当前位置： SCI文献检索 > ONCOGENE期刊下所有文献 > Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1α mediated by the PTEN/PI3K/Akt pathway.

Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1α mediated by the PTEN/PI3K/Akt pathway.

Abstract：

:Mel-18 has been implicated in several processes in tumor progression, in which the Akt pathway is involved as an important key molecular event. However, the function of Mel-18 in human cancers has not been fully established yet. Here, we examined the effect of Mel-18 on tumor angiogenesis in human breast cancer, and found that Mel-18 was a novel regulator of HIF-1α. Mel-18 negatively regulated the HIF-1α expression and its target gene VEGF transcription during both normoxia and hypoxia. We demonstrated that Mel-18 regulated the HIF-1α expression and activity via the PI3K/Akt pathway. Loss of Mel-18 downregulated Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression, consequently activating the PI3K/Akt/MDM2 pathway, and leading to an increase of HIF-1α protein level. Mel-18 modulated the HIF-1α transcriptional activity via regulating the cytoplasmic retention of FOXO3a, a downstream effector of Akt, and recruitment of HIF-1α/CBP complex to the VEGF promoter. Furthermore, our data shows that Mel-18 blocked tumor angiogenesis both in vitro and in vivo. Mel-18 overexpression inhibited in vitro tube formation in human umbilical endothelial cells (HUVECs). Xenografts in NOD/SCID mice derived from stably Mel-18 knocked down MCF7 human breast cancer cells showed increased tumor volume, microvessel density, and phospho-Akt and HIF-1α expression levels. In conclusion, our findings provide that Mel-18 is a novel regulator of tumor angiogenesis through regulating HIF-1α and its target VEGF expressions mediated by the PTEN/PI3K/Akt pathway, suggesting a new tumor-suppressive role of Mel-18 in human breast cancer.

journal_name

Oncogene

journal_title

Oncogene

authors

Park JH,Lee JY,Shin DH,Jang KS,Kim HJ,Kong G

doi

10.1038/onc.2011.174

subject

Has Abstract

pub_date

2011-11-10 00:00:00

pages

4578-89

issue

45

eissn

0950-9232

issn

1476-5594

pii

onc2011174

journal_volume

30

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • v-Myb represses the transcription of Ets-2.

    abstract：:The v-Myb oncogene causes monoblastic leukemia and transforms only myelomonocytic cells in culture. The v-Myb protein is nuclear and binds to specific DNA sequences. To identify genes regulated by v-Myb, we utilized primary cells transformed by a retrovirus encoding a v-Myb-estrogen receptor (ER) fusion protein. The E...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1209868

    authors： Wang DM,Sevcikova S,Wen H,Roberts S,Lipsick JS

    更新日期：2007-02-22 00:00:00

  • Ecotropic viral integration site 1, a novel oncogene in prostate cancer.

    abstract：:Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer in men in the western world. Mutations in tumor suppressor genes and in oncogenes are important for PCa progression, whereas the role of stem cell proteins in prostate carcinogenesis is insufficiently examined. This study investigates the role o...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2016.325

    authors： Queisser A,Hagedorn S,Wang H,Schaefer T,Konantz M,Alavi S,Deng M,Vogel W,von Mässenhausen A,Kristiansen G,Duensing S,Kirfel J,Lengerke C,Perner S

    更新日期：2017-03-01 00:00:00

  • TGFβ signaling in head and neck squamous cell carcinoma.

    abstract：:Transforming growth factor beta (TGFβ) is a key regulator of epithelial cell proliferation, immune function and angiogenesis. Because TGFβ signaling maintains epithelial homeostasis, dysregulated TGFβ signaling is common in many malignancies, including head and neck squamous cell carcinoma (HNSCC). Defective TGFβ sign...

    journal_title：Oncogene

    pub_type： 杂志文章,评审

    doi：10.1038/onc.2010.306

    authors： White RA,Malkoski SP,Wang XJ

    更新日期：2010-10-07 00:00:00

  • Bioengineered tumor microenvironments with naked mole rats high-molecular-weight hyaluronan induces apoptosis in breast cancer cells.

    abstract：:The naked mole rat (nmr) is cancer resistant due to the abundant production of extremely high-molecular-weight hyaluronan (EHMW-HA). However, whether EHMW-HA has similar anti-cancer effects in mice and humans remains to be determined. The present study used breast cancer cells to clarify the effect of EHMW-HA on breas...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/s41388-019-0719-4

    authors： Zhao Y,Qiao S,Hou X,Tian H,Deng S,Ye K,Nie Y,Chen X,Yan H,Tian W

    更新日期：2019-05-01 00:00:00

  • Developmental regulation of intermediate filament and actin mRNAs during myogenesis is disrupted by oncogenic ras genes.

    abstract：:Terminal differentiation of skeletal myoblasts is accompanied by down-regulation of vimentin and beta-, gamma-actins and up-regulation of desmin and sarcomeric alpha-actin(s). To investigate whether the normal decline in expression of vimentin and beta-, gamma-actins was coupled to withdrawal of proliferating myoblast...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Olson EN,Capetanaki YG

    更新日期：1989-07-01 00:00:00

  • The p53 knowledgebase: an integrated information resource for p53 research.

    abstract：:The p53 tumor suppressor protein plays a central role in maintaining genomic integrity by occupying a nodal point in the DNA damage control pathway. Here it integrates a wide variety of signals, responding in one of several ways, that is, cell cycle arrest, senescence or programmed cell death (apoptosis). Mutations in...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1209952

    authors： Lim YP,Lim TT,Chan YL,Song AC,Yeo BH,Vojtesek B,Coomber D,Rajagopal G,Lane D

    更新日期：2007-03-08 00:00:00

  • Tumor formation in mice with somatic inactivation of the retinoblastoma gene in interphotoreceptor retinol binding protein-expressing cells.

    abstract：:The retinoblastoma suppressor gene product Rb has been assigned a critical role in cell cycle regulation, the induction of differentiation, and inhibition of oncogenic transformation. Inheritance of a mutant RB allele in humans is responsible for bilateral retinoblastoma, a malignant tumor of the retina. Trilateral re...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1205575

    authors： Vooijs M,te Riele H,van der Valk M,Berns A

    更新日期：2002-07-11 00:00:00

  • Cleavage of Mcl-1 by caspases impaired its ability to counteract Bim-induced apoptosis.

    abstract：:Mcl-1 is an antiapoptotic member of the Bcl-2 family that can promote cell viability. We report here that Mcl-1 is a new substrate for caspases during induction of apoptosis. Mcl-1 cleavage occurs after Asp127 and Asp157 and generates four fragments of 24, 19, 17 and 12 kDa in both intact cells and in vitro, an effect...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1208069

    authors： Herrant M,Jacquel A,Marchetti S,Belhacène N,Colosetti P,Luciano F,Auberger P

    更新日期：2004-10-14 00:00:00

  • Inhibition of androgen receptor activity by histone deacetylase 4 through receptor SUMOylation.

    abstract：:The transcriptional activity of the androgen receptor (AR) is regulated by both ligand binding and post-translational modifications, including acetylation and small ubiquitin-like modifier (SUMO)ylation. Histone deacetylases (HDACs) are known to catalyze the removal of acetyl groups from both histones and non-histone ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2010.600

    authors： Yang Y,Tse AK,Li P,Ma Q,Xiang S,Nicosia SV,Seto E,Zhang X,Bai W

    更新日期：2011-05-12 00:00:00

  • The induction and activation of STAT1 by all-trans-retinoic acid are mediated by RAR beta signaling pathways in breast cancer cells.

    abstract：:Retinoic acid receptor-beta (RAR beta) and signal transducer and activator of transcription 1 (STAT1) are important mediators of the antiproliferative and apoptotic actions of retinoids and cytokines/growth factors, respectively. Expression of both RAR beta and STAT1 is lost in most breast cancer cell lines but it can...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1203084

    authors： Shang Y,Baumrucker CR,Green MH

    更新日期：1999-11-18 00:00:00

  • The three transforming regions of SV40 T antigen are required for immortalization of primary mouse embryo fibroblasts.

    abstract：:Simian virus 40 (SV40) is a small DNA tumor virus whose early region gene product, large T antigen, is sufficient to immortalize primary rodent cells and transform established rodent cell lines. Three functional domains of large T antigen are required for transformation of the rat embryo fibroblast REF 52 cell line: t...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Conzen SD,Cole CN

    更新日期：1995-12-07 00:00:00

  • Disruption of the antiproliferative TGF-beta signaling pathways in human pancreatic cancer cells.

    abstract：:Resistance to TGF-beta1 occurred in pancreatic cancer cells suggesting that inactivation of TGF-beta inhibitory signaling pathways may play an important role in human pancreatic cancer. The aim of our study was to determine the presence of alterations in the main putative components of the TGF-beta inhibitory signalin...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1202118

    authors： Villanueva A,García C,Paules AB,Vicente M,Megías M,Reyes G,de Villalonga P,Agell N,Lluís F,Bachs O,Capellá G

    更新日期：1998-10-15 00:00:00

  • Integrative functional genomic analysis identifies epigenetically regulated fibromodulin as an essential gene for glioma cell migration.

    abstract：:An integrative functional genomics study of multiple forms of data are vital for discovering molecular drivers of cancer development and progression. Here, we present an integrated genomic strategy utilizing DNA methylation and transcriptome profile data to discover epigenetically regulated genes implicated in cancer ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2016.176

    authors： Mondal B,Patil V,Shwetha SD,Sravani K,Hegde AS,Arivazhagan A,Santosh V,Kanduri M,Somasundaram K

    更新日期：2017-01-05 00:00:00

  • Identification of RASSF8 as a candidate lung tumor suppressor gene.

    abstract：:The RASSF8 gene, which maps close to the KRAS2 gene, contains a RAS-associated domain and encodes a protein that is evolutionarily conserved from fish to humans. Analysis of the RASSF8 transcript revealed a complex expression pattern of 5'-UTR mRNA isoforms in normal lung and in lung adenocarcinomas (ADCAs), with no a...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1209422

    authors： Falvella FS,Manenti G,Spinola M,Pignatiello C,Conti B,Pastorino U,Dragani TA

    更新日期：2006-06-29 00:00:00

  • Prolactin induces c-Myc expression and cell survival through activation of Src/Akt pathway in lymphoid cells.

    abstract：:Stimulation of resting W53 cells (lymphoid murine cells expressing prolactin (PRL) receptor) by PRL induced expression of growth-related immediate-early genes (IEG), and proliferation through activation of the Src kinases. Since IEG are essential for cell cycle progression, we have studied how PRL controls expression ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1208002

    authors： Domínguez-Cáceres MA,García-Martínez JM,Calcabrini A,González L,Porque PG,León J,Martín-Pérez J

    更新日期：2004-09-23 00:00:00

  • Induction of the IL-13 receptor alpha2-chain by IL-4 and IL-13 in human keratinocytes: involvement of STAT6, ERK and p38 MAPK pathways.

    abstract：:IL-4 and IL-13 are related cytokines which induce both pro- and anti-inflammatory effects depending on the cell type they act upon and the nature of the receptors expressed. The type I receptor complex is composed of the IL-4Ralpha and gammac and only binds IL-4, whereas, in the type II receptor, IL-4Ralpha dimerizes ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1204629

    authors： David M,Ford D,Bertoglio J,Maizel AL,Pierre J

    更新日期：2001-10-11 00:00:00

  • NF-kappaB signaling, liver disease and hepatoprotective agents.

    abstract：:The NF-kappaB signaling pathway has particular relevance to several liver diseases including hepatitis (liver infection by Helicobacter, viral hepatitis induced by HBV and HCV), liver fibrosis and cirrhosis and hepatocellular carcinoma. Furthermore, the NF-kappaB signaling pathway is a potential target for development...

    journal_title：Oncogene

    pub_type： 杂志文章,评审

    doi：10.1038/onc.2008.300

    authors： Sun B,Karin M

    更新日期：2008-10-20 00:00:00

  • Skp2-mediated ubiquitination and mitochondrial localization of Akt drive tumor growth and chemoresistance to cisplatin.

    abstract：:The E3 ligase S-phase kinase-associated protein 2(Skp2) is overexpressed in human cancers and correlated with poor prognosis, but its contributions to tumorigenesis and chemoresistance in nasopharyngeal carcinoma (NPC) are not evident. Herein we show that Skp2 is highly expressed in NPC tumor tissues and cell lines. K...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/s41388-019-0955-7

    authors： Yu X,Wang R,Zhang Y,Zhou L,Wang W,Liu H,Li W

    更新日期：2019-12-01 00:00:00

  • Activation of the Ras signalling pathway in human breast cancer cells overexpressing erbB-2.

    abstract：:The c-erbB-2 proto-oncogene encodes a receptor tyrosine kinase (RTK) closely related to the epidermal growth factor receptor (EGFR). Overexpression of erbB-2 occurs in approximately 20% of human breast tumours, where increased expression correlates with poor patient prognosis. The EGFR is coupled to the Ras signalling...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Janes PW,Daly RJ,deFazio A,Sutherland RL

    更新日期：1994-12-01 00:00:00

  • Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein.

    abstract：:The PLZF gene was identified first by its fusion with the retinoic acid receptor alpha gene in the t(11;17) translocation associated with a retinoic acid resistant form of acute promyelocytic leukemia (APL). It encodes a krüppel-like zinc finger protein with a POZ domain shared with a subset of regulatory proteins inc...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1202043

    authors： David G,Alland L,Hong SH,Wong CW,DePinho RA,Dejean A

    更新日期：1998-05-14 00:00:00

  • The concerted regulatory functions of the transcription factors nuclear factor-1 and upstream stimulatory factor on a composite element in the promoter of the hepatocyte growth factor gene.

    abstract：:Hepatocyte growth factor (HGF) is an important multifunctional cytokine whose gene expression is regulated mainly at the transcriptional level. Previous studies using transgenic mice as well as in vitro analyses showed that a potential regulatory element(s) exists between -260 to -230 bp in the upstream region of the ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1203581

    authors： Jiang JG,Gao B,Zarnegar R

    更新日期：2000-05-25 00:00:00

  • Efficient replication of plasmids containing the SV40 origin in N-myc overexpressing human neuroblastoma cells.

    abstract：:Using test plasmids containing the SV40 origin, we found a wide spectrum of permissiveness to their replication in different human cell lines. N-myc overexpressing neuroblastoma cells were highly permissive. LA-N-1 neuroblastoma cells were the most permissive of all the cell lines that we tested including the homologo...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Lee NG,Yamaguchi J,Subramanian KN

    更新日期：1991-07-01 00:00:00

  • Androgen regulation of soluble guanylyl cyclasealpha1 mediates prostate cancer cell proliferation.

    abstract：:The growth and progression of prostate cancer are dependent on androgens and androgen receptor (AR), which act by modulating gene expression. Utilizing a gene microarray approach, we have identified the alpha1-subunit gene of soluble guanylyl cyclase (sGC) as a novel androgen-regulated gene. A heterodimeric cytoplasmi...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1209956

    authors： Cai C,Chen SY,Zheng Z,Omwancha J,Lin MF,Balk SP,Shemshedini L

    更新日期：2007-03-08 00:00:00

  • Enhanced expression of vascular endothelial growth factor (VEGF) plays a critical role in the tumor progression potential induced by simian virus 40 large T antigen.

    abstract：:Vascular endothelial growth factor (VEGF), an important angiogenic factor, regulates cell proliferation, differentiation, and apoptosis through activation of its tyrosine-kinase receptors, such as Flt-1 and Flk-1/Kdr. Human malignant mesothelioma cells (HMC), which have wild-type p53, express VEGF and exhibit cell gro...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1205382

    authors： Catalano A,Romano M,Martinotti S,Procopio A

    更新日期：2002-04-25 00:00:00

  • Nucleocytoplasmic transport of HTLV-1 RNA is regulated by two independent LTR encoded nuclear retention elements.

    abstract：:Appropriate expression of HTLV-1 genes requires transcriptional transactivation by Tax and post-transcriptional regulation by Rex, both mediated by LTR encoded RNA sequences. Using a combination of deletion mutagenesis, Rex-reporter CAT assays, fluorescence in situ hybridization (FISH) and confocal laser scanning micr...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1201884

    authors： King JA,Bridger JM,Löchelt M,Lichter P,Schulz TF,Schirrmacher V,Khazaie K

    更新日期：1998-06-25 00:00:00

  • Characterization of the region of the short arm of chromosome 8 amplified in breast carcinoma.

    abstract：:Chromosomal region 8p11.2-p12 is consistently amplified in human breast cancer. We have constructed a 2.8 Mb YAC contig of this region, centered on the human Fibroblast Growth Factor Receptor 1 (FGFR1) locus and encompassing the Adrenergic beta 3 Receptor (ADRB3) locus. A smaller centromeric YAC contig spanning 1.4 Mb...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Dib A,Adélaïde J,Chaffanet M,Imbert A,Le Paslier D,Jacquemier J,Gaudray P,Theillet C,Birnbaum D,Pébusque MJ

    更新日期：1995-03-02 00:00:00

  • Cloning and characterization of a novel gene encoding a putative transmembrane protein with altered expression in some human transformed and tumor-derived cell lines.

    abstract：:Identification and characterization of genes expressed in normal cells and decreased in their malignant counterparts is an important method for detecting candidate tumor suppressors. Using differential display of mRNAs from nontumorigenic infinite life span human fibroblast cell strain MSU-1.1 and an isogenic fibrosar...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1202290

    authors： Qing J,Wei D,Maher VM,McCormick JJ

    更新日期：1999-01-14 00:00:00

  • Functional localization of a melanoma tumor suppressor gene to a small (< or = 2 Mb) region on 11q23.

    abstract：:We have previously demonstrated the existence of a melanoma tumor suppressor gene(s) on the long arm of chromosome 11 through suppression of tumorigenicity assays. Although loss of heterozygosity studies also support this finding, only a large critical region (44 cM) has been identified to date on 11q22-25. To further...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1202664

    authors： Robertson GP,Goldberg EK,Lugo TG,Fountain JW

    更新日期：1999-05-20 00:00:00

  • Induction of hepatocyte proliferation and liver hyperplasia by the targeted expression of cyclin E and skp2.

    abstract：:Cells in culture become competent to replicate in the absence of growth factor after progressing beyond the late G1 restriction point, suggesting that a set of genes expressed during G1 phase is sufficient to trigger completion of the cell cycle. However, this has not been demonstrated in an in vivo system. In this st...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1204248

    authors： Nelsen CJ,Hansen LK,Rickheim DG,Chen C,Stanley MW,Krek W,Albrecht JH

    更新日期：2001-04-05 00:00:00

  • The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding.

    abstract：:The BTB/POZ family of proteins has been implicated in multiple biological processes, including tumourigenesis, DNA damage responses and cell cycle progression and development. MIZ-1 (Myc-interacting zinc-finger protein 1) is known to activate transcription of CDKN1A. We recently found that a kidney cancer-related POK ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2011.331

    authors： Lee KM,Choi WI,Koh DI,Kim YJ,Jeon BN,Yoon JH,Lee CE,Kim SH,Oh J,Hur MW

    更新日期：2012-03-15 00:00:00