Non-canonical activation of hedgehog in prostate cancer cells mediated by the interaction of transcriptionally active androgen receptor proteins with Gli3.

Abstract:

:Hedgehog (Hh) is an oncogenic signaling pathway that regulates the activity of Gli transcription factors. Canonical Hh is a Smoothened- (Smo-) driven process that alters the post-translational processing of Gli2/Gli3 proteins. Though evidence supports a role for Gli action in prostate cancer (PCa) cell growth and progression, there is little indication that Smo is involved. Here we describe a non-canonical means for activation of Gli transcription in PCa cells mediated by the binding of transcriptionally-active androgen receptors (ARs) to Gli3. Androgens stimulated reporter expression from a Gli-dependent promoter in a variety of AR + PCa cells and this activity was suppressed by an anti-androgen, Enz, or by AR knockdown. Androgens also upregulated expression of endogenous Gli-dependent genes. This activity was associated with increased intranuclear binding of Gli3 to AR that was antagonized by Enz. Fine mapping of the AR binding domain on Gli2 showed that AR recognizes the Gli protein processing domain (PPD) in the C-terminus. Mutations in the arginine-/serine repeat elements of the Gli2 PPD involved in phosphorylation and ubiquitinylation blocked the binding to AR. β-TrCP, a ubiquitin ligase that recognizes the Gli PPD, competed with AR for binding to this site. AR binding to Gli3 suppressed its proteolytic processing to the Gli3 repressor form (Gli3R) whereas AR knockdown increased Gli3R. Both full-length and truncated ARs were able to activate Gli transcription. Finally, we found that an ARbinding decoy polypeptide derived from the Gli2 C-terminus can compete with Gli3 for binding to AR. Exogenous overexpression of this decoy suppressed Gli transcriptional activity in PCa cells. Collectively, this work identifies a novel pathway for non-canonical activation of Hh signaling in PCa cells and identifies a means for interference that may have clinical relevance for PCa patients.

journal_name

Oncogene

journal_title

Oncogene

authors

Li N,Truong S,Nouri M,Moore J,Al Nakouzi N,Lubik AA,Buttyan R

doi

10.1038/s41388-017-0098-7

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

2313-2325

issue

17

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-017-0098-7

journal_volume

37

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • NRARP displays either pro- or anti-tumoral roles in T-cell acute lymphoblastic leukemia depending on Notch and Wnt signaling.

    abstract::T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis in patients with resistant or relapsed disease. Although NOTCH is a known driver in T-ALL, its clinical inhibition has significant limitations. Our previous studies suggested that NRARP, a negative regulator o...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-1042-9

    authors: Pinto I,Duque M,Gonçalves J,Akkapeddi P,Oliveira ML,Cabrita R,Yunes JA,Durum SK,Barata JT,Fragoso R

    更新日期:2020-01-01 00:00:00

  • Cyclin D3 action in androgen receptor regulation and prostate cancer.

    abstract::Prostate cancer (PCa) cell proliferation is dependent on activation of the androgen receptor (AR), a ligand-dependent transcription factor. AR activation controls G1-S phase progression through fostering enhanced translation of the D-type cyclins, which promote cell cycle progression through activation of CDK4/6. Howe...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210981

    authors: Olshavsky NA,Groh EM,Comstock CE,Morey LM,Wang Y,Revelo MP,Burd C,Meller J,Knudsen KE

    更新日期:2008-05-15 00:00:00

  • WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential.

    abstract::We have isolated a gene (WS5) that is specifically expressed at the mRNA and protein level in avian fibroblasts transformed by the v-myc oncogene of avian acute leukemia virus MC29. In a conditional cell transformation system, WS5 gene expression was tightly correlated with v-myc activation. The WS5 gene contains 11 e...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209975

    authors: Reiter F,Hartl M,Karagiannidis AI,Bister K

    更新日期:2007-03-15 00:00:00

  • Males absent on the first (MOF): from flies to humans.

    abstract::Histone modifications such as acetylation, methylation and phosphorylation have been implicated in fundamental cellular processes such as epigenetic regulation of gene expression, organization of chromatin structure, chromosome segregation, DNA replication and DNA repair. Males absent on the first (MOF) is responsible...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1210607

    authors: Rea S,Xouri G,Akhtar A

    更新日期:2007-08-13 00:00:00

  • Twist1 promotes breast cancer invasion and metastasis by silencing Foxa1 expression.

    abstract::The heterogeneous breast cancers can be classified into different subtypes according to their histopathological characteristics and molecular signatures. Foxa1 expression is linked with luminal breast cancer (LBC) with good prognosis, whereas Twist1 expression is associated with basal-like breast cancer (BLBC) with po...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.286

    authors: Xu Y,Qin L,Sun T,Wu H,He T,Yang Z,Mo Q,Liao L,Xu J

    更新日期:2017-02-23 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

  • Analysis of chimeric Gag-Arg/Abl molecules indicates a distinct negative regulatory role for the Arg C-terminal domain.

    abstract::Arg and c-Abl represent the mammalian member of the Abelson family of nonreceptor protein tyrosine kinases. The two proteins are composed of SH2, SH3, kinase and C-terminal domains. To examine Arg structure-function relationships we analysed a Gag-Arg fusion protein, analogous to the oncogenic Gag-Abl fusion protein o...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Mysliwiec T,Perego R,Kruh GD

    更新日期:1996-02-01 00:00:00

  • FYN promotes mesenchymal phenotypes of basal type breast cancer cells through STAT5/NOTCH2 signaling node.

    abstract::Basal type breast cancer is the most aggressive and has mesenchymal features with a high metastatic ability. However, the signaling node that determines the basal type features in breast cancer remains obscure. Here, we report that FYN among SRC family kinases is required for the maintenance of basal type breast cance...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-017-0114-y

    authors: Lee GH,Yoo KC,An Y,Lee HJ,Lee M,Uddin N,Kim MJ,Kim IG,Suh Y,Lee SJ

    更新日期:2018-04-01 00:00:00

  • Distinct conformations of p53 are observed at different stages of keratinocyte differentiation.

    abstract::p53 is a multifunctional protein that has been shown to inhibit the growth of transformed cells, arrest the cell cycle of normal cells, regulate gene transcription and influence cellular differentiation, apoptosis and senescence. This study was undertaken to determine if the expression of p53 in keratinocytes varied d...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Spandau DF

    更新日期:1994-07-01 00:00:00

  • Dependence receptors: a new paradigm in cell signaling and cancer therapy.

    abstract::Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways impl...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2010.13

    authors: Goldschneider D,Mehlen P

    更新日期:2010-04-01 00:00:00

  • Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer.

    abstract::Prostate stem cell antigen (PSCA) is a recently defined homologue of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. PSCA mRNA is expressed in the basal cells of normal prostate and in more than 80% of prostate cancers. The purpose of the present study was to examine PSCA pr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203426

    authors: Gu Z,Thomas G,Yamashiro J,Shintaku IP,Dorey F,Raitano A,Witte ON,Said JW,Loda M,Reiter RE

    更新日期:2000-03-02 00:00:00

  • Ultraviolet light-induced DNA damage triggers apoptosis in nucleotide excision repair-deficient cells via Bcl-2 decline and caspase-3/-8 activation.

    abstract::Ultraviolet (UV) light is a potent mutagenic and genotoxic agent. Whereas DNA damage induced by UV light is known to be responsible for UV-induced genotoxicity, its role in triggering apoptosis is still unclear. We addressed this issue by comparing nucleotide excision repair (NER) deficient 27-1 and 43-3B Chinese hams...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204754

    authors: Dunkern TR,Fritz G,Kaina B

    更新日期:2001-09-20 00:00:00

  • Alu RNA accumulation induces epithelial-to-mesenchymal transition by modulating miR-566 and is associated with cancer progression.

    abstract::Alu sequences are the most abundant short interspersed repeated elements in the human genome. Here we show that in a cell culture model of colorectal cancer (CRC) progression, we observe accumulation of Alu RNA that is associated with reduced DICER1 levels. Alu RNA induces epithelial-to-mesenchymal transition (EMT) by...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.369

    authors: Di Ruocco F,Basso V,Rivoire M,Mehlen P,Ambati J,De Falco S,Tarallo V

    更新日期:2018-02-01 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

  • Reciprocal relationship in gene expression between FGFR1 and FGFR3: implication for tumorigenesis.

    abstract::We have previously demonstrated that the expression of FGFR3 is frequently downregulated in colorectal carcinoma cells. Here we have shown that FGFR1 is overexpressed in colorectal carcinoma cells and the gene expressions between FGFR1 and FGFR3 are mutually exclusive. Moreover, we have also shown that the disruption ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208254

    authors: Jang JH

    更新日期:2005-01-27 00:00:00

  • Beyond the RING: CBL proteins as multivalent adapters.

    abstract::Following discovery of c-Cbl, a cellular form of the transforming retroviral protein v-Cbl, multiple Cbl-related proteins have been identified in vertebrate and invertebrate organisms. c-Cbl and its homologues are capable of interacting with numerous proteins involved in cell signaling, including various molecular ada...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1204781

    authors: Tsygankov AY,Teckchandani AM,Feshchenko EA,Swaminathan G

    更新日期:2001-10-01 00:00:00

  • CXCR7/CXCR4 heterodimer-induced histone demethylation: a new mechanism of colorectal tumorigenesis.

    abstract::Both chemokine receptors (CXCRs) 7 and 4 can facilitate immune cell migration and mediate a vast array of physiological and pathological events. Herein we report, in both human and animal studies, that these two CXCRs can form heterodimers in vivo and promote colorectal tumorigenesis through histone demethylation. Com...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-018-0519-2

    authors: Song ZY,Wang F,Cui SX,Gao ZH,Qu XJ

    更新日期:2019-02-01 00:00:00

  • SPSB3 targets SNAIL for degradation in GSK-3β phosphorylation-dependent manner and regulates metastasis.

    abstract::Epithelial-mesenchymal transition (EMT) is a process during which normal epithelial cells acquire mesenchymal characteristics. EMT has a critical role in various human diseases especially in cancer. EMT facilitates tumor initiation and progression by mediating cancer cell stemness and motility. Zinc finger transcripti...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.370

    authors: Liu Y,Zhou H,Zhu R,Ding F,Li Y,Cao X,Liu Z

    更新日期:2018-02-08 00:00:00

  • Amifostine (WR2721) restores transcriptional activity of specific p53 mutant proteins in a yeast functional assay.

    abstract::Many p53 mutants found in human cancer have an altered ability to bind DNA and transactivate gene expression. Re-expression of functional p53 in cells in which the endogenous TP53 gene is inactivated has been demonstrated to restore a non-tumorigenic phenotype. Pharmacological modulation of p53 mutant conformation may...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204428

    authors: Maurici D,Monti P,Campomenosi P,North S,Frebourg T,Fronza G,Hainaut P

    更新日期:2001-06-14 00:00:00

  • Interferon-α-secreting mesenchymal stem cells exert potent antitumor effect in vivo.

    abstract::Mesenchymal stem cells (MSCs) are a kind of adult stem cells that can be isolated easily from bone marrow, adipose tissue, umbilical cord and many other tissues. MSCs have been shown to specifically migrate to inflammatory sites, including tumors, and hold great promise as tumor-specific vectors to deliver antitumor a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.458

    authors: Xu C,Lin L,Cao G,Chen Q,Shou P,Huang Y,Han Y,Wang Y,Shi Y

    更新日期:2014-10-16 00:00:00

  • The oncofusion protein FUS-ERG targets key hematopoietic regulators and modulates the all-trans retinoic acid signaling pathway in t(16;21) acute myeloid leukemia.

    abstract::The ETS transcription factor ERG has been implicated as a major regulator of both normal and aberrant hematopoiesis. In acute myeloid leukemias harboring t(16;21), ERG function is deregulated due to a fusion with FUS/TLS resulting in the expression of a FUS-ERG oncofusion protein. How this oncofusion protein deregulat...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.261

    authors: Sotoca AM,Prange KH,Reijnders B,Mandoli A,Nguyen LN,Stunnenberg HG,Martens JH

    更新日期:2016-04-14 00:00:00

  • WEE1 accumulation and deregulation of S-phase proteins mediate MLN4924 potent inhibitory effect on Ewing sarcoma cells.

    abstract::Ewing sarcoma (ES) is an aggressive bone and soft tissue tumor of children and young adults in which finding effective new targeted therapies is imperative. Here, we report an in-depth preclinical study of the investigational cullin-RING ubiquitin ligase (CRL) inhibitor MLN4924 in ES, as we have recently demonstrated ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.153

    authors: Mackintosh C,García-Domínguez DJ,Ordóñez JL,Ginel-Picardo A,Smith PG,Sacristán MP,de Álava E

    更新日期:2013-03-14 00:00:00

  • CpG island shore methylation regulates caveolin-1 expression in breast cancer.

    abstract::Caveolin-1 (Cav1) is an integral membrane, scaffolding protein found in plasma membrane invaginations (caveolae). Cav1 regulates multiple cancer-associated processes. In breast cancer, a tumor suppressive role for Cav1 has been suggested; however, Cav1 is frequently overexpressed in aggressive breast cancer subtypes, ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.474

    authors: Rao X,Evans J,Chae H,Pilrose J,Kim S,Yan P,Huang RL,Lai HC,Lin H,Liu Y,Miller D,Rhee JK,Huang YW,Gu F,Gray JW,Huang TM,Nephew KP

    更新日期:2013-09-19 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

  • A role for iron in Wnt signalling.

    abstract::There is an emerging body of evidence implicating iron in carcinogenesis and in particular colorectal cancer, but whether this involves Wnt signalling, a major oncogenic signalling pathway has not been studied. We aimed to determine the effect of iron loading on Wnt signalling using mutant APC (Caco-2 and SW480) and w...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210711

    authors: Brookes MJ,Boult J,Roberts K,Cooper BT,Hotchin NA,Matthews G,Iqbal T,Tselepis C

    更新日期:2008-02-07 00:00:00

  • A CRISPR-based base-editing screen for the functional assessment of BRCA1 variants.

    abstract::Genetic mutations in BRCA1, which is crucial for the process of DNA repair and maintenance of genomic integrity, are known to increase markedly the risk of breast and ovarian cancers. Clinical genetic testing has been used to identify new BRCA1 variants; however, functional assessment and determination of their pathog...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0968-2

    authors: Kweon J,Jang AH,Shin HR,See JE,Lee W,Lee JW,Chang S,Kim K,Kim Y

    更新日期:2020-01-01 00:00:00

  • DNA methylation and gene silencing in cancer: which is the guilty party?

    abstract::The DNA methylation pattern of a cell is exquisitely controlled during early development resulting in distinct methylation patterns. The tight control of DNA methylation is released in the cancer cell characterized by a reversal of methylation states. CpG island associated genes, in particular tumour suppressor or rel...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1205598

    authors: Clark SJ,Melki J

    更新日期:2002-08-12 00:00:00

  • Post-transcriptional processing suggests that c-mos functions as a maternal message in mouse eggs.

    abstract::Transcripts of the c-mos proto-oncogene were recently found to accumulate to high levels in mouse oocytes. We report here that the oocyte c-mos RNA is polyadenylated in concert with oocyte maturation, retained in mature ovulated eggs and zygotes but degraded by the late two cell embryo stage. These results suggest tha...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Goldman DS,Kiessling AA,Cooper GM

    更新日期:1988-08-01 00:00:00

  • Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin.

    abstract::Prostate carcinoma (PCA) is the most frequently diagnosed malignancy in American men. PCA at advanced stages can both proliferate abnormally and resist apoptosis. Among the many known signal transduction pathways, phosphatidylinositide-3'OH kinase (PI3-kinase) has been shown to play an important role in cell survival ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202687

    authors: Xue LY,Qiu Y,He J,Kung HJ,Oleinick NL

    更新日期:1999-06-03 00:00:00

  • Bcr-Abl induces autocrine IGF-1 signaling.

    abstract::Bcr-Abl oncogene is responsible for the initial phase of chronic myelogenous leukemia (CML), which is effectively treated by the Bcr-Abl inhibitor imatinib. Over time patients become resistant to treatment and progress to blast crisis, an event that is driven by additional genetic and epigenetic aberrations. Recently,...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.8

    authors: Lakshmikuttyamma A,Pastural E,Takahashi N,Sawada K,Sheridan DP,DeCoteau JF,Geyer CR

    更新日期:2008-06-19 00:00:00