04-24 00:00:00

  • Allele loss from large regions of chromosome 17 is common only in certain histological subtypes of ovarian carcinomas.

    abstract::Using a panel of ten polymorphic markers, we examined the frequency of loss of heterozygosity (LOH) on chromosome 17 in 55 sporadic ovarian tumours. LOH on 17p and 17q was observed to be 50% and 62% respectively. LOH at D17S5 was detected in 24/36 (67%) of malignant cases and in 19/43 (44%) at TP53; the marker D17S855...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1996.594

    authors: Papp J,Csokay B,Bosze P,Zalay Z,Toth J,Ponder B,Olah E

    更新日期:1996-11-01 00:00:00

  • Socioeconomic position, stage of lung cancer and time between referral and diagnosis in Denmark, 2001-2008.

    abstract:INTRODUCTION:We investigated the association between socioeconomic position, stage at diagnosis, and length of period between referral and diagnosis in a nationwide cohort of lung cancer patients. METHODS:Through the Danish Lung Cancer Register, we identified 18,103 persons diagnosed with lung cancer (small cell and n...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.2011.342

    authors: Dalton SO,Frederiksen BL,Jacobsen E,Steding-Jessen M,Østerlind K,Schüz J,Osler M,Johansen C

    更新日期:2011-09-27 00:00:00

  • Effect of glucose transport inhibitors on vincristine efflux in multidrug-resistant murine erythroleukaemia cells overexpressing the multidrug resistance-associated protein (MRP) and two glucose transport proteins, GLUT1 and GLUT3.

    abstract::The relationship between mammalian facilitative glucose transport proteins (GLUT) and multidrug resistance was examined in two vincristine (VCR)-selected murine erythroleukaemia (MEL) PC4 cell lines. GLUT proteins, GLUT1 and GLUT3, were constitutively coexpressed in the parental cell line and also in the VCR-selected ...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1997.27

    authors: Martell RL,Slapak CA,Levy SB

    更新日期:1997-01-01 00:00:00

  • Stimulation of the apoptotic response as a basis for the therapeutic synergism of lonidamine and cisplatin in combination in human tumour xenografts.

    abstract::The pharmacological interest in lonidamine is related to its ability to enhance the cytotoxic effects of several DNA-damaging anti-tumour agents. This study was undertaken to better understand the in vivo interaction between lonidamine and cisplatin in the treatment of human tumour xenografts, including three carcinom...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/bjc.1998.69

    authors: De Cesare M,Pratesi G,Giusti A,Polizzi D,Zunino F

    更新日期:1998-01-01 00:00:00

  • Prognostic significance of circumferential resection margin involvement following oesophagectomy for cancer.

    abstract::The factors affecting long-term survival following oesophagectomy for oesophageal cancer are poorly understood. We examined the significance of microscopic tumour involvement at the circumferential resection margin (CRM) on postoperative survival following oesophagectomy. The case notes of 329 patients who underwent a...

    journal_title:British journal of cancer

    pub_type: 杂志文章

    doi:10.1038/sj.bjc.6600931

    authors: Khan OA,Fitzgerald JJ,Soomro I,Beggs FD,Morgan WE,Duffy JP

    更新日期:2003-05-19 00:00:00