p21 suppresses inflammation and tumorigenesis on pRB-deficient stratified epithelia.

Abstract:

:The retinoblastoma gene product (pRb) controls proliferation and differentiation processes in stratified epithelia. Importantly, and in contrast to other tissues, Rb deficiency does not lead to spontaneous skin tumor formation. As the cyclin-dependent kinase inhibitor p21 regulates proliferation and differentiation in the absence of pRb, we analyzed the consequences of deleting p21 in pRb-ablated stratified epithelia (hereafter pRb(ΔEpi);p21-/-). These mice display an enhancement of the phenotypic abnormalities observed in pRb(ΔEpi) animals, indicating that p21 partially compensates pRb absence. Remarkably, pRb(ΔEpi);p21-/- mice show an acute skin inflammatory phenotype and develop spontaneous epithelial tumors, particularly affecting tongue and oral tissues. Biochemical analyses and transcriptome studies reveal changes affecting multiple pathways, including DNA damage and p53-dependent signaling responses. Comparative metagenomic analyses, together with the histopathological profiles, indicate that these mice constitute a faithful model for human head and neck squamous cell carcinomas. Collectively, our findings demonstrate that p21, in conjunction with pRb, has a central role in regulating multiple epithelial processes and orchestrating specific tumor suppressor functions.

journal_name

Oncogene

journal_title

Oncogene

authors

Saiz-Ladera C,Lara MF,Garín M,Ruiz S,Santos M,Lorz C,García-Escudero R,Martínez-Fernández M,Bravo A,Fernández-Capetillo O,Segrelles C,Paramio JM

doi

10.1038/onc.2013.417

subject

Has Abstract

pub_date

2014-09-11 00:00:00

pages

4599-4612

issue

37

eissn

0950-9232

issn

1476-5594

journal_volume

33

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Stabilization of prolactin receptor in breast cancer cells.

    abstract::The role of the hormone prolactin (PRL) in the pathogenesis of breast cancer is mediated by its cognate receptor (PRLr). Ubiquitin-dependent degradation of the PRLr that negatively regulates PRL signaling is triggered by PRL-mediated phosphorylation of PRLr on Ser349 followed by the recruitment of the beta-transducin ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209214

    authors: Li Y,Clevenger CV,Minkovsky N,Kumar KG,Raghunath PN,Tomaszewski JE,Spiegelman VS,Fuchs SY

    更新日期:2006-03-23 00:00:00

  • SYK interaction with ITGβ4 suppressed by Epstein-Barr virus LMP2A modulates migration and invasion of nasopharyngeal carcinoma cells.

    abstract::Epstein-Barr virus (EBV)-encoded Latent Membrane Protein 2A (LMP2A) is an EBV latency-associated protein regularly expressed in nasopharyngeal carcinoma (NPC). In B cells, LMP2A activity resembles that of a constitutively activated antigen receptor, which recruits the Syk tyrosine kinase to activate a set of downstrea...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.380

    authors: Zhou X,Matskova L,Rathje LS,Xiao X,Gish G,Werner M,Ignatyev I,Yu N,Zhao W,Tian F,Hou B,Zhang Z,Pawson T,Chen F,Ernberg I

    更新日期:2015-08-20 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

  • A subclass of tumor-inhibitory monoclonal antibodies to ErbB-2/HER2 blocks crosstalk with growth factor receptors.

    abstract::ErbB-2 is an orphan receptor that belongs to a family of tyrosine kinase receptors for either epidermal growth factor (EGF) or Neu differentiation factor (NDF/neuregulin). Because overexpression of the erbB-2 proto-oncogene is frequently associated with an aggressive clinical course of certain human adenocarcinomas, t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201029

    authors: Klapper LN,Vaisman N,Hurwitz E,Pinkas-Kramarski R,Yarden Y,Sela M

    更新日期:1997-05-01 00:00:00

  • Genome-wide mechanisms of Smad binding.

    abstract::A dual role of transforming growth factor β (TGF-β), to both suppress and promote tumor progression and metastasis, has been well established, but its molecular basis has remained elusive. In this review, we focus on Smad proteins, which are central mediators of the signal transduction of TGF-β family members. We desc...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2012.191

    authors: Morikawa M,Koinuma D,Miyazono K,Heldin CH

    更新日期:2013-03-28 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

  • The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis.

    abstract::Expression of viral proteins may result in susceptibility of cells to the cytotoxic effect of Tumor Necrosis Factor Alpha (TNF). While murine C127 cells containing the bovine papillomavirus type 1 (BPV-1) genome were reported to exhibit increased TNF sensitivity, the gene(s) responsible was not identified. The BPV-1 E...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202373

    authors: Rapp L,Liu Y,Hong Y,Androphy EJ,Chen JJ

    更新日期:1999-01-21 00:00:00

  • Molecular mechanism of cell cycle progression induced by the oncogene product Tax of human T-cell leukemia virus type I.

    abstract::The trans-activator protein Tax of human T-cell leukemia virus type I (HTLV-I) plays an important role in the development of adult T-cell leukemia through, at least in part, its ability to stimulate cell growth. We previously reported that Tax induced cell cycle progression from G0/G1 phase to S and G2/M phases in hum...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204304

    authors: Iwanaga R,Ohtani K,Hayashi T,Nakamura M

    更新日期:2001-04-19 00:00:00

  • Cyclooxygenase-2 (COX-2) inhibitors sensitize tumor cells specifically to death receptor-induced apoptosis independently of COX-2 inhibition.

    abstract::Cyclooxygenase-2 (COX-2) is involved in diverse processes such as inflammation, carcinogenesis and apoptosis. As COX-2 inhibitors interfere with these processes, inhibition of COX-2 has been suggested as a promising anticancer treatment. However, the role of COX-2 in modulation of apoptosis as well as the death pathwa...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206837

    authors: Totzke G,Schulze-Osthoff K,Jänicke RU

    更新日期:2003-09-11 00:00:00

  • MicroRNAs as potential cancer therapeutics.

    abstract::MicroRNAs (miRNAs) have been shown to have an important role in various cellular processes, such as apoptosis, differentiation and development. Recent studies have shown that miRNAs are mis-expressed in human cancers where they can exert their effect as oncogenes or tumor suppressors. Here, we review the potential for...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2009.353

    authors: Trang P,Weidhaas JB,Slack FJ

    更新日期:2008-12-01 00:00:00

  • Evaluation of novel cell cycle inhibitors in mantle cell lymphoma.

    abstract::Signature abnormalities in the cell cycle and apoptotic pathway have been identified in mantle cell lymphoma (MCL), affording the opportunity to develop targeted therapies. In this study, we tested a novel class of kinase inhibitors, styryl sulfones, which differ from prior cell cycle inhibitors in that they are not r...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210350

    authors: Park IW,Reddy MV,Reddy EP,Groopman JE

    更新日期:2007-08-16 00:00:00

  • Transforming growth factor-beta 1 inhibits cyclin D1 expression in intestinal epithelial cells.

    abstract::Transforming growth factor-beta 1 (TGF-beta 1) inhibits most epithelial cell types by blocking cell cycle progression during the G1 phase. D cyclins are normally expressed during G1 and are regulators of G1 progression. One of the crucial functions of D cyclins is their ability to bind to a cyclin-dependent kinase (Cd...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Ko TC,Sheng HM,Reisman D,Thompson EA,Beauchamp RD

    更新日期:1995-01-05 00:00:00

  • SYT7 acts as a driver of hepatic metastasis formation of gastric cancer cells.

    abstract::Liver metastasis remains a serious problem in the management of gastric cancer (GC). Our aims were to identify through transcriptome analysis a molecule that mediates hepatic metastasis in GC, and to evaluate its potential as a diagnostic marker and a therapeutic target. The effects of knocking out a relevant molecule...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-018-0335-8

    authors: Kanda M,Tanaka H,Shimizu D,Miwa T,Umeda S,Tanaka C,Kobayashi D,Hattori N,Suenaga M,Hayashi M,Iwata N,Yamada S,Fujiwara M,Kodera Y

    更新日期:2018-09-01 00:00:00

  • Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes.

    abstract::Antioxidant response element (ARE)-mediated expression and coordinated induction of genes encoding detoxifying enzymes is one mechanism of critical importance to cellular protection against oxidative stress. In the present report, we demonstrate that nuclear transcription factors Nrf2 and Nrf1 associate with Jun (c-Ju...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202237

    authors: Venugopal R,Jaiswal AK

    更新日期:1998-12-17 00:00:00

  • LncRNA-mediated regulation of cell signaling in cancer.

    abstract::To date, a large number of long non-coding RNAs (lncRNAs) have been recently discovered through functional genomics studies. Importantly, lncRNAs have been shown, in many cases, to function as master regulators for gene expression and thus, they can play a critical role in various biological functions and disease proc...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2017.184

    authors: Peng WX,Koirala P,Mo YY

    更新日期:2017-10-12 00:00:00

  • Upregulation of histamine receptor H1 promotes tumor progression and contributes to poor prognosis in hepatocellular carcinoma.

    abstract::H1 histamine receptor (H1HR) belongs to the family of rhodopsin-like G-protein-coupled receptors. Recent studies have shown that H1HR expression is increased in several types of cancer. However, its functional roles in tumor progression remain largely unknown, especially in hepatocellular carcinoma (HCC). We found tha...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-1093-y

    authors: Zhao J,Hou Y,Yin C,Hu J,Gao T,Huang X,Zhang X,Xing J,An J,Wan S,Li J

    更新日期:2020-02-01 00:00:00

  • The interaction between caveolin-1 and Rho-GTPases promotes metastasis by controlling the expression of alpha5-integrin and the activation of Src, Ras and Erk.

    abstract::Proteins containing a caveolin-binding domain (CBD), such as the Rho-GTPases, can interact with caveolin-1 (Cav1) through its caveolin scaffold domain. Rho-GTPases are important regulators of p130(Cas), which is crucial for both normal cell migration and Src kinase-mediated metastasis of cancer cells. However, althoug...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.288

    authors: Arpaia E,Blaser H,Quintela-Fandino M,Duncan G,Leong HS,Ablack A,Nambiar SC,Lind EF,Silvester J,Fleming CK,Rufini A,Tusche MW,Brüstle A,Ohashi PS,Lewis JD,Mak TW

    更新日期:2012-02-16 00:00:00

  • Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells.

    abstract::Caveolin-1 is an essential structural constituent of caveolae that has been implicated in mitogenic signaling and oncogenesis. Caveolin-1 is down-regulated in oncogene-transformed and tumor-derived cells. Antisense suppression of caveolin-1 or expression of a dominant negative form are sufficient for inducing cellular...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205300

    authors: Fiucci G,Ravid D,Reich R,Liscovitch M

    更新日期:2002-04-04 00:00:00

  • Transcriptional regulation of A33 antigen expression by gut-enriched Krüppel-like factor.

    abstract::A33 antigen is a membrane-bound protein that is expressed only in intestinal epithelium and in most human colon cancers. Thus, A33 antigen has been explored as a potential therapeutic target for the treatment of colon cancers. However, little is known about the mechanism responsible for the tissue-specific pattern of ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206508

    authors: Mao Z,Song S,Zhu Y,Yi X,Zhang H,Shang Y,Tong T

    更新日期:2003-07-10 00:00:00

  • NFATc2 is an intrinsic regulator of melanoma dedifferentiation.

    abstract::Melanoma dedifferentiation, characterized by the loss of MITF and MITF regulated genes and by upregulation of stemness markers as CD271, is implicated in resistance to chemotherapy, target therapy and immunotherapy. The identification of intrinsic mechanisms fostering melanoma dedifferentiation may provide actionable ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.355

    authors: Perotti V,Baldassari P,Molla A,Vegetti C,Bersani I,Maurichi A,Santinami M,Anichini A,Mortarini R

    更新日期:2016-06-02 00:00:00

  • AP2α controls the dynamic balance between miR-126&126* and miR-221&222 during melanoma progression.

    abstract::Accumulating evidences have shown the association between aberrantly expressed microRNAs (miRs) and cancer, where these small regulatory RNAs appear to dictate the cell fate by regulating all the main biological processes. We demonstrated the responsibility of the circuitry connecting the oncomiR-221&222 with the tumo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.357

    authors: Felli N,Errico MC,Pedini F,Petrini M,Puglisi R,Bellenghi M,Boe A,Felicetti F,Mattia G,De Feo A,Bottero L,Tripodo C,Carè A

    更新日期:2016-06-09 00:00:00

  • Translation of p15.5INK4B, an N-terminally extended and fully active form of p15INK4B, is initiated from an upstream GUG codon.

    abstract::The expression of the cyclin-dependent kinase inhibitor p15INK4B in normal cells after induction with TGF-beta1, or following overexpression from an adenovirus-encoded cDNA, appears on an SDS-polyacrylamide gel as a doublet. Here, the underlying mechanism behind the synthesis of the two species has been studied. By ex...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203496

    authors: Fuxe J,Raschperger E,Pettersson RF

    更新日期:2000-03-23 00:00:00

  • Function for p300 and not CBP in the apoptotic response to DNA damage.

    abstract::The cellular response to ionizing radiation (IR) includes the induction of apoptosis. The p300/CBP proteins possess histone acetyltransferase activity and function as transcriptional coactivators of p53. We have prepared cells deficient in p300 or CBP to define the roles of these proteins in the cellular response to D...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202930

    authors: Yuan ZM,Huang Y,Ishiko T,Nakada S,Utsugisawa T,Shioya H,Utsugisawa Y,Shi Y,Weichselbaum R,Kufe D

    更新日期:1999-10-07 00:00:00

  • Regulation of Pax3 transcriptional activity by SUMO-1-modified PML.

    abstract::Pax3 is an evolutionarily conserved transcription factor that plays a major role in a variety of developmental processes. Mutations in Pax3 lead to severe malformations as seen in human Waardenburg syndrome and in the Splotch mutant mice. The transcriptional activity of Pax3 was recently shown to be repressed by Daxx ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204063

    authors: Lehembre F,Müller S,Pandolfi PP,Dejean A

    更新日期:2001-01-04 00:00:00

  • The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development.

    abstract::Graft versus host disease (GvHD), which is the primary complication of allogeneic bone marrow transplantation, can alter the intestinal barrier targeted by activated donor T-cells. Chemical inhibition of the stress protein HSP90 was demonstrated in vitro to inhibit T-cell activation and to modulate endoplasmic reticul...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.242

    authors: Joly AL,Deepti A,Seignez A,Goloudina A,Hebrard S,Schmitt E,Richaud S,Fourmaux E,Hammann A,Collura A,Svrcek M,Jego G,Robinet E,Solary E,Demidov O,Kohli E,Garrido C

    更新日期:2016-06-02 00:00:00

  • The pro-metastatic protein anterior gradient-2 predicts poor prognosis in tamoxifen-treated breast cancers.

    abstract::Transcriptomic screens in breast cancer cell lines have identified a protein named anterior gradient-2 (AGR2) as a potentially novel oncogene overexpressed in estrogen receptor (ER) positive tumours. As targeting the ER is responsible for major improvements in cure rates and prevention of breast cancers, we have evalu...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.228

    authors: Hrstka R,Nenutil R,Fourtouna A,Maslon MM,Naughton C,Langdon S,Murray E,Larionov A,Petrakova K,Muller P,Dixon MJ,Hupp TR,Vojtesek B

    更新日期:2010-08-26 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

  • Epigenetic loss of AOX1 expression via EZH2 leads to metabolic deregulations and promotes bladder cancer progression.

    abstract::Advanced Bladder Cancer (BLCA) remains a clinical challenge that lacks effective therapeutic measures. Here, we show that distinct, stage-wise metabolic alterations in BLCA are associated with the loss of function of aldehyde oxidase (AOX1). AOX1 associated metabolites have a high predictive value for advanced BLCA an...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0902-7

    authors: Vantaku V,Putluri V,Bader DA,Maity S,Ma J,Arnold JM,Rajapakshe K,Donepudi SR,von Rundstedt FC,Devarakonda V,Dubrulle J,Karanam B,McGuire SE,Stossi F,Jain AK,Coarfa C,Cao Q,Sikora AG,Villanueva H,Kavuri SM,Lotan Y

    更新日期:2020-10-01 00:00:00

  • 4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A2 and its receptor.

    abstract::The role of thromboxane A(2) (TxA(2)) in smoking-associated lung cancer is poorly understood. This study was conducted to study the role of TxA(2) in smoking carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-promoted cell survival and growth in human lung cancer cells. We found that NNK increased TxA(2) ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.390

    authors: Huang RY,Li MY,Hsin MK,Underwood MJ,Ma LT,Mok TS,Warner TD,Chen GG

    更新日期:2011-01-06 00:00:00

  • Leukemic cell line, KG-1 has a functional loss of hOGG1 enzyme due to a point mutation and 8-hydroxydeoxyguanosine can kill KG-1.

    abstract::We tested the cytotoxic action of 8-hydroxyguanine (8ohG) by observing the viability of several leukemic cell lines (KG-1, U937, Jurkat and K 562) in the presence of 8-hydroxydeoxyguanosine (8ohdG), a nucleoside of 8ohG. It was found that 8ohdG showed cytotoxic action only to KG-1 and that only KG-1 showed a homozygou...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203787

    authors: Hyun JW,Choi JY,Zeng HH,Lee YS,Kim HS,Yoon SH,Chung MH

    更新日期:2000-09-14 00:00:00