Fstl1/DIP2A/MGMT signaling pathway plays important roles in temozolomide resistance in glioblastoma.

Abstract:

:Temozolomide was recognized as the first-line therapy for glioblastoma to prolong the survival of patients noticeably, while recent clinical studies found that some patients were not sensitive to temozolomide treatment. The possible mechanisms seemed to be methylguanine-DNA-methyltransferase (MGMT), mismatch repair, PARP, etc. And the abnormal expression of MGMT might be the most direct factor. In this study, we provide evidence that Fstl1 plays a vital role in temozolomide resistance by sequentially regulating DIP2A protein distribution, H3K9 acetylation (H3K9Ac), and MGMT transcription. As a multifunctional protein widely distributed in cells, DIP2A cooperates with the HDAC2-DMAP1 complex to enhance H3K9Ac deacetylation, prevent MGMT transcription, and increase temozolomide sensitivity. Fstl1, a glycoprotein highly expressed in glioblastoma, competitively binds DIP2A to block DIP2A nuclear translocation, so as to hinder DIP2A from binding the HDAC2-DMAP1 complex. The overexpression of Fstl1 promoted the expression of MGMT in association with increased promoter H3K9Ac. Upregulation of Fstl1 enhanced temozolomide resistance, whereas Fstl1 silencing obviously sensitized GBM cells to temozolomide both in vivo and in vitro. Moreover, DIP2A depletion abolished the effects of Fstl1 on MGMT expression and temozolomide resistance. These findings highlight an important role of Fstl1 in the regulation of temozolomide resistance by modulation of DIP2A/MGMT signaling.

journal_name

Oncogene

journal_title

Oncogene

authors

Nie E,Miao F,Jin X,Wu W,Zhou X,Zeng A,Yu T,Zhi T,Shi Z,Wang Y,Zhang J,Liu N,You Y

doi

10.1038/s41388-018-0596-2

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

2706-2721

issue

15

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-018-0596-2

journal_volume

38

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Clustered mutations in the second exon of the MYC gene in sporadic Burkitt's lymphoma.

    abstract::The primary tumors from 15 untreated patients with Burkitt's lymphoma were analysed for abnormalities in the coding region of the MYC gene by single stranded conformational polymorphism (SSCP) analysis followed by DNA sequencing. Fourteen of the 15 tumors had one or more clonal mutations. Forty one mutations were foun...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Yano T,Sander CA,Clark HM,Dolezal MV,Jaffe ES,Raffeld M

    更新日期:1993-10-01 00:00:00

  • A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40 kDa vasculostatin from tumor suppressor BAI1.

    abstract::Brain-specific angiogenesis inhibitor 1 (BAI1), an orphan G protein-coupled receptor-type seven transmembrane protein, was recently found mutated or silenced in multiple human cancers and can interfere with tumor growth when overexpressed. Yet, little is known about its regulation and the molecular mechanisms through ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.1

    authors: Cork SM,Kaur B,Devi NS,Cooper L,Saltz JH,Sandberg EM,Kaluz S,Van Meir EG

    更新日期:2012-12-13 00:00:00

  • Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase-3 in colon cancer cells.

    abstract::We have previously shown that the death receptor ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) induces an increase of intracellular C(16)-ceramide in sensitive SW480 but not in resistant SW620 cells. Resistance in SW620 cells was overcome by exogenous ceramide, leading us to propose that defec...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.468

    authors: White-Gilbertson S,Mullen T,Senkal C,Lu P,Ogretmen B,Obeid L,Voelkel-Johnson C

    更新日期:2009-02-26 00:00:00

  • Kinase activity-independent suppression of p73alpha by AMP-activated kinase alpha (AMPKalpha).

    abstract::Although p73alpha induces many of the same cellular events as p53, it is structurally distinct from p53 in that it possesses a unique COOH-terminal domain. To dissect the function of this domain, we performed yeast two-hybrid screening of a HeLa cDNA library using residues 552-636 of p73alpha as bait. Among the clones...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.452

    authors: Lee YG,Lee SW,Sin HS,Kim EJ,Um SJ

    更新日期:2009-02-19 00:00:00

  • Cloning, expression and chromosomal localization of a novel gene for protein tyrosine phosphatase (PTP-U2) induced by various differentiation-inducing agents.

    abstract::Previously, we cloned two gene fragments encoding novel protein tyrosine phosphatases, termed PTP-U1 and PTP-U2. Here, we report the full-length sequence, expression, and chromosomal localization of the PTP-U2 gene. The cDNA for PTP-U2, which was obtained from a human normal kidney library, predicts a protein of 1216 ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Seimiya H,Sawabe T,Inazawa J,Tsuruo T

    更新日期:1995-05-04 00:00:00

  • Hepatitis C virus-induced activation of β-catenin promotes c-Myc expression and a cascade of pro-carcinogenetic events.

    abstract::Chronic infection by hepatitis C virus (HCV) is a major risk factor for the onset and development of hepatocellular carcinoma (HCC), although the underlying mechanisms are unclear. The c-Myc oncogene contributes to the genesis of many types of cancers, including HCC, partly via the induction of genetic damage and the ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.484

    authors: Higgs MR,Lerat H,Pawlotsky JM

    更新日期:2013-09-26 00:00:00

  • CpG island promoter methylation and silencing of 14-3-3sigma gene expression in LNCaP and Tramp-C1 prostate cancer cell lines is associated with methyl-CpG-binding protein MBD2.

    abstract::14-3-3sigma proteins regulate numerous cellular processes that are important to cancer development. One of its biological roles involves G2 cell-cycle arrest following DNA damage. It has also been reported that the loss of 14-3-3sigma expression via CpG methylation may contribute to malignant transformation by impairi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209462

    authors: Pulukuri SM,Rao JS

    更新日期:2006-08-03 00:00:00

  • Carcinoma of the vulva: HPV and p53 mutations.

    abstract::Recent evidence suggests that squamous cell carcinoma of the vulva may have more than one etiology, with only some tumors associated with human papillomavirus (HPV). Cells infected with HPV produce a viral protein (E6) which binds to and causes rapid degradation of p53, possibly contributing to cellular transformation...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Lee YY,Wilczynski SP,Chumakov A,Chih D,Koeffler HP

    更新日期:1994-06-01 00:00:00

  • O-GlcNAcylation is involved in the transcriptional activity of EWS-FLI1 in Ewing's sarcoma.

    abstract::The oncogene EWS-FLI1 encodes a chimeric transcription factor expressed in Ewing's sarcoma family tumors (ESFTs). EWS-FLI1 target gene expression is thought to drive ESFT pathogenesis and, therefore, inhibition of EWS-FLI1 activity holds high therapeutic promise. As the activity of many transcription factors is regula...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.484

    authors: Bachmaier R,Aryee DN,Jug G,Kauer M,Kreppel M,Lee KA,Kovar H

    更新日期:2009-03-05 00:00:00

  • Crosstalk between the human papillomavirus E2 transcriptional activator and the E6 oncoprotein.

    abstract::Human papillomaviruses are the causative agents of cervical cancer. Previous studies have shown that loss of the viral E2 protein during malignant progression is an important feature of HPV-induced malignancy due to the resulting uncontrolled expression of the viral oncoproteins E6 and E7. We now show however that the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208701

    authors: Grm HS,Massimi P,Gammoh N,Banks L

    更新日期:2005-08-04 00:00:00

  • Dysregulated TRK signalling is a therapeutic target in CYLD defective tumours.

    abstract::Individuals with germline mutations in the tumour-suppressor gene CYLD are at high risk of developing disfiguring cutaneous appendageal tumours, the defining tumour being the highly organised cylindroma. Here, we analysed CYLD mutant tumour genomes by array comparative genomic hybridisation and gene expression microar...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.133

    authors: Rajan N,Elliott R,Clewes O,Mackay A,Reis-Filho JS,Burn J,Langtry J,Sieber-Blum M,Lord CJ,Ashworth A

    更新日期:2011-10-13 00:00:00

  • Human p53 binds DNA as a protein homodimer but monomeric variants retain full transcription transactivation activity.

    abstract::Wild-type human p53 protein is able to self-associate and consists predominantly of homotetramers in solution. In earlier work we identified the protein sequence motifs involved in p53 quaternary structure and showed that while monomeric p53 protein retains tumour suppressor function, monomeric tumour mutant p53 lacks...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Tarunina M,Jenkins JR

    更新日期:1993-11-01 00:00:00

  • Pim kinase-dependent inhibition of c-Myc degradation.

    abstract::Pim kinases are found to be highly expressed in leukemia, lymphoma, prostate and pancreatic cancer. Bitransgenic mice overexpressing either Pim-1 or Pim-2 and c-Myc succumb to pre-B-cell lymphoma at a strikingly accelerated speed. Despite that Pim-1/Pim-2 has long been recognized as a strong synergistic partner with c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.123

    authors: Zhang Y,Wang Z,Li X,Magnuson NS

    更新日期:2008-08-14 00:00:00

  • Future prospects for oncolytic therapy.

    abstract::Viruses have been engineered to replicate selectively in cancer cells, based on a number of innovative principles. Several of these viruses have entered clinical trials and have proven relatively safe, and have shown evidence of efficacy. However, further research is required to enable these agents to function systemi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209064

    authors: McCormick F

    更新日期:2005-11-21 00:00:00

  • Deletion mapping using quantitative real-time PCR identifies two distinct 3p21.3 regions affected in most cervical carcinomas.

    abstract::We report chromosome 3p deletion mapping of 32 cervical carcinoma (CC) biopsies using 26 microsatellite markers located in frequently deleted 3p regions to detect loss of heterozygosity and homozygous loss. In addition, two STS markers (NLJ-003 and NL3-001) located in the 3p21.3 telomeric (3p21.3T) and 3p21.3 centrome...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206429

    authors: Senchenko V,Liu J,Braga E,Mazurenko N,Loginov W,Seryogin Y,Bazov I,Protopopov A,Kisseljov FL,Kashuba V,Lerman MI,Klein G,Zabarovsky ER

    更新日期:2003-05-15 00:00:00

  • Ras-GAP SH3 domain binding protein (G3BP) is a modulator of USP10, a novel human ubiquitin specific protease.

    abstract::Degradation of cellular proteins through ubiquitination is a fundamental strategy for regulating biological pathways. De-ubiquitination, i.e. the removal of ubiquitin from proteins and peptides to which ubiquitin is attached, is catalyzed by processing proteases known as de-ubiquitinating enzymes. We are studying the ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204553

    authors: Soncini C,Berdo I,Draetta G

    更新日期:2001-06-28 00:00:00

  • Adenovirus-mediated overexpression of p14(ARF) induces p53 and Bax-independent apoptosis.

    abstract::The human INK4a gene locus encodes two structurally unrelated tumor suppressor proteins, p16(INK4a) and p14(ARF), which are frequently inactivated in human cancer. Whereas p16(INK4a) acts through engagement of the Rb-cdk4/6-cyclin D pathway, both the pro-apoptotic and cell cycle-regulatory functions of p14(ARF) were s...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205458

    authors: Hemmati PG,Gillissen B,von Haefen C,Wendt J,Stärck L,Güner D,Dörken B,Daniel PT

    更新日期:2002-05-09 00:00:00

  • Molecular requirements for transcriptional initiation of the murine c-myc gene.

    abstract::We have identified sequences in the 5' flanking region of the murine c-myc gene's P1 and P2 transcription initiation sites which form specific complexes with nuclear factors of murine and human origin and are also required for normal P1 and P2 usage. Four nuclear factor binding sites were identified within 400 bp 5' o...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Asselin C,Nepveu A,Marcu KB

    更新日期:1989-05-01 00:00:00

  • The hepatitis B virus X protein abrogates Bcl-2-mediated protection against Fas apoptosis in the liver.

    abstract::The role of the hepatitis B virus protein HBx in liver cell proliferation and apoptosis remains controversial. Using a transgenic mouse model, we have recently shown that HBx stimulates the apoptotic turnover of hepatocytes, independently of p53. In this paper, we tested whether the proapoptotic function of HBx can in...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205110

    authors: Terradillos O,de La Coste A,Pollicino T,Neuveut C,Sitterlin D,Lecoeur H,Gougeon ML,Kahn A,Buendia MA

    更新日期:2002-01-17 00:00:00

  • Cellular ITAM-containing proteins are oncoproteins in nonhematopoietic cells.

    abstract::Immunoreceptor tyrosine-based activation motifs (ITAMs) are involved in the transduction of signals necessary for activation, differentiation, and survival in hematopoietic cells. Several viruses have been shown to encode ITAM-containing transmembrane proteins. Although expression of these viral proteins has in some c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209296

    authors: Grande SM,Katz E,Crowley JE,Bernardini MS,Ross SR,Monroe JG

    更新日期:2006-05-04 00:00:00

  • Role of the BLT2, a leukotriene B4 receptor, in Ras transformation.

    abstract::Oncogenic Ras is known to drive both the Rac and Raf-MAP-kinase pathways, which act in concert to cause cell transformation. Unlike the Raf-MAP-kinase cascade, however, the downstream elements of Rac pathway are not fully understood. Previously, we showed that cytosolic phospholipase A2 (cPLA2) and subsequent metaboli...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208151

    authors: Yoo MH,Song H,Woo CH,Kim H,Kim JH

    更新日期:2004-12-09 00:00:00

  • An E mu-BCL-2 transgene facilitates leukaemogenesis by ionizing radiation.

    abstract::Clonogenic murine B cell precursors are normally ultrasensitive to apoptosis following genotoxic exposure in vitro but can be protected by expression of an E mu-BCL-2 transgene. Such exposures are likely to be mutagenic. This in turn suggests that a level of in vivo genotoxic exposure that usually has minimal patholog...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202721

    authors: Gibbons DL,MacDonald D,McCarthy KP,Cleary HJ,Plumb M,Wright EG,Greaves MF

    更新日期:1999-07-01 00:00:00

  • Src family kinases and HER2 interactions in human breast cancer cell growth and survival.

    abstract::Evidence from murine fibroblast models and human breast cancer cells indicates that c-Src and human EGF receptor (HER1) synergize to enhance neoplastic growth of mammary epithelial cells. To investigate whether interactions between c-Src and other HER family members may also play a role in breast tumor progression, we...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204205

    authors: Belsches-Jablonski AP,Biscardi JS,Peavy DR,Tice DA,Romney DA,Parsons SJ

    更新日期:2001-03-22 00:00:00

  • Rb inactivation accelerates neoplastic growth and substitutes for recurrent amplification of cIAP1, cIAP2 and Yap1 in sporadic mammary carcinoma associated with p53 deficiency.

    abstract::Genetically defined mouse models offer an important tool to identify critical secondary genetic alterations with relevance to human cancer pathogenesis. We used newly generated MMTV-Cre105Ayn mice to inactivate p53 and/or Rb strictly in the mammary epithelium, and to determine recurrent genomic changes associated with...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.300

    authors: Cheng L,Zhou Z,Flesken-Nikitin A,Toshkov IA,Wang W,Camps J,Ried T,Nikitin AY

    更新日期:2010-10-21 00:00:00

  • WAVE3, an actin-polymerization gene, is truncated and inactivated as a result of a constitutional t(1;13)(q21;q12) chromosome translocation in a patient with ganglioneuroblastoma.

    abstract::Neuroblastoma (Nb) is a malignancy of the sympathetic nervous system which affects children in their first decade. It is the most common extra-cranial solid tumor in children with an incidence of approximately 1 in 8-10 000 live births annually and accounts for approximately 10% of all children's cancers. Ganglioneuro...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205734

    authors: Sossey-Alaoui K,Su G,Malaj E,Roe B,Cowell JK

    更新日期:2002-08-29 00:00:00

  • Functional genomics identifies new synergistic therapies for retinoblastoma.

    abstract::Local intravitreal or intra-arterial chemotherapy has improved therapeutic success for the pediatric cancer retinoblastoma (RB), but toxicity remains a major caveat. RB initiates primarily with RB1 loss or, rarely, MYCN amplification, but the critical downstream networks are incompletely understood. We set out to unco...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-1372-7

    authors: Aubry A,Pearson JD,Huang K,Livne-Bar I,Ahmad M,Jagadeesan M,Khetan V,Ketela T,Brown KR,Yu T,Lu S,Wrana JL,Moffat J,Bremner R

    更新日期:2020-07-01 00:00:00

  • The serologically defined colon cancer antigen-3 interacts with the protein tyrosine phosphatase PTPN13 and is involved in the regulation of cytokinesis.

    abstract::Cytokinesis is the final step of cell division. Increasing evidence suggests failure of cytokinesis might contribute to the development of cancer. Here, we demonstrate that the serologically defined colon cancer antigen-3 (SDCCAG3) forms a complex with PTPN13, a protein tyrosine phosphatase known to be involved in the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.485

    authors: Hagemann N,Ackermann N,Christmann J,Brier S,Yu F,Erdmann KS

    更新日期:2013-09-26 00:00:00

  • CKIP-1 acts as a colonic tumor suppressor by repressing oncogenic Smurf1 synthesis and promoting Smurf1 autodegradation.

    abstract::Dysregulation of cellular signaling pathways can lead to colon cancer. However, research on the key signaling effectors or regulators in colon carcinogenesis is limited. Casein kinase-2 interacting protein-1 (CKIP-1; also known as PLEKHO1) is crucial during adult bone formation and is a promising drug target for osteo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.340

    authors: Nie J,Liu L,Xing G,Zhang M,Wei R,Guo M,Li X,Xie P,Li L,He F,Han W,Zhang L

    更新日期:2014-07-10 00:00:00

  • Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects.

    abstract::The checkpoint sliding-clamp complex, Rad9/Rad1/Hus1, plays a critical role during initiation of checkpoint signals in response to DNA damage and replication disruption. We investigated the impact of loss of Rad1 on checkpoint function and on DNA replication in mammalian cells. We show that RAD1 is an essential gene f...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207753

    authors: Bao S,Lu T,Wang X,Zheng H,Wang LE,Wei Q,Hittelman WN,Li L

    更新日期:2004-07-22 00:00:00

  • Loss of heterozygosity in human breast carcinomas in the ataxia telangiectasia, Cowden disease and BRCA1 gene regions.

    abstract::To appreciate the involvement of known or potential susceptibility genes in sporadic breast tumors, we have searched for chromosomal deletions by studying loss of heterozygosity (LOH) at 43 microsatellite (CA)n markers from human chromosomes 10, 11 and 17, in 115 unselected consecutive samples of breast carcinoma with...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1200818

    authors: Kerangueven F,Eisinger F,Noguchi T,Allione F,Wargniez V,Eng C,Padberg G,Theillet C,Jacquemier J,Longy M,Sobol H,Birnbaum D

    更新日期:1997-01-23 00:00:00