当前位置： SCI文献检索 > ONCOGENE期刊下所有文献 > NCOA5 deficiency promotes a unique liver protumorigenic microenvironment through p21WAF1/CIP1 overexpression, which is reversed by metformin.

NCOA5 deficiency promotes a unique liver protumorigenic microenvironment through p21WAF1/CIP1 overexpression, which is reversed by metformin.

Abstract：

:Prevention and treatment options for hepatocellular carcinoma (HCC) are presently limited, underscoring the necessity for further elucidating molecular mechanisms underlying HCC development and identifying new prevention and therapeutic targets. Here, we demonstrate a unique protumorigenic niche in the livers of Ncoa5+/- mouse model of HCC, which is characterized by altered expression of a subset of genes including p21WAF1/CIP1 and proinflammatory cytokine genes, increased putative hepatic progenitors, and expansions of activated and tissue-resident memory (TRM) CD8+ T lymphocytes, myeloid-derived suppressor cells (MDSCs), and alternatively activated M2 macrophages. Importantly, prophylactic metformin treatment reversed these characteristics including aberrant p21WAF1/CIP1 expression and subsequently reduced HCC incidence in Ncoa5+/- male mice. Heterozygous deletion of the p21WAF1/CIP1 gene alleviated the key features associated with the protumorigenic niche in the livers of Ncoa5+/- male mice. Moreover, transcriptomic analysis reveals that preneoplastic livers of Ncoa5+/- mice are similar to the livers of nonalcoholic steatohepatitis patients as well as the adjacent noncancerous liver tissues of a subset of HCC patients with a relatively poor prognosis. Together, our results suggest that p21WAF1/CIP1 overexpression is essential in the development of protumorigenic microenvironment induced by NCOA5 deficiency and metformin prevents HCC development via alleviating p21WAF1/CIP1 overexpression and protumorigenic microenvironment.

journal_name

Oncogene

journal_title

Oncogene

authors

Williams M,Liu X,Zhang Y,Reske J,Bahal D,Gohl TG,Hollern D,Ensink E,Kiupel M,Luo R,Das R,Xiao H

doi

10.1038/s41388-020-1256-x

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

3821-3836

issue

19

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-020-1256-x

journal_volume

39

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • 2-deoxyglucose-induced toxicity is regulated by Bcl-2 family members and is enhanced by antagonizing Bcl-2 in lymphoma cell lines.

    abstract：:Targeting altered cancer cell metabolism with the glycolysis inhibitor, 2-deoxyglucose (2DG), is a viable therapeutic strategy, but the effects of 2DG on lymphoma cells and the mechanism of action are unknown. Five T-cell lymphoma lines and two B-cell lymphoma lines were shown to be highly sensitive to 2DG. Examinatio...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2011.454

    authors： Zagorodna O,Martin SM,Rutkowski DT,Kuwana T,Spitz DR,Knudson CM

    更新日期：2012-05-31 00:00:00

  • A new candidate site for a tumor suppressor gene involved in mouse thymic lymphomagenesis is located on the distal part of chromosome 4.

    abstract：:In a previous work we provided preliminary evidence of the existence of a putative tumor suppressor gene region on the distal part of chromosome 4 in gamma-radiation-induced T-cell lymphomas of (C57BL/6J x RF/J) F1 hybrid mice. This region, named as TLSR2 (Thymic Lymphoma Suppressor Region 2), was located centered at ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1202009

    authors： Santos J,Herranz M,Pérez de Castro I,Pellicer A,Fernández-Piqueras J

    更新日期：1998-08-20 00:00:00

  • Infectivity and expression of the early adenovirus proteins are important regulators of wild-type and DeltaE1B adenovirus replication in human cells.

    abstract：:An adenovirus mutant lacking the expression of the large E1B protein (DeltaE1B) has been reported to replicate selectively in cells lacking the expression of functionally wild-type (wt) p53. Based on these results the DeltaE1B or ONYX-015 virus has been proposed to be an oncolytic virus which might be useful to treat ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1202886

    authors： Steegenga WT,Riteco N,Bos JL

    更新日期：1999-09-09 00:00:00

  • The biology and clinical significance of acquired genomic copy number aberrations and recurrent gene mutations in chronic lymphocytic leukemia.

    abstract：:Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and remains incurable with conventional chemotherapy treatment approaches. CLL as a disease entity is defined by a relatively parsimonious set of diagnostic criteria and therefore likely constitutes an umbrella term for multiple relate...

    journal_title：Oncogene

    pub_type： 杂志文章,评审

    doi：10.1038/onc.2012.411

    authors： Malek SN

    更新日期：2013-06-06 00:00:00

  • The myxoid liposarcoma FUS-DDIT3 fusion oncoprotein deregulates NF-kappaB target genes by interaction with NFKBIZ.

    abstract：:FUS (also called TLS), EWSR1 and TAF15 (also called TAF2N) are related genes involved in tumor type-specific fusion oncogenes in human malignancies. The FUS-DDIT3 fusion oncogene results from a t(12;16)(q13;p11) chromosome translocation and has a causative role in the initiation of myxoid/round cell liposarcomas (MLS/...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2008.378

    authors： Göransson M,Andersson MK,Forni C,Ståhlberg A,Andersson C,Olofsson A,Mantovani R,Aman P

    更新日期：2009-01-15 00:00:00

  • UVB-induced COX-2 expression requires histone H3 phosphorylation at Ser10 and Ser28.

    abstract：:Cyclooxygenase-2 (COX-2) is an inducible enzyme that contributes to the generation of chronic inflammation in response to chemical carcinogens and environmental stresses, including ultraviolet B (UVB) irradiation. Although post-translational histone modifications are believed to have an important role in modulating tr...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2012.71

    authors： Keum YS,Kim HG,Bode AM,Surh YJ,Dong Z

    更新日期：2013-01-24 00:00:00

  • Analysis of the neurofibromatosis type 1 (NF1) GAP-related domain by site-directed mutagenesis.

    abstract：:The gene for von Recklinghausen neurofibromatosis type 1 (NF1) was recently identified by positional cloning and found to encode a protein with sequence similarity to a family of eucaryotic GTPase-activating proteins (GAPs). Expression of the NF1-GAP-related domain (NF1GRD) has been shown to complement yeast strains d...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Gutmann DH,Boguski M,Marchuk D,Wigler M,Collins FS,Ballester R

    更新日期：1993-03-01 00:00:00

  • Overexpression of wild-type p53 interferes with normal development in Xenopus laevis embryos.

    abstract：:We have cloned and sequenced a Xenopus p53 homologue which differs by one amino acid deletion from a previously published Xenopus sequence (Soussi et al., 1987). Transcription analysis revealed that this gene is activated during early oogenesis and that zygotic transcription initiates after midblastula transition. Tra...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Hoever M,Clement JH,Wedlich D,Montenarh M,Knöchel W

    更新日期：1994-01-01 00:00:00

  • Loss of p53 induces leukemic transformation in a murine model of Jak2 V617F-driven polycythemia vera.

    abstract：:As leukemic transformation of myeloproliferative neoplasms (MPNs) worsens the clinical outcome, reducing the inherent risk of the critical event in MPN cases could be beneficial. Among genetic alterations concerning the transformation, the frequent one is TP53 mutation. Here we show that retroviral overexpression of J...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2016.478

    authors： Tsuruta-Kishino T,Koya J,Kataoka K,Narukawa K,Sumitomo Y,Kobayashi H,Sato T,Kurokawa M

    更新日期：2017-06-08 00:00:00

  • Expression and phenotypic alterations caused by an inducible transforming ras oncogene introduced into rat liver epithelial cells.

    abstract：:Although transforming ras oncogenes have been implicated as causative factors in liver cell transformation, the exact function and phenotypic alterations generated by the expression of such transforming genes in liver epithelial cells has yet to be defined. We have utilized a retroviral vector system to deliver an ind...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Huber BE,Cordingley MG

    更新日期：1988-09-01 00:00:00

  • Sensitization of pancreatic carcinoma cells for gamma-irradiation-induced apoptosis by XIAP inhibition.

    abstract：:Resistance of pancreatic cancer to current treatments including radiotherapy remains a major challenge in oncology and may be caused by defects in apoptosis programs. Since 'inhibitor of apoptosis proteins' (IAPs) block apoptosis at the core of the apoptotic machinery by inhibiting caspases, therapeutic modulation of ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1210502

    authors： Giagkousiklidis S,Vellanki SH,Debatin KM,Fulda S

    更新日期：2007-10-25 00:00:00

  • Proteins kinase Cɛ is required for non-small cell lung carcinoma growth and regulates the expression of apoptotic genes.

    abstract：:Protein kinase C (PKC)ɛ, a member of the novel PKC family, has key roles in mitogenesis and survival in normal and cancer cells. PKCɛ is frequently overexpressed in epithelial cancers, particularly in lung cancer. Using a short-hairpin RNA approach, here we established that PKCɛ is required for non-small cell lung car...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2011.428

    authors： Caino MC,Lopez-Haber C,Kim J,Mochly-Rosen D,Kazanietz MG

    更新日期：2012-05-17 00:00:00

  • Different interactions of Grb2/Ash molecule with the NGF and EGF receptors in rat pheochromocytoma PC12 cells.

    abstract：:We have previously shown that nerve growth factor (NGF) induces a rapid and relatively continuous activation of Ras in rat pheochromocytoma PC12 cells while epidermal growth factor (EGF) activates Ras transiently, and that tyrosine kinase activity of the NGF receptor is essential for the activation of Ras (Muroya et a...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Hashimoto Y,Matuoka K,Takenawa T,Muroya K,Hattori S,Nakamura S

    更新日期：1994-03-01 00:00:00

  • Expression of Brca1 and splice variant Brca1delta11 RNA levels in mouse mammary gland during normal development and tumorigenesis.

    abstract：:Expression of Brca1 in mouse mammary cancer has yet to be analysed. We use a progressive model of neoplasia based on several mouse epithelial cell lines that represent distinct steps toward the fully tumorigenic state. Using RNase protection analysis because acceptable anti-Brca1 antibodies are not available we invest...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1203905

    authors： Mixon M,Kittrell F,Medina D

    更新日期：2000-11-02 00:00:00

  • Adenosine A1 receptor, a target and regulator of estrogen receptoralpha action, mediates the proliferative effects of estradiol in breast cancer.

    abstract：:Estrogen receptor-alpha (ERalpha) and its ligand estradiol (E2) has critical roles in breast cancer growth and are key therapeutic targets. In this study, we report a novel dual role of the adenosine A1 receptor (Adora1) as an E2/ERalpha target and a regulator of ERalpha transcriptional activity. In ERalpha-positive b...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2009.409

    authors： Lin Z,Yin P,Reierstad S,O'Halloran M,Coon VJ,Pearson EK,Mutlu GM,Bulun SE

    更新日期：2010-02-25 00:00:00

  • Transformation by Hras(G12V) is consistently associated with mutant allele copy gains and is reversed by farnesyl transferase inhibition.

    abstract：:RAS-driven malignancies remain a major therapeutic challenge. The two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-o-tetradecanoylphorbol-13-acetate (TPA) model of mouse skin carcinogenesis has been used to study mechanisms of epithelial tumor development by oncogenic Hras. We used mice with an Hras(G12V) knock-in a...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2013.489

    authors： Chen X,Makarewicz JM,Knauf JA,Johnson LK,Fagin JA

    更新日期：2014-11-20 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

  • The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma.

    abstract：:The REL gene, encoding the NF-κB subunit c-Rel, is frequently amplified in B-cell lymphoma and functions as a tumour-promoting transcription factor. Here we report the surprising result that c-rel-/- mice display significantly earlier lymphomagenesis in the c-Myc driven, Eμ-Myc model of B-cell lymphoma. c-Rel loss als...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2015.399

    authors： Hunter JE,Butterworth JA,Zhao B,Sellier H,Campbell KJ,Thomas HD,Bacon CM,Cockell SJ,Gewurz BE,Perkins ND

    更新日期：2016-06-30 00:00:00

  • Deletions of the p16 gene in pediatric leukemia and corresponding cell lines.

    abstract：:The p16 gene (MTS1 or CDK4I) encoding an inhibitor of cyclin-dependent kinase 4 (cdk4), has been reported to be deleted in various tumor cell lines, including lines derived from leukemic cells. The reported frequency of p16 gene loss is much higher in established cell lines than in primary tumor specimens. We investig...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Kees UR,Ranford PR,Hatzis M

    更新日期：1996-05-16 00:00:00

  • Recurrent allelic deletions at mouse chromosomes 4 and 14 in Myc-induced liver tumors.

    abstract：:Transgenic mice expressing the c-Myc oncogene driven by woodchuck hepatitis virus (WHV) regulatory sequences develop hepatocellular carcinoma with a high frequency. To investigate genetic lesions that cooperate with Myc in liver carcinogenesis, we conducted a genome-wide scan for loss of heterozygosity (LOH) and mutat...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1205208

    authors： Wu Y,Renard CA,Apiou F,Huerre M,Tiollais P,Dutrillaux B,Buendia MA

    更新日期：2002-02-28 00:00:00

  • Cucurbitacin Q: a selective STAT3 activation inhibitor with potent antitumor activity.

    abstract：:Constitutive activation of the JAK/STAT3 pathway is a major contributor to oncogenesis. In the present study, structure-activity relationship (SAR) studies with five cucurbitacin (Cuc) analogs, A, B, E, I, and Q, led to the discovery of Cuc Q, which inhibits the activation of STAT3 but not JAK2; Cuc A which inhibits J...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1208470

    authors： Sun J,Blaskovich MA,Jove R,Livingston SK,Coppola D,Sebti SM

    更新日期：2005-05-05 00:00:00

  • The chromosomal translocation t(X;14)(q28;q11) in T-cell pro-lymphocytic leukaemia breaks within one gene and activates another.

    abstract：:Chromosomal translocation t(X;14)(q28;q11) has been observed in patients with pro-lymphocytic T-cell leukaemia (T-PLL). In two cases of T-PLL, one of which was associated with Ataxia telangiectasia (AT), the chromosomal break occurred in two different introns of a gene c6.1A, located at the Xq28 locus. Fusion transcri...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Fisch P,Forster A,Sherrington PD,Dyer MJ,Rabbitts TH

    更新日期：1993-12-01 00:00:00

  • Four tissue-specific mouse ltk mRNAs predict tyrosine kinases that differ upstream of their transmembrane segment.

    abstract：:Two alternatively spliced mouse lymphocyte and brain ltk cDNAs predict small transmembrane tyrosine kinases that use CUG translational start codons and that differ upstream of their transmembrane segment. A recently isolated human neuroblastoma ltk cDNA, in contrast, includes a regular AUG start codon and predicts a m...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Snijders AJ,Haase VH,Bernards A

    更新日期：1993-01-01 00:00:00

  • Association of a functional tandem repeats in the downstream of human telomerase gene and lung cancer.

    abstract：:Chemoprevention has been widely explored as a promising strategy for controlling the incidence of lung cancer, the leading cause of cancer-related death. To maximize the benefit of lung cancer chemoprevention, it is important to identify individuals at high risk for the disease. The genetic background has been shown t...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1206852

    authors： Wang L,Soria JC,Chang YS,Lee HY,Wei Q,Mao L

    更新日期：2003-10-16 00:00:00

  • The EBV-encoded LMP1 protein inhibits p53-triggered apoptosis but not growth arrest.

    abstract：:We have previously shown that exogenous wild type p53 induces apoptosis in the Burkitt lymphoma line BL41 that carries endogenous mutant p53, using a temperature sensitive p53 construct expressed as mutant p53 at 37 degrees C and wild type p53 at 32 degrees C (Ramqvist et al., Oncogene, 8, 1495-1500, 1993). We also fo...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Okan I,Wang Y,Chen F,Hu LF,Imreh S,Klein G,Wiman KG

    更新日期：1995-09-21 00:00:00

  • RBMY, a male germ cell-specific RNA-binding protein, activated in human liver cancers and transforms rodent fibroblasts.

    abstract：:The RNA-binding motif (RRM) gene on Y chromosome (RBMY), encoding a male germ cell-specific RNA-binding protein associated with spermatogenesis, was found inserted by hepatitis B virus (HBV) DNA in one childhood hepatocellular carcinoma (HCC). This study is aimed to explore the oncogenic potential of the RBMY protein....

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1207773

    authors： Tsuei DJ,Hsu HC,Lee PH,Jeng YM,Pu YS,Chen CN,Lee YC,Chou WC,Chang CJ,Ni YH,Chang MH

    更新日期：2004-07-29 00:00:00

  • Role for c-Abl and p73 in the radiation response of male germ cells.

    abstract：:p53 plays a central role in the induction of apoptosis of spermatogonia in response to ionizing radiation. In p53(-/-) testes, however, spermatogonial apoptosis still can be induced by ionizing radiation, so p53 independent apoptotic pathways must exist in spermatogonia. Here we show that the p53 homologues p63 and p7...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1204568

    authors： Hamer G,Gademan IS,Kal HB,de Rooij DG

    更新日期：2001-07-19 00:00:00

  • Somatic in frame deletions not involving juxtamembranous cysteine residues strongly activate the RET proto-oncogene.

    abstract：:Somatic RET mutations have been identified in a variable proportion (about 30-70%) of sporadic Medullary Thyroid Carcinoma (MTC) cases. They are represented by the Met918Thr substitution (exon 16) typical of Multiple Endocrine Neoplasia type 2B (MEN2B) and, to a lesser extent, by nucleotide changes occurring at one of...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1201079

    authors： Ceccherini I,Pasini B,Pacini F,Gullo M,Bongarzone I,Romei C,Santamaria G,Matera I,Mondellini P,Scopsi L,Pinchera A,Pierotti MA,Romeo G

    更新日期：1997-05-29 00:00:00

  • Intermediate filament dynamics and breast cancer: aberrant promoter methylation of the Synemin gene is associated with early tumor relapse.

    abstract：:Synemin (SYNM) is a type IV intermediate filament that has recently been shown to interact with the LIM domain protein zyxin, thereby possibly modulating cell adhesion and cell motility. Owing to this multiplicity of potential functions relevant to cancer development, we initiated a study to decipher SYNM expression a...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2010.229

    authors： Noetzel E,Rose M,Sevinc E,Hilgers RD,Hartmann A,Naami A,Knüchel R,Dahl E

    更新日期：2010-08-26 00:00:00

  • Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation.

    abstract：:Ras genes, frequently mutated in human tumors, promote malignant transformation. Ras transformation requires membrane anchorage, which is promoted by Ras farnesylcysteine carboxymethylester and by a second signal. Previously we showed that the farnesylcysteine mimetic, farnesylthiosalicylic acid (FTS) disrupts Ras mem...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1204950

    authors： Paz A,Haklai R,Elad-Sfadia G,Ballan E,Kloog Y

    更新日期：2001-11-08 00:00:00