Antagonistic Regulation of Apoptosis and Differentiation by the Cut Transcription Factor Represents a Tumor-Suppressing Mechanism in Drosophila
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{"title"=>"Antagonistic regulation of apoptosis and differentiation by the cut transcription factor represents a tumor-suppressing mechanism in drosophila", "type"=>"journal", "authors"=>[{"first_name"=>"Zongzhao", "last_name"=>"Zhai", "scopus_author_id"=>"35760776700"}, {"first_name"=>"Nati", "last_name"=>"Ha", "scopus_author_id"=>"55164138600"}, {"first_name"=>"Fani", "last_name"=>"Papagiannouli", "scopus_author_id"=>"6503978429"}, {"first_name"=>"Anne", "last_name"=>"Hamacher-Brady", "scopus_author_id"=>"14028289100"}, {"first_name"=>"Nathan", "last_name"=>"Brady", "scopus_author_id"=>"14027840000"}, {"first_name"=>"Sebastian", "last_name"=>"Sorge", "scopus_author_id"=>"55162660500"}, {"first_name"=>"Daniela", "last_name"=>"Bezdan", "scopus_author_id"=>"15845248400"}, {"first_name"=>"Ingrid", "last_name"=>"Lohmann", "scopus_author_id"=>"6505988235"}], "year"=>2012, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "scopus"=>"2-s2.0-84859226498", "sgr"=>"84859226498", "pui"=>"364556465", "pmid"=>"22438831", "doi"=>"10.1371/journal.pgen.1002582"}, "id"=>"69047a40-3719-337d-bcf3-19e6cba1db85", "abstract"=>"Apoptosis is essential to prevent oncogenic transformation by triggering self-destruction of harmful cells, including those unable to differentiate. However, the mechanisms linking impaired cell differentiation and apoptosis during development and disease are not well understood. Here we report that the Drosophila transcription factor Cut coordinately controls differentiation and repression of apoptosis via direct regulation of the pro-apoptotic gene reaper. We also demonstrate that this regulatory circuit acts in diverse cell lineages to remove uncommitted precursor cells in status nascendi and thereby interferes with their potential to develop into cancer cells. Consistent with the role of Cut homologues in controlling cell death in vertebrates, we find repression of apoptosis regulators by Cux1 in human cancer cells. Finally, we present evidence that suggests that other lineage-restricted specification factors employ a similar mechanism to put the brakes on the oncogenic process.", "link"=>"http://www.mendeley.com/research/antagonistic-regulation-apoptosis-differentiation-cut-transcription-factor-represents-tumorsuppressi", "reader_count"=>43, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>4, "Researcher"=>9, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>7, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>4, "Researcher"=>9, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>7, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>11, "Agricultural and Biological Sciences"=>30, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>30}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>11}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>2, "France"=>1, "Portugal"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/667725"], "description"=>"<p>(A, E, I) Scanning electron micrographs of individual ommatidia of adult <i>Drosophila</i> fly eyes with indicated genotypes are shown. The closed, red arrowheads in (A) mark interommatidial bristles, the open, red arrowheads in (E) mark the absence of these structures. The closed, light red arrowheads in (I) indicate the presence of tissue that would normally develop into interommatidial bristles. (B, F, J) Projections of consecutive confocal sections of one ommatidium of 50 h pupal retinas labeled with DE-Cadherin. Interommatidial bristles are marked by red, closed arrowheads in (B). Open arrowheads in (F) mark absence of DE-Cad, light-red arrowheads in (J) mark reduced DE-Cadherin levels in shaft cells of interommatidial bristles. (C, G) Projections of consecutive confocal sections of one ommatidium of 50 h pupal retinas of <i>GMR::lacZ</i> control (C) and <i>GMR::ct<sup>RNAi</sup></i> flies (G). (D, H) Expression of the apoptosis marker Caspase-3 (Casp-3) in 3<sup>rd</sup> instar eye-antennal discs of control <i>Dcr2; ey::lacZ</i> (D) and <i>Dcr2; ey::2xct<sup>RNAi</sup></i> (H) animals. Yellow asterisks in (H) mark Casp-3 positive cells in <i>Dcr2; ey::2xct<sup>RNAi</sup></i> eye imaginal discs. (K) Relative mRNA expression levels of <i>rpr</i>, <i>grim</i>, <i>Wrinkled</i> (<i>W</i>) and <i>sickle</i> (<i>skl</i>) in 3<sup>rd</sup> instar eye-antennal discs of control <i>Dcr2; ey::lacZ</i> and <i>Dcr2; ey::2xct<sup>RNAi</sup></i> animals.</p>", "links"=>[], "tags"=>["ct", "apoptosis", "repression", "induction"], "article_id"=>338208, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Zongzhao Zhai", "Nati Ha", "Fani Papagiannouli", "Anne Hamacher-Brady", "Nathan Brady", "Sebastian Sorge", "Daniela Bezdan", "Ingrid Lohmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002582.g003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_General_function_of_Ct_in_apoptosis_repression_and_induction_of_differentiation_/338208", "title"=>"General function of Ct in apoptosis repression and induction of differentiation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:16:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/668076"], "description"=>"<p>(A) Relative mRNA expression of eight apoptosis genes after lenti-virus transduced stable Cux1 (p200) knock-down in human Panc1 cancer cells. RT-PCRs are shown for two independent Cux1 knock-down lines, KDa in blue and KDb in red. Results are shown as the expression ratios between shCux1/shC-treated cells and are representative for three independent experiments. Western blot shows knock-down efficiencies in both independent stable Cux1 (p200) knock-down lines (KDa, KDb) and Cux1 expression in an shRNA control knock-down. Stronger effects of KDa (reduced) versus KDb (almost complete) p200 Cux1 knock-down on target gene expression is very likely due to the processed p110 Cux1 isoform, which can have opposite transcriptional effects to the p200 full-length form <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002582#pgen.1002582-Stratigopoulos1\" target=\"_blank\">[62]</a>. (B, C) Distribution of average conservation (B) and average number of conserved DNA binding motifs per 1000 bp (C) in all non-coding regions of the <i>D. melanogaster</i> genome. The red bars highlight the <i>rpr</i> intergenic regions, showing that 93% of all <i>D. melanogaster</i> non-coding regions are less conserved (B) and 89% of all non-coding regions have fewer conserved DNA binding sites per 1000 bp (C) compared to the <i>rpr</i> intergenic regions. (D) Conservation graph of the sequence located downstream of the <i>rpr</i> coding region obtained from the UCSC genome browser (<a href=\"http://genome.ucsc.edu/\" target=\"_blank\">http://genome.ucsc.edu/</a>). The following regulatory regions tested are marked in different colors: <i>rpr</i>-HRE-571 (light-red), <i>rpr</i>-HRE-571+210 (dark-red), <i>rpr</i>-HRE-707 (light-blue) and <i>rpr</i>-HRE-707+156 (dark-blue). (E–H) Reporter gene expression driven by the fragments described above. The <i>rpr</i>-HRE-571 enhancer drives reporter gene expression in the PS (E), which is abolished in the <i>rpr</i>-HRE-571+210 reporter line (G). Similarly, reporter gene expression in CNS midline cells in the <i>rpr</i>-HRE-707 line (F) is completely suppressed in the <i>rpr</i>-HRE-707+156 transgenic line (H). Closed, yellow arrowheads in (E) and (F) mark presence of reporter gene expression, whereas open, yellow arrowheads in (G) and (H) mark absence of GFP expression. (I, J) Co-localization of GFP with Sal in the <i>rpr</i>-HRE-571 (I) and with Vvl in the <i>rpr</i>-HRE-707 (J) reporter lines. (K) Quantification of primary and secondary tumor formation in different genetic backgrounds. Only when Vvl function is reduced and apoptosis is simultaneously inhibited, tumors and metastasis develop. (L, M) <i>rpr</i> transcripts are not found in CNS midline cells of stage 14 wild-type embryos (L) but in <i>vvl</i> mutants (M).</p>", "links"=>[], "tags"=>["evolutionary", "coupling", "differentiation", "apoptosis", "transcription"], "article_id"=>338555, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Zongzhao Zhai", "Nati Ha", "Fani Papagiannouli", "Anne Hamacher-Brady", "Nathan Brady", "Sebastian Sorge", "Daniela Bezdan", "Ingrid Lohmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002582.g006", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_and_evolutionary_conservation_of_coupling_differentiation_and_apoptosis_on_the_transcription_factor_level_/338555", "title"=>"Functional and evolutionary conservation of coupling differentiation and apoptosis on the transcription factor level.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:22:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/667836"], "description"=>"<p>(A–M) Adult compound eyes of the respective genotypes are shown. (L) <i>eyeful::ct<sup>RNAi</sup>; p35</i> flies show high frequency of long range metastasis (marked by yellow arrowhead), a close-up of which is shown in (M). Eyes of such <i>eyeful::ct<sup>RNAi</sup>; p35</i> flies show undifferentiated and overproliferated eye tissue (marked by light blue arrowhead). (N) Quantification of primary and secondary tumor formation in different genetic backgrounds. (O) Relative transcript levels of selected genes involved in cell cycle control, DNA damage response, growth control and epigenetic regulation in eye-antennal discs of 3<sup>rd</sup> instar larvae of pre-oncogenic control animals (<i>ey::Dl</i>) and animals with reduced Ct activity (<i>ey::Dl;2xct<sup>RNAi</sup></i>). (P) Expression of the apoptosis marker Caspase-3 (Casp-3) and the proliferation marker Phosphorylated histone H3 (PH3) in representative 3<sup>rd</sup> instar eye-antennal discs of <i>ey::Dl</i> and <i>ey::Dl;2xct<sup>RNAi</sup></i> animals. An increase in Casp-3 and PH3 positive cells is seen in the area below the dashed, yellow line highlighting the morphogenetic furrow. (Q) Top panel: representative pictures of eyes from <i>ey::Dl;PI3K<sup>RNAi</sup></i> and <i>ey::Dl;2xct<sup>RNAi</sup>;PI3K<sup>RNAi</sup></i> animals. Bottom panel: quantification of tumorous eye growth, secondary tumor growth and “small eye” phenotype in <i>ey::Dl;2xct<sup>RNAi</sup></i> and <i>ey::Dl;2xct<sup>RNAi</sup>;PI3K<sup>RNAi</sup></i> and <i>ey::Dl;PI3K<sup>RNAi</sup></i> animals.</p>", "links"=>[], "tags"=>["ct", "represents", "cancer"], "article_id"=>338321, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Zongzhao Zhai", "Nati Ha", "Fani Papagiannouli", "Anne Hamacher-Brady", "Nathan Brady", "Sebastian Sorge", "Daniela Bezdan", "Ingrid Lohmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002582.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Ct_switch_function_represents_a_cancer_prevention_mechanism_/338321", "title"=>"The Ct switch function represents a cancer prevention mechanism.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:18:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/342038", "https://ndownloader.figshare.com/files/342080", "https://ndownloader.figshare.com/files/342126", "https://ndownloader.figshare.com/files/342167", "https://ndownloader.figshare.com/files/342239", "https://ndownloader.figshare.com/files/342275", "https://ndownloader.figshare.com/files/342330", "https://ndownloader.figshare.com/files/342363", "https://ndownloader.figshare.com/files/342400"], "description"=>"<div><p>Apoptosis is essential to prevent oncogenic transformation by triggering self-destruction of harmful cells, including those unable to differentiate. However, the mechanisms linking impaired cell differentiation and apoptosis during development and disease are not well understood. Here we report that the <em>Drosophila</em> transcription factor Cut coordinately controls differentiation and repression of apoptosis via direct regulation of the pro-apoptotic gene <em>reaper</em>. We also demonstrate that this regulatory circuit acts in diverse cell lineages to remove uncommitted precursor cells <em>in status nascendi</em> and thereby interferes with their potential to develop into cancer cells. Consistent with the role of Cut homologues in controlling cell death in vertebrates, we find repression of apoptosis regulators by Cux1 in human cancer cells. Finally, we present evidence that suggests that other lineage-restricted specification factors employ a similar mechanism to put the brakes on the oncogenic process.</p> </div>", "links"=>[], "tags"=>["antagonistic", "apoptosis", "differentiation", "transcription", "represents", "tumor-suppressing"], "article_id"=>127613, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Zongzhao Zhai", "Nati Ha", "Fani Papagiannouli", "Anne Hamacher-Brady", "Nathan Brady", "Sebastian Sorge", "Daniela Bezdan", "Ingrid Lohmann"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002582.s001", "https://dx.doi.org/10.1371/journal.pgen.1002582.s002", "https://dx.doi.org/10.1371/journal.pgen.1002582.s003", "https://dx.doi.org/10.1371/journal.pgen.1002582.s004", "https://dx.doi.org/10.1371/journal.pgen.1002582.s005", "https://dx.doi.org/10.1371/journal.pgen.1002582.s006", "https://dx.doi.org/10.1371/journal.pgen.1002582.s007", "https://dx.doi.org/10.1371/journal.pgen.1002582.s008", "https://dx.doi.org/10.1371/journal.pgen.1002582.s009"], "stats"=>{"downloads"=>6, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Antagonistic_Regulation_of_Apoptosis_and_Differentiation_by_the_Cut_Transcription_Factor_Represents_a_Tumor_Suppressing_Mechanism_in_Drosophila_/127613", "title"=>"Antagonistic Regulation of Apoptosis and Differentiation by the Cut Transcription Factor Represents a Tumor-Suppressing Mechanism in <em>Drosophila</em>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-03-15 02:06:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/668192"], "description"=>"<p>(A) During normal development, cell-type specification factors like Cut ensure the survival of cells by repressing apoptosis while at the same time these factors also induce a specific differentiation program, which generates cells with a specific terminal cell fate. (B) In the case of a mutation in a cell-type specification factor those cells unable to differentiate, which are potentially harmful to the organism, are removed by releasing apoptosis repression conferred by the same cell-type specification factor. Thus, the transcriptional coupling of differentiation and apoptosis regulation represents a very fast and efficient cancer prevention mechanism. (C) Together with other mutations creating a sensitized background, like the over-activation of the Notch (N) signaling pathway, cells that acquire the inability to differentiate and a resistance to apoptosis activation, two important hallmarks of cancer <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002582#pgen.1002582-Hanahan1\" target=\"_blank\">[1]</a>, <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002582#pgen.1002582-Harris1\" target=\"_blank\">[2]</a>, very easily develop into cancer cells.</p>", "links"=>[], "tags"=>["cancer", "specifying", "transcription", "factors"], "article_id"=>338670, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Zongzhao Zhai", "Nati Ha", "Fani Papagiannouli", "Anne Hamacher-Brady", "Nathan Brady", "Sebastian Sorge", "Daniela Bezdan", "Ingrid Lohmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002582.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_of_cancer_prevention_mechanism_by_cell_fate_specifying_transcription_factors_like_Cut_/338670", "title"=>"Model of cancer prevention mechanism by cell fate specifying transcription factors like Cut.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:24:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/667570"], "description"=>"<p>(A–E) Cuticle preparations of the different genotypes with focus on the PS of 1<sup>st</sup> instar <i>Drosophila</i> larvae. Closed, orange arrowheads in (A) and (B) mark the filzkörper, whereas open, orange arrowheads in (C, D and E) indicate the absence of this structure in the respective genotypes. (F–L) Labeling of the different parts of the PS primordium of stage 15 embryos in the different genetic backgrounds using the filzkörper marker Ct (red, nuclear), the stigmatophore marker Sal (blue) and the apical membrane marker Crb (red). In (G, I, J, K and L) GFP expression (green) driven by the <i>ems</i>-GAL4 driver is shown in the different genetic backgrounds. Red asterisks in (F′–J′) mark the invaginated cells of the future filzkörper. Closed, yellow circles in (F) and (G) mark Ct-positive, invaginated filzkörper precursor cells, dashed yellow circle in (H) indicates the absence of these cells. Dashed, light blue circle in (I) highlights the absence of GFP-positive cells, whereas closed, light blue circle in (J) mark the presence of these cells. Note that some cells expressing <i>GFP</i> under the control of the <i>ems</i>-GAL4 driver invaginate deeper than the Ct expressing cells, thus they are still present in <i>ct<sup>db7</sup></i> mutant embryos, indicated by closed, green arrowheads in (K) and (L). Closed, yellow arrowhead in (K) marks Ct and GFP-positive cells in <i>ems</i>::<i>GFP</i> embryos. Open, yellow arrowhead in (L) highlights the absence of these cells in <i>ct</i> mutant embryos. In (A) to (J′) lateral views, in (K) and (L) dorsal views of embryos are shown.</p>", "links"=>[], "tags"=>["repression", "apoptosis"], "article_id"=>338059, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Zongzhao Zhai", "Nati Ha", "Fani Papagiannouli", "Anne Hamacher-Brady", "Nathan Brady", "Sebastian Sorge", "Daniela Bezdan", "Ingrid Lohmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002582.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cut_dependent_repression_of_apoptosis_is_required_for_cell_survival_and_differentiation_/338059", "title"=>"Cut-dependent repression of apoptosis is required for cell survival and differentiation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:14:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/667399"], "description"=>"<p>(A) Posterior spiracle (PS) of a 1<sup>st</sup> instar wild-type <i>Drosophila</i> larva. The filzkörper is highlighted by red asterisks. (B, C) <i>rpr</i> mRNA (green) expression in stage 11 wild-type (B) and <i>ct</i> mutant (C) embryos. Spalt (Sal) protein (blue) labels stigmatophore precursor cells, Cut (Ct) protein (red, nuclear) marks spiracular chamber and filzkörper precursor cells and the apical membrane marker Crb (red) outlines the cells. Small, green arrows in (C) mark <i>rpr</i> positive spiracular chamber and filzkörper precursor cells in the eighth abdominal segment (A8) of <i>ct</i> mutant embryos. (D, E) Over-expression of the apoptosis sensor UAS-<i>Apoliner</i> using the <i>arm</i>-GAL4 driver in stage 11 wild-type (D) and <i>ct</i> mutant (E) embryos. Small, green arrows in (E) mark apoptotic cells in PS precursor cells (A8) of <i>ct</i> mutant embryos. (F, G) TUNEL stainings in wild-type (F) and <i>ct</i> mutant (G) embryos. Closed arrowhead in (G) marks TUNEL-positive cells in <i>ct</i> mutants, which are absent in wild-type embryos (F). (H, I) Co-localization of GFP protein and <i>rpr</i> mRNA (H) or Cut protein (I) in stage 15 <i>rpr</i>-HRE-571 embryos. White circles mark the PS primordium. (J) Top: conservation blot of <i>rpr</i>-HRE-571 genomic region obtained from the UCSC genome browser (<a href=\"http://genome.ucsc.edu/\" target=\"_blank\">http://genome.ucsc.edu/</a>). Species used for generating blot are also shown in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002582#pgen.1002582.s002\" target=\"_blank\">Figure S2A</a>. Bottom: diagram of the <i>rpr</i>-HRE-571 deletion constructs tested. (K) EMSA using S2 sub-fragment with Ct binding sites either in wild-type (wt probe) or mutated (mut. probe) version and no protein (−), purified MBP protein (M), and purified Cut-MBP fusion protein consisting of the Cut repeat 3 and the Cut homeodomain (C). The black arrowheads indicate the specific DNA-protein complexes. Loading of equal amounts of labeled wild-type and mutated oligonucleotides is illustrated by formation of comparable amounts of unspecific DNA-protein complexes (black arrow). (L–O) Reporter gene expression in the PS of stage 15 embryos driven by the fragments described above. In the S2-Ctbs-GFP, line Ct binding sites within the <i>rpr</i>-HRE-571-S2 fragment are mutated. Spalt (Sal) and Cut (Ct) proteins label stigmatophore (blue) or spiracular chamber and filzkörper cells (red). Closed, yellow arrowheads in (N) and (M) mark reporter gene expression in filzkörper cells, whereas open, yellow arrowheads in (L) and (M) mark missing GFP expression.</p>", "links"=>[], "tags"=>["represses", "apoptosis", "ps"], "article_id"=>337880, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Zongzhao Zhai", "Nati Ha", "Fani Papagiannouli", "Anne Hamacher-Brady", "Nathan Brady", "Sebastian Sorge", "Daniela Bezdan", "Ingrid Lohmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002582.g001", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cut_directly_represses_rpr_and_apoptosis_in_the_PS_primordium_/337880", "title"=>"Cut directly represses <i>rpr</i> and apoptosis in the PS primordium.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:11:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/667962"], "description"=>"<p>(A) Changes in expression of cell adhesion genes in 3<sup>rd</sup> instar eye-antennal imaginal discs of <i>ey</i>::<i>Dl</i>;<i>2xct<sup>RNAi</sup></i> versus <i>ey</i>::<i>Dl</i> animals identified by expression profiling experiments. Red arrows indicate reduced expression, green arrow induced expression of the respective genes in <i>ey</i>::<i>Dl</i>;<i>2xct<sup>RNAi</sup></i> animals. (B) Top: Representative pictures of tumor growth in <i>ey</i>::<i>Dl</i>;<i>βPSintegrin<sup>RNAi</sup></i> and <i>ey</i>::<i>Dl</i>;<i>αPS4integrin<sup>RNAi</sup></i> flies. Green arrowhead marks secondary tumor growth in the abdomen. Bottom: Quantification of primary and secondary tumor growth in <i>ey</i>::<i>Dl</i>;<i>αPS4integrin<sup>RNAi</sup></i>, <i>ey</i>::<i>Dl</i>;<i>βPSintegrin<sup>RNAi</sup></i>, <i>ey</i>::<i>Dl</i>;<i>αPS2integrin<sup>RNAi</sup></i> and <i>ey</i>::<i>Dl</i>;<i>Timp<sup>RNAi</sup></i> flies. (C) Relative transcript levels of <i>DE-Cad</i>, <i>Cad86C</i> and <i>Cad99C</i> in eye-antennal discs of 3<sup>rd</sup> instar larvae of control animals (<i>Dcr2; ey::lacZ</i>) and in animals with reduced Ct activity (<i>Dcr2; ey::2xct<sup>RNAi</sup></i>). (D) Quantification of secondary tumor growth rates in different genetic backgrounds. Co-expression of E-Cad strongly reduces invasive tumor growth rates in <i>eyeful</i>+<i>ct<sup>RNAi</sup>;p35</i> flies. (E) Schematic drawing of a 3<sup>rd</sup> instar larva expressing GFP in eye-imaginal discs (either <i>ey</i>::<i>GFP</i> or <i>eyeful+GFP;ct<sup>RNAi</sup>;p35</i>). Locations of GFP-labeled eye-imaginal discs and the insect circulatory fluid, the hemolymph, are indicated by arrows. For analysis of the hemolymph, the insect circulatory fluid is extracted by bleeding out the larvae after cutting at the posterior end (indicated by dashed, blue line). (F) Left: Quantification of GFP-positive cells in the hemolymph of wild-type, <i>ey</i>::<i>GFP</i> and <i>eyeful</i>+<i>GFP</i>;<i>ct<sup>RNAi</sup></i>;<i>p35</i> 3<sup>rd</sup> instar larvae. Right: Relative <i>GFP</i> transcript levels in the hemolymph of <i>ey</i>::<i>GFP</i> and <i>eyeful</i>+<i>GFP</i>;<i>ct<sup>RNAi</sup></i>;<i>p35</i> 3<sup>rd</sup> instar larvae.</p>", "links"=>[], "tags"=>["induced", "ct", "depletion", "changes", "adhesive"], "article_id"=>338437, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Zongzhao Zhai", "Nati Ha", "Fani Papagiannouli", "Anne Hamacher-Brady", "Nathan Brady", "Sebastian Sorge", "Daniela Bezdan", "Ingrid Lohmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002582.g005", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Invasive_tumor_growth_induced_by_Ct_depletion_is_due_to_changes_in_adhesive_cell_properties_/338437", "title"=>"Invasive tumor growth induced by Ct depletion is due to changes in adhesive cell properties.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:20:37"}

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Relative Metric

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