FOXM1 Is an Oncogenic Mediator in Ewing Sarcoma
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{"title"=>"FOXM1 Is an Oncogenic Mediator in Ewing Sarcoma", "type"=>"journal", "authors"=>[{"first_name"=>"Laura", "last_name"=>"Christensen", "scopus_author_id"=>"35261832800"}, {"first_name"=>"Jay", "last_name"=>"Joo", "scopus_author_id"=>"35262192000"}, {"first_name"=>"Sean", "last_name"=>"Lee", "scopus_author_id"=>"55569496900"}, {"first_name"=>"Daniel", "last_name"=>"Wai", "scopus_author_id"=>"22949215300"}, {"first_name"=>"Timothy J.", "last_name"=>"Triche", "scopus_author_id"=>"7004983032"}, {"first_name"=>"William A.", "last_name"=>"May", "scopus_author_id"=>"7202153880"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"368187454", "doi"=>"10.1371/journal.pone.0054556", "sgr"=>"84872869719", "scopus"=>"2-s2.0-84872869719", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"23365673"}, "id"=>"10162067-f91f-3480-bff0-347b2d045f06", "abstract"=>"Ewing Family Tumors (Ewing Sarcoma and peripheral Primitive Neuroectodermal Tumor) are common bone and soft tissue malignancies of childhood, adolescence and young adulthood. Chromosomal translocation in these tumors produces fusion oncogenes of the EWS/ETS class, with EWS/FLI1 being by far the most common. EWS/ETS chimera are the only well established driver mutations in these tumors and they function as aberrant transcription factors. Understanding the downstream genes whose expression is modified has been a central approach to the study of these tumors. FOXM1 is a proliferation associated transcription factor which has increasingly been found to play a role in the pathogenesis of a wide range of human cancers. Here we demonstrate that FOXM1 is expressed in Ewing primary tumors and cell lines. Reduction in FOXM1 expression in Ewing cell lines results in diminished potential for anchorage independent growth. FOXM1 expression is enhanced by EWS/FLI1, though, unlike other tumor systems, it is not driven by expression of the EWS/FLI1 target GLI1. Thiostrepton is a compound known to inhibit FOXM1 by direct binding. We show that Thiostrepton diminishes FOXM1 expression in Ewing cell lines and this reduction reduces cell viability through an apoptotic mechanism. FOXM1 is involved in Ewing tumor pathogenesis and may prove to be a useful therapeutic target in Ewing tumors.", "link"=>"http://www.mendeley.com/research/foxm1-oncogenic-mediator-ewing-sarcoma", "reader_count"=>24, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>14, "Medicine and Dentistry"=>5, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}}, "reader_count_by_country"=>{"Czech Republic"=>1, "Switzerland"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/501066"], "description"=>"<p>A: Microarray data from Affymetrix Human Exon 1.0 ST (HuEx) Arrays reveal FOXM1 expression levels which are comparable to Neuroblastoma (NBL) and not statistically different (p = 0.12). B: Real time quantitative PCR for FOXM1 (all splice forms) confirms significant levels of transcript in primary Ewing Sarcoma tumor specimens and the Ewing cell line TC71, compared to CHLA57, a Schwannoma cell line, DU145, a Prostate Carcinoma cell line, cultured primary fibroblasts (Fibr.) and mature cerebellar tissue (Cereb.). C: Western blot for FOXM1 detects FOXM1 protein in 6/7 Ewing cell lines tested and in the Prostate cell line DU145.</p>", "links"=>[], "tags"=>["ewing"], "article_id"=>171582, "categories"=>["Cancer", "Genetics", "Medicine"], "users"=>["Laura Christensen", "Jay Joo", "Sean Lee", "Daniel Wai", "Timothy J. Triche", "William A. May"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054556.g001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FOXM1_expression_in_Ewing_Sarcoma_/171582", "title"=>"FOXM1 expression in Ewing Sarcoma.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:26:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/478378", "https://ndownloader.figshare.com/files/478384", "https://ndownloader.figshare.com/files/478388", "https://ndownloader.figshare.com/files/478390"], "description"=>"<div><p>Ewing Family Tumors (Ewing Sarcoma and peripheral Primitive Neuroectodermal Tumor) are common bone and soft tissue malignancies of childhood, adolescence and young adulthood. Chromosomal translocation in these tumors produces fusion oncogenes of the EWS/ETS class, with EWS/FLI1 being by far the most common. EWS/ETS chimera are the only well established driver mutations in these tumors and they function as aberrant transcription factors. Understanding the downstream genes whose expression is modified has been a central approach to the study of these tumors. FOXM1 is a proliferation associated transcription factor which has increasingly been found to play a role in the pathogenesis of a wide range of human cancers. Here we demonstrate that FOXM1 is expressed in Ewing primary tumors and cell lines. Reduction in FOXM1 expression in Ewing cell lines results in diminished potential for anchorage independent growth. FOXM1 expression is enhanced by EWS/FLI1, though, unlike other tumor systems, it is not driven by expression of the EWS/FLI1 target GLI1. Thiostrepton is a compound known to inhibit FOXM1 by direct binding. We show that Thiostrepton diminishes FOXM1 expression in Ewing cell lines and this reduction reduces cell viability through an apoptotic mechanism. FOXM1 is involved in Ewing tumor pathogenesis and may prove to be a useful therapeutic target in Ewing tumors.</p> </div>", "links"=>[], "tags"=>["foxm1", "oncogenic", "mediator", "ewing", "sarcoma"], "article_id"=>154267, "categories"=>["Cancer", "Genetics", "Medicine"], "users"=>["Laura Christensen", "Jay Joo", "Sean Lee", "Daniel Wai", "Timothy J. Triche", "William A. May"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054556.s001", "https://dx.doi.org/10.1371/journal.pone.0054556.s002", "https://dx.doi.org/10.1371/journal.pone.0054556.s003", "https://dx.doi.org/10.1371/journal.pone.0054556.s004"], "stats"=>{"downloads"=>4, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/FOXM1_Is_an_Oncogenic_Mediator_in_Ewing_Sarcoma__/154267", "title"=>"FOXM1 Is an Oncogenic Mediator in Ewing Sarcoma", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-01-24 01:11:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/501276"], "description"=>"<p> A: EWS/FLI1 lentiviral shRNA or a non-targeting control was used to derive polyclonal populations in four Ewing cell lines. By real time quantitative PCR, all demonstrate reduced EWS/FLI1 transcript and reduced FOXM1 transcript. All differences significant to p<$>\\scale 60%\\raster=\"rg1\"<$>0.05 by Student’s t-test as shown. B: Western blot for FOXM1 on the same cell lines demonstrates consistent reduction in FOXM1 protein. Fold change in band intensity is quantitated with ImageJ. C: Ewing cell lines transduced with GLI1 shRNA demonstrate reduction in the GLI1 transcript (p<$>\\scale 60%\\raster=\"rg1\"<$>0.05). However, no significant change in FOXM1 transcript is detected. D: Western blot of Ewing cell lines treated with GLI1 shRNA also reveals no reduction in FOXM1 protein.</p>", "links"=>[], "tags"=>["ewing", "lines", "gli1"], "article_id"=>171796, "categories"=>["Cancer", "Genetics", "Medicine"], "users"=>["Laura Christensen", "Jay Joo", "Sean Lee", "Daniel Wai", "Timothy J. Triche", "William A. May"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054556.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FOXM1_expression_in_Ewing_cell_lines_is_EWS_FLI1_dependent_but_not_GLI1_dependent_/171796", "title"=>"FOXM1 expression in Ewing cell lines is EWS/FLI1 dependent but not GLI1 dependent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:29:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/501166"], "description"=>"<p> A: Three Ewing cell lines were transduced with either of two FOXM1 lentiviral shRNA or a nontargeting Luciferase control and polyclonal lines were selected with Puromycin. Real time quantitative PCR for FOXM1 shows significant reduction in FOXM1 transcript. All differences significant to p<$>\\scale 60%\\raster=\"rg1\"<$>0.05 by Student’s t-test. B: Cell lines transduced with FOXM1-HP1 confirm a significant reduction in FOXM1 protein. C: Three Ewing cell lines with FOXM1 shRNA are plated in soft agar and compared to non-targeting control. All three demonstrate reduction in colony formation with either FOXM1 shRNA.</p>", "links"=>[], "tags"=>["knockdown", "anchorage", "ewing"], "article_id"=>171686, "categories"=>["Cancer", "Genetics", "Medicine"], "users"=>["Laura Christensen", "Jay Joo", "Sean Lee", "Daniel Wai", "Timothy J. Triche", "William A. May"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054556.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FOXM1_knockdown_reduces_anchorage_independent_growth_in_Ewing_cell_lines_/171686", "title"=>"FOXM1 knockdown reduces anchorage independent growth in Ewing cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:28:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/501373"], "description"=>"<p> A: Ewing cell lines were treated for 16 hours with Thiostrepton at increasing concentrations. Real time quantitative PCR shows a reduction of FOXM1 transcript. B: Ewing cell lines treated with 5 mcM Thiostrepton for 36–72 hours show decreased FOXM1 protein on western blot. C: Treatment of Ewing cell lines with increasing quantities of Thiostrepton for 72 hours results in reduced numbers of viable cells compared to diluent controls. D: Ewing cell lines treated as in panel B show cleavage of PARP, an indicator of apoptosis.</p>", "links"=>[], "tags"=>["foxm1", "ewing", "producing", "diminished", "viability", "apoptotic"], "article_id"=>171889, "categories"=>["Cancer", "Genetics", "Medicine"], "users"=>["Laura Christensen", "Jay Joo", "Sean Lee", "Daniel Wai", "Timothy J. Triche", "William A. May"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054556.g004", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Thiostrepton_reduces_FOXM1_expression_in_Ewing_cell_lines_producing_diminished_cell_viability_by_an_apoptotic_mechanism_/171889", "title"=>"Thiostrepton reduces FOXM1 expression in Ewing cell lines, producing diminished cell viability by an apoptotic mechanism.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:31:29"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"1", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[266, 468, 593, 703, 804, 903, 993, 1084, 1171, 1256, 1339, 1422, 1492]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[272, 472, 600, 713, 815, 911, 1004, 1094, 1185, 1273, 1358, 1441]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Oncology", "average_usage"=>[249, 468, 599, 718, 820, 920, 1008, 1093, 1181, 1281, 1357, 1444, 1517]}]}
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