The Experts below are selected from a list of 4215 Experts worldwide ranked by ideXlab platform
Lurdes Queimado - One of the best experts on this subject based on the ideXlab platform.
-
abstract 4298 microrna 200cmediates the tumor suppressive effects of wnt inhibitory factor 1 in human malignant salivary gland cells
Cancer Research, 2013Co-Authors: Ilangovan Ramachandran, David Obeso, Antonio M C Reis, Sripathi M Sureban, Elangovan Thavathiru, Lurdes QueimadoAbstract:Background: The important role of Wingless-type (Wnt)/β-catenin pathway is well established in various human tumors. Previously, we have demonstrated that Wnt inhibitory factor 1 (WIF1) is significantly downregulated in human salivary gland tumors. The tumor suppressor microRNA, miR-200c, is downregulated in many cancers and is known to repress migration and invasion of cancer cells. Aims: To determine the tumor suppressive effects of WIF1 and delineate the mechanisms by which WIF1 regulates microRNAs in human malignant salivary gland cells. Methods: Human malignant salivary gland cells (Carcinoma ExPleomorphic adenoma, CaExPA79) were transiently transfected with either empty vector or pCI blast-WIF1 and cell proliferation was determined by MTT assay at various time points. CaExPA79 cells transfected with WIF1 for 48 h were used for total RNA isolation and gene expression studies. To determine the effect of WIF1 restoration on salivary gland cancer cells, CaExPA79 cells were treated with 50 μM of 5-aza-2′-deoxycytidine (DAC), a demethylating agent, for 4 days. After DAC treatment, the cells were either used for cell cycle analysis or total RNA isolation and real-time RT-PCR analysis. To determine the effect of WIF1 on miR-200c, CaExPA79 cells were transfected with pCI blast-WIF1 along with miR200c-Luc reporter vector and Renilla luciferase expressing plasmid pRL-TK for 24 h. Luciferase activity was determined using Dual-Luciferase Reporter Assay System. Results: WIF1 significantly inhibited the proliferation of CaExPA79 at 24, 48 and 72 h. Treatment with DAC increased the WIF1 mRNA expression and resulted in a significant accumulation of cells in S phase. DAC treatment also resulted in a significant increase in miR-200c expression. WIF1 over-expression resulted in a significant increase in miR-200c expression and led to a significant reduction in the expression of miR-200c targeted genes as documented by luciferase reporter gene assays. Conclusions: WIF1 inhibits salivary gland cancer cell proliferation and induces cell cycle arrest. Most importantly, our findings suggest that WIF1 is a positive transcriptional regulator of the tumor suppressor microRNA miR-200c and leads to a corresponding downregulation of its downstream targets. Taken together, this study reveals a novel mechanism by which WIF1 elicits it9s tumor suppressive effects on salivary gland cancer cells. Grant support: This work was supported by the Oklahoma Center for the Advancement of Science & Technology (LQ) (HR08-018). LQ holds a Presbyterian Health Foundation Endowed Chair in Otorhinolaryngology. Citation Format: Ilangovan Ramachandran, David Obeso, Sripathi M. Sureban, Elangovan Thavathiru, Antonio Reis, Lurdes Queimado. microRNA-200c mediates the tumor suppressive effects of Wnt inhibitory factor 1 in human malignant salivary gland cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4298. doi:10.1158/1538-7445.AM2013-4298
-
abstract 5625 wnt inhibitory factor 1 is a potent growth inhibitory agent for salivary gland tumor cells
Cancer Research, 2012Co-Authors: Ilangovan Ramachandran, David Obeso, Antonio M Reis, Lurdes QueimadoAbstract:Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background: Aberrant activation of the Wingless-type (Wnt)/β-catenin pathway plays an important role in many human cancers. We have shown that Wnt inhibitory factor 1 (WIF1), a Wnt antagonist, is rearranged in salivary gland pleomorphic adenomas and down-regulated in carcinoma ex-pleomorphic adenomas. Here, we studied the mechanisms of WIF1 down-regulation and also the potential therapeutic implications of WIF1 in human salivary gland tumor cells. Aims: To characterize the mechanisms of WIF1 down-regulation in salivary gland tumor cells and to determine the effects of restoration of WIF1 expression on salivary gland tumor cell growth. Methods: Salivary gland tumor cell lines were treated with the demethylating agent 5-aza-2′-deoxycytidine (50 µM) for 4 days. Then we isolated total RNA and performed real-time RT-PCR to determine WIF1 mRNA expression. To determine the growth suppressive effects of WIF1, salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma cells were stably or transiently transfected with either empty vector or pCI blast-WIF1. The growth inhibitory role of WIF1 was also assessed by exposure of salivary gland tumor cells to pure WIF1 protein. Cell proliferation was assessed at different time points by MTT assay. We performed cell cycle analysis after 72 h of WIF1 transfection by flow cytometry using FACSCalibur analyzer. Results: Treatment with DAC caused about 30-fold and 6-fold increase in WIF1 mRNA expression in salivary gland carcinoma ex-pleomorphic adenoma cells and pleomorphic adenoma cells, respectively compared with vehicle treatment. Stable transfection of salivary gland tumor cells with WIF1 vector induced dramatic nuclear fragmentation and cell death. No viable colonies were observed. Transient transfection with pCI blast-WIF1 or exposure to WIF1 protein significantly decreased the proliferation of salivary gland tumor cells. Cell cycle analysis showed a significant accumulation of cells in G1 phase suggesting that WIF1 re-expression induces G1 arrest in salivary gland tumor cells. Conclusions: Our findings demonstrate that WIF1 is epigenetically silenced by promoter hypermethylation in carcinoma ex-pleomorphic adenoma cells and pleomorphic adenoma cells. Importantly, salivary gland tumor cells stably transfected with WIF1 are non-viable, and exposure to high levels of WIF1 protein resulted in significant growth inhibition. These data show that WIF1 is a potent growth inhibitory agent for salivary gland tumor cells and may serve as a potential therapeutic drug for salivary gland cancer. Grant support: This work was supported by the Oklahoma Center for the Advancement of Science & Technology (LQ) (HR08-018). LQ holds a Presbyterian Health Foundation Endowed Chair in Otorhinolaryngology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5625. doi:1538-7445.AM2012-5625
-
WIF1 an inhibitor of the wnt pathway is rearranged in salivary gland tumors
Genes Chromosomes and Cancer, 2007Co-Authors: Lurdes Queimado, Carla S Lopes, Antonio M C ReisAbstract:Chromosome rearrangements involving 12q13-15 are frequent among several tumors, including pleomorphic adenomas. The common molecular target for these aberrations is the HMGA2 gene, but various fusion partners of HMGA2 have been reported in tumors. Here we report the identification of the WNT inhibitory factor 1 (WIF1) gene as a novel HMGA2 fusion partner in a salivary gland pleomorphic adenoma. In normal salivary gland tissue WIF1 is expressed at a high level and HMGA2 is not expressed. However, in the pleomorphic adenoma expressing the HMGA2/WIF1 fusion transcript, we observed re-expression of HMGA2 wild-type transcripts and very low levels of WIF1 expression. These data suggest a possible synergistic effect between upregulation of HMGA2 and downregulation of WIF1. We screened 13 additional benign and malignant salivary gland tumors and detected WIF1 rearrangement in one out of two carcinomas ex-pleomorphic adenoma analyzed. In this malignant tumor, the rearrangement of one WIF1 allele coexists with loss of the other allele, a classic signature of a tumor suppressor gene. WIF1 is an antagonist of the Wnt signaling pathway, which plays a critical role in human cancer. In transgenic mouse models, Wnt activation leads to a high frequency of benign and malignant salivary gland tumors. To our knowledge, this is the first report suggesting that WIF1 is a recurrent target in human salivary gland oncogenesis and that downregulation of WIF1 plays a role in the development and/or progression of pleomorphic adenomas. © 2006 Wiley-Liss, Inc.
Pilar Carvallo - One of the best experts on this subject based on the ideXlab platform.
-
silencing of tumor suppressor genes rassf1a slit2 and WIF1 by promoter hypermethylation in hereditary breast cancer
Molecular Carcinogenesis, 2013Co-Authors: Carolina Alvarez, Valeria Cornejo, Wanda Fernandez, Mauricio Camus, Teresa Tapia, Alex Munoz, Manuel Alvarez, Luigi Devoto, Pilar CarvalloAbstract:Promoter hypermethylation is gaining strength as one of the main mechanisms through which tumor suppressor genes are silenced during tumor progression. Three tumor suppressor genes are frequently found methylated in their promoter, in concordance with absence of expression, RASSF1A, SLIT2, and WIF1. In addition, a previous array-CGH analysis from our group showed that these genes are found in deleted genomic regions observed in hereditary breast cancer tumors. In the present work we analyzed the methylation status of these three tumor suppressor gene promoters in 47 hereditary breast cancer tumors. Promoter methylation status analysis of hereditary breast tumors revealed high methylation frequencies for the three genes (67% RASSF1A, 80% SLIT2, and 72% WIF1). Additionally, the presence of methylated PCR products was associated with absence of protein expression for the three genes and statistically significant for RASSF1A and WIF1. Interestingly, methylation of all the three genes was found in 4 out of 6 grade I invasive ductal carcinoma tumors. Association between RASSF1A methylation and DCIS tumors was found. These results suggest that silencing of these tumor suppressor genes is an early event in hereditary breast cancer, and could be a marker for pre-malignant phenotypes.
-
abstract 656 promoter hypermethylation and silencing of tumor suppressor genes rassf1a WIF1 slit2 and robo1 in triple negative breast carcinomas
Cancer Research, 2013Co-Authors: Carolina Alvarez, Gloria Garrido, Patricia Gajardo, Alonso Quiroz, Valeria Cornejo, Wanda Fernandez, Mauricio Camus, Pilar CarvalloAbstract:Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Triple negative breast cancers represent 10-17% of all breast carcinomas. They display a high histological grade, a more aggressive clinical behavior and they lack any specific treatment, thus are associated to a bad prognosis. As other cancer types, this cancer is caused by sequential accumulation of mutations and genomic alterations involving tumor suppressor genes and oncogenes. In this matter, inactivation of tumor suppressor genes may occur by deletion, promoter hypermethylation or point mutations. In previous study by array CGH we found several tumor suppressor candidate genes deleted in a hereditary breast cancer set of tumors. In addition we studied 4 of these tumor suppressor genes RASSF1A, WIF1, SLIT2 and ROBO1 in a non triple negative set of breast cancer tumors, and found a high frequency of promoter methylation, statistically associated with loss of protein expression for RASSF1A and WIF1. In the present study we aimed to extend the analysis to triple negative breast cancer tumors due to their clinical relevance. Methylation analysis through MS-PCR revealed that RASSF1A promoter was hypermethylated in 52.9% of triple negative tumors, and presents loss of expression in 80.6% of the tumors. WIF1 promoter was hypermethylated in 89.1% and its protein expression was downregulated in 63.1% of the tumors. For SLIT2 we found frequent promoter hypermethylation among tumors (82.6%) showing loss of expression in 88% of the tumors. MS-PCR analyses were not informative for ROBO1, but protein expression was reduced in 49% of all tumors. Our results show that a high percentage of tumors present silencing of RASSF1A, WIF1, SLIT2 and/or ROBO1, and therefore implying the impairment of the pathways they represent. This findings support these genes may have an important role in triple negative breast tumor development. Fondecyt 1080595. Citation Format: Carolina Alvarez, Gloria Garrido, Patricia Gajardo, Alonso Quiroz, Valeria Cornejo, Wanda Fernandez, Mauricio Camus, Pilar Carvallo. Promoter hypermethylation and silencing of tumor suppressor genes RASSF1A, WIF1, SLIT2 and ROBO1 in triple negative breast carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 656. doi:10.1158/1538-7445.AM2013-656
Antonio M C Reis - One of the best experts on this subject based on the ideXlab platform.
-
abstract 4298 microrna 200cmediates the tumor suppressive effects of wnt inhibitory factor 1 in human malignant salivary gland cells
Cancer Research, 2013Co-Authors: Ilangovan Ramachandran, David Obeso, Antonio M C Reis, Sripathi M Sureban, Elangovan Thavathiru, Lurdes QueimadoAbstract:Background: The important role of Wingless-type (Wnt)/β-catenin pathway is well established in various human tumors. Previously, we have demonstrated that Wnt inhibitory factor 1 (WIF1) is significantly downregulated in human salivary gland tumors. The tumor suppressor microRNA, miR-200c, is downregulated in many cancers and is known to repress migration and invasion of cancer cells. Aims: To determine the tumor suppressive effects of WIF1 and delineate the mechanisms by which WIF1 regulates microRNAs in human malignant salivary gland cells. Methods: Human malignant salivary gland cells (Carcinoma ExPleomorphic adenoma, CaExPA79) were transiently transfected with either empty vector or pCI blast-WIF1 and cell proliferation was determined by MTT assay at various time points. CaExPA79 cells transfected with WIF1 for 48 h were used for total RNA isolation and gene expression studies. To determine the effect of WIF1 restoration on salivary gland cancer cells, CaExPA79 cells were treated with 50 μM of 5-aza-2′-deoxycytidine (DAC), a demethylating agent, for 4 days. After DAC treatment, the cells were either used for cell cycle analysis or total RNA isolation and real-time RT-PCR analysis. To determine the effect of WIF1 on miR-200c, CaExPA79 cells were transfected with pCI blast-WIF1 along with miR200c-Luc reporter vector and Renilla luciferase expressing plasmid pRL-TK for 24 h. Luciferase activity was determined using Dual-Luciferase Reporter Assay System. Results: WIF1 significantly inhibited the proliferation of CaExPA79 at 24, 48 and 72 h. Treatment with DAC increased the WIF1 mRNA expression and resulted in a significant accumulation of cells in S phase. DAC treatment also resulted in a significant increase in miR-200c expression. WIF1 over-expression resulted in a significant increase in miR-200c expression and led to a significant reduction in the expression of miR-200c targeted genes as documented by luciferase reporter gene assays. Conclusions: WIF1 inhibits salivary gland cancer cell proliferation and induces cell cycle arrest. Most importantly, our findings suggest that WIF1 is a positive transcriptional regulator of the tumor suppressor microRNA miR-200c and leads to a corresponding downregulation of its downstream targets. Taken together, this study reveals a novel mechanism by which WIF1 elicits it9s tumor suppressive effects on salivary gland cancer cells. Grant support: This work was supported by the Oklahoma Center for the Advancement of Science & Technology (LQ) (HR08-018). LQ holds a Presbyterian Health Foundation Endowed Chair in Otorhinolaryngology. Citation Format: Ilangovan Ramachandran, David Obeso, Sripathi M. Sureban, Elangovan Thavathiru, Antonio Reis, Lurdes Queimado. microRNA-200c mediates the tumor suppressive effects of Wnt inhibitory factor 1 in human malignant salivary gland cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4298. doi:10.1158/1538-7445.AM2013-4298
-
WIF1 an inhibitor of the wnt pathway is rearranged in salivary gland tumors
Genes Chromosomes and Cancer, 2007Co-Authors: Lurdes Queimado, Carla S Lopes, Antonio M C ReisAbstract:Chromosome rearrangements involving 12q13-15 are frequent among several tumors, including pleomorphic adenomas. The common molecular target for these aberrations is the HMGA2 gene, but various fusion partners of HMGA2 have been reported in tumors. Here we report the identification of the WNT inhibitory factor 1 (WIF1) gene as a novel HMGA2 fusion partner in a salivary gland pleomorphic adenoma. In normal salivary gland tissue WIF1 is expressed at a high level and HMGA2 is not expressed. However, in the pleomorphic adenoma expressing the HMGA2/WIF1 fusion transcript, we observed re-expression of HMGA2 wild-type transcripts and very low levels of WIF1 expression. These data suggest a possible synergistic effect between upregulation of HMGA2 and downregulation of WIF1. We screened 13 additional benign and malignant salivary gland tumors and detected WIF1 rearrangement in one out of two carcinomas ex-pleomorphic adenoma analyzed. In this malignant tumor, the rearrangement of one WIF1 allele coexists with loss of the other allele, a classic signature of a tumor suppressor gene. WIF1 is an antagonist of the Wnt signaling pathway, which plays a critical role in human cancer. In transgenic mouse models, Wnt activation leads to a high frequency of benign and malignant salivary gland tumors. To our knowledge, this is the first report suggesting that WIF1 is a recurrent target in human salivary gland oncogenesis and that downregulation of WIF1 plays a role in the development and/or progression of pleomorphic adenomas. © 2006 Wiley-Liss, Inc.
David Shore - One of the best experts on this subject based on the ideXlab platform.
-
Rif1 Binding and Control of Chromosome-Internal DNA Replication Origins Is Limited by Telomere Sequestration.
Cell reports, 2018Co-Authors: Lukas Hafner, Aleksandra Lezaja, Xu Zhang, Laure Lemmens, Maksym Shyian, Benjamin Albert, Cindy Follonier, Jose Manuel Nunes, Massimo Lopes, David ShoreAbstract:The Saccharomyces cerevisiae telomere-binding protein Rif1 plays an evolutionarily conserved role in control of DNA replication timing by promoting PP1-dependent dephosphorylation of replication initiation factors. However, ScRif1 binding outside of telomeres has never been detected, and it has thus been unclear whether Rif1 acts directly on the replication origins that it controls. Here, we show that, in unperturbed yeast cells, Rif1 primarily regulates late-replicating origins within 100 kb of a telomere. Using the chromatin endogenous cleavage ChEC-seq technique, we robustly detect Rif1 at late-replicating origins that we show are targets of its inhibitory action. Interestingly, abrogation of Rif1 telomere association by mutation of its Rap1-binding module increases Rif1 binding and origin inhibition elsewhere in the genome. Our results indicate that Rif1 inhibits replication initiation by interacting directly with origins and suggest that Rap1-dependent sequestration of Rif1 increases its effective concentration near telomeres, while limiting its action at chromosome-internal sites.
-
Rif1 Binding and Control of Chromosome-Internal DNA Replication Origins Is Limited by Telomere Sequestration
Elsevier, 2018Co-Authors: Lukas Hafner, Aleksandra Lezaja, Xu Zhang, Laure Lemmens, Maksym Shyian, Benjamin Albert, Cindy Follonier, Jose Manuel Nunes, Massimo Lopes, David ShoreAbstract:Summary: The Saccharomyces cerevisiae telomere-binding protein Rif1 plays an evolutionarily conserved role in control of DNA replication timing by promoting PP1-dependent dephosphorylation of replication initiation factors. However, ScRif1 binding outside of telomeres has never been detected, and it has thus been unclear whether Rif1 acts directly on the replication origins that it controls. Here, we show that, in unperturbed yeast cells, Rif1 primarily regulates late-replicating origins within 100 kb of a telomere. Using the chromatin endogenous cleavage ChEC-seq technique, we robustly detect Rif1 at late-replicating origins that we show are targets of its inhibitory action. Interestingly, abrogation of Rif1 telomere association by mutation of its Rap1-binding module increases Rif1 binding and origin inhibition elsewhere in the genome. Our results indicate that Rif1 inhibits replication initiation by interacting directly with origins and suggest that Rap1-dependent sequestration of Rif1 increases its effective concentration near telomeres, while limiting its action at chromosome-internal sites. : Hafner et al. use cell-sorting assays and chromatin endogenous cleavage sequencing (ChEC-seq) to characterize the repressive effect of Rif1 protein on DNA replication initiation. They find that global replication dynamics are controlled by telomeric sequestration of Rif1 by the telomere repeat binding protein Rap1. Keywords: chromatin endogenous cleavage, ChEC, DNA replication origins, DNA replication timing, Rap1, Rif1, Saccharomyces cerevisia
Irene Vassallo - One of the best experts on this subject based on the ideXlab platform.
-
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity
2016Co-Authors: Gene Section, Atlas Of Genetics, Wif Inhibitory Factor, Irene Vassallo, Monika E HegiAbstract:The human WIF1 gene is located on the chromosome 12q14.2 from 65444404 bp to 65515346 bp (from pter). It is oriented on the minus strand and comprises 10 exons spanning 71007 bp of genomic DNA. The first and the 10th exons are partially composed by untranslated regions. Transcription The mRNA produced is 2304 bp long. The promoter region of WIF1 has been cloned and studied by Reguart et al. and its structure is shown in Figure 2B (Reguart et al., 2004). Regulatory elements in the WIF1 promoter comprise a TATA box and binding sites of the transcription factors: Engrailed, E2F, GLI-Kruppel, NF-κB, and MYC, as visualized in Figure 2B. The CpG island located upstream of the WIF1 transcriptional start site is prone to aberrant methylation in various tumor types. Hypermethylation of this region has been found to be responsible for WIF1 downregulation, suggestive of tumor suppressor properties in different cancer types
-
abstract 585 WIF1 re expression in glioblastoma impairs migration through downregulation of the lncrna malat1
Cancer Research, 2014Co-Authors: Irene Vassallo, Mariefrance Hamou, Monika E HegiAbstract:Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Glioblastoma is the most aggressive form of human glioma. Despite progress in brain tumor therapy the prognosis remains dismal with a median survival of 15 months. We have recently shown that WIF1, an inhibitor of the WNT pathway, is downregulated in glioblastoma where it functions as strong tumor suppressor gene. Indeed, WIF1 re-expression impairs cell growth, cell migration, induces a senescence-like phenotype, and inhibits tumorigenicity in several orthotopic xenograft models. To analyse the molecular mechanisms underlying the tumor suppressive functions of WIF1 we developed a TET-on inducible system. Gene expression profiling following WIF1 induction revealed several interesting candidate genes validated in additional cell lines. The gene with strongest downregulation in WIF1-induced cells was MALAT1. MALAT1 is a long non-coding RNA that has been associated with tumor aggressiveness and invasion. Hence, MALAT1 is a plausible candidate, and its downregulation may contribute to the attenuation of malignancy seen in WIF1 expressing cells. Preliminary results show that the expression of a MALAT1 specific short-hairpin drastically reduces the infiltrative capability of glioblastoma cells. Analysis of gene xpression profiles revealed that MALAT1 is overexpressed in glioblastoma as compared to non-tumoral brain. These observations suggest that MALAT1 may contribute to the aggressive phenotype of glioblastoma. Experiments to test the effect of downregulation of MALAT1 in vivo are now ongoing. The poor prognosis is partially due to the extremely high capability of glioblastoma cells to migrate and to invade the surrounding brain structures, impairing complete surgical resection, hence leading inevitably to recurrence. This provides the rational to further investigate implications of MALAT1 in migration. Understanding the mechanisms of high invasive properties may indeed lead to the identification of new targets for therapy. Citation Format: Irene Vassallo, Marie-France Hamou, Monika E. Hegi. WIF1 re-expression in glioblastoma impairs migration through downregulation of the lncRNA MALAT1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 585. doi:10.1158/1538-7445.AM2014-585
-
neurochemical profile differentiation of glioma induced by cancer stem cells expressing WIF1 a 1h mrs longitudinal study at 14 1t
International Society for Magnetic Resonance in Medicine, 2014Co-Authors: Marta Lai, Irene Vassallo, Monika E Hegi, Mariefrance Hamou, Cristina Cudalbu, Bernard Lanz, Rolf GruetterAbstract:Keywords: 1H MRS ; cancer stem cells ; WIF1 ; CIBM-AIT Reference EPFL-CONF-203435 Record created on 2014-11-18, modified on 2017-05-12
-
WIF1 wnt inhibitory factor 1
Atlas of genetics and cytogenetics in oncology and haematology, 2012Co-Authors: Irene Vassallo, M E HegiAbstract:Review on WIF1 (WNT inhibitory factor 1), with data on DNA, on the protein encoded, and where the gene is implicated.
-
the wnt inhibitory factor 1 WIF1 is targeted in glioblastoma and has a tumor suppressing function potentially by induction of senescence
Neuro-oncology, 2011Co-Authors: Wanyu L Lambiv, Irene Vassallo, Mauro Delorenzi, Tal Shay, Annieclaire Diserens, Anjan Misra, Burt G Feuerstein, Anastasia Murat, Eugenia Migliavacca, Mariefrance HamouAbstract:Gene expression-based prediction of genomic copy number aberrations in the chromosomal region 12q13 to 12q15 that is flanked by MDM2 and CDK4 identified Wnt inhibitory factor 1 (WIF1) as a candidate tumor suppressor gene in glioblastoma. WIF1 encodes a secreted Wnt antagonist and was strongly downregulated in most glioblastomas as compared with normal brain, implying deregulation of Wnt signaling, which is associated with cancer. WIF1 silencing was mediated by deletion (7/69, 10%) or epigenetic silencing by promoter hypermethylation (29/110, 26%). Co-amplification of MDM2 and CDK4 that is present in 10% of glioblastomas was associated in most cases with deletion of the whole genomic region enclosed, including the WIF1 locus. This interesting pathogenetic constellation targets the RB and p53 tumor suppressor pathways in tandem, while simultaneously activating oncogenic Wnt signaling.