Sonic Hedgehog-Gli1 Signaling Pathway Regulates the Epithelial Mesenchymal Transition (EMT) by Mediating a New Target Gene, S100A4, in Pancreatic Cancer Cells
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{"title"=>"Sonic hedgehog-Gli1 signaling pathway regulates the Epithelial Mesenchymal Transition (EMT) by mediating a new target gene, S100A4, in pancreatic cancer cells", "type"=>"journal", "authors"=>[{"first_name"=>"Xuanfu", "last_name"=>"Xu", "scopus_author_id"=>"55619296924"}, {"first_name"=>"Bin", "last_name"=>"Su", "scopus_author_id"=>"54790177400"}, {"first_name"=>"Chuangao", "last_name"=>"Xie", "scopus_author_id"=>"7401934697"}, {"first_name"=>"Shumei", "last_name"=>"Wei", "scopus_author_id"=>"7401765558"}, {"first_name"=>"Yingqun", "last_name"=>"Zhou", "scopus_author_id"=>"35207800500"}, {"first_name"=>"Hua", "last_name"=>"Liu", "scopus_author_id"=>"57193516647"}, {"first_name"=>"Weiqi", "last_name"=>"Dai", "scopus_author_id"=>"39862859800"}, {"first_name"=>"Ping", "last_name"=>"Cheng", "scopus_author_id"=>"55523756800"}, {"first_name"=>"Fan", "last_name"=>"Wang", "scopus_author_id"=>"55337168400"}, {"first_name"=>"Xiaorong", "last_name"=>"Xu", "scopus_author_id"=>"56296825500"}, {"first_name"=>"Chuanyong", "last_name"=>"Guo", "scopus_author_id"=>"7402496825"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"373644981", "sgr"=>"84905001546", "pmid"=>"25072505", "scopus"=>"2-s2.0-84905001546", "doi"=>"10.1371/journal.pone.0096441", "issn"=>"19326203"}, "id"=>"40e6e671-d2fa-351c-8b0d-89d0a77e824c", "abstract"=>"AIMS: The hedgehog signaling pathway plays an important role in EMT of pancreatic cancer cells, but the precise mechanisms remain elusive. Because S100A4 as a key EMT moleculer marker was found to be upregulated upon Gli1 in pancreatic cancer cells, we focused on the relationship between Shh-Gli1 signals and S100 genes family. METHODS: On the base of cDNA microarray data, we investigated regulating mechanism of Gli1 to some members of S100A genes family in pancreatic cancer cell lines firstly. Then, the regulation of Gli1 to S100A4 gene was studied by molecular biology assays and the pro-metastasis effection of Gli1-dependent S100A4 was investigated in vitro. Finally, the expressions of Shh, Gli1, S100A4 and E-cadherin in pancreatic cancer tissues were studied by using immunohistochemistry assays. RESULTS: Five members of the S100 genes family, S100A2, S100A4, S100A6, S100A11, and S100A14 were found to be downregulated significantly upon Gli1 knockdown. Gli1 enhancer prediction combining with in vitro data demonstrated that Gli1 primarily regulates S100A family members via cis-acting elements. Indeed, the data indicate S100A4 and vimentin genes were upregulated significantly by Shh/Gli1-expression increasing and E-cadherin was significantly reduced at the same time. Migration of PC cells was increased significantly in a dose-dependent manner of Gli1 expression (P<0.05) and siS100A4 significantly reversed the response of PC cells induced by L-Shh transduction (P<0.01). CONCLUSION: Our data establish a novel connection between Shh-Gli1 signaling and S100A4 regulation, which imply that S100A4 might be one of the key factors in EMT mediated by Shh-Gli1 signaling in pancreatic cancer.", "link"=>"http://www.mendeley.com/research/sonic-hedgehoggli1-signaling-pathway-regulates-epithelial-mesenchymal-transition-emt-mediating-new-t", "reader_count"=>27, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Researcher"=>8, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Researcher"=>8, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>6, "Medicine and Dentistry"=>5, "Agricultural and Biological Sciences"=>12, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United States"=>2}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1613347"], "description"=>"<p>A: cDNA microarray data about S100 gene family; B: The differential expression levels of partial members of S100 gene family by qRT-PCR. The expression of GAPDH is as a control. * <i>P</i><0.05, ** <i>P</i><0.01.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Molecular cell biology", "Computational biology", "genetics", "gene expression", "Gene regulation", "Molecular genetics", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Pancreatic cancer", "Basic cancer research", "s100"], "article_id"=>1121004, "categories"=>["Biological Sciences"], "users"=>["XuanFu Xu", "Bin Su", "Chuangao Xie", "Shumei Wei", "Yingqun Zhou", "Hua Liu", "WeiQi Dai", "Ping Cheng", "Fan Wang", "Xiaorong Xu", "ChuanYong Guo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0096441.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_the_S100_gene_family_/1121004", "title"=>"Expression of the S100 gene family.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:00:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1613350"], "description"=>"<p>M: DNA Marker; PC: RNA polymerase II antibody for XChIP positive control; IP: Gli1 XChIP; IGG: mouse IgG for XChIP random control; NC: β-actin antibody for XChIP negative control.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Molecular cell biology", "Computational biology", "genetics", "gene expression", "Gene regulation", "Molecular genetics", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Pancreatic cancer", "Basic cancer research", "gli1", "promoter", "genes", "aspc-1", "cells", "xchip-pcr"], "article_id"=>1121007, "categories"=>["Biological Sciences"], "users"=>["XuanFu Xu", "Bin Su", "Chuangao Xie", "Shumei Wei", "Yingqun Zhou", "Hua Liu", "WeiQi Dai", "Ping Cheng", "Fan Wang", "Xiaorong Xu", "ChuanYong Guo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0096441.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Binding_of_Gli1_to_promoter_region_of_S100A2_4_and_6_genes_in_AsPC_1_cells_analyzed_by_XChIP_PCR_assay_/1121007", "title"=>"Binding of Gli1 to promoter region of S100A2, 4 and 6 genes in AsPC-1 cells analyzed by XChIP-PCR assay.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:00:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1613353"], "description"=>"<p>A: S100A4 luciferase activity increases with increasing expression level of SHh in AsPC-1 cells. The pGL3-1.5 S100A4 and Renilla luciferase vectors were transiently transfected into L-Gli1i infected, L-C infected or L-Shh infected AsPC-1 cells respectively. Results were normalized for transfection efficiency using Renilla luciferase and the L-C infected group was arbitrarily given a value of 1. B: Relative luciferase activity of the S100A4 promoter Gli1 binding site mutants. AsPC-1 cells transfected by L-Shh were transiently transfected 5mg of each reporter construct including pGL3-1.5 S100A4, pGL3-1.5 S100A4 Mut1, Mut2 and Mut3 respectively. The pGL3-1.5 S100A4 was arbitrarily given a value of 1 and the activities of the other transfections were adjusted relative to this activity. C: Site 1 was responsible for Gli1 transcription. Relative luciferase activity from different AsPC-1 cell groups, L-Gli1i infection, L-Shh infection or L-C infection, transfected by different constructs, pGL3 1.5 S100A4 Mut 1–2, Mut 2–3 and Mut 1–3 with Renilla luciferase vectors. Results were normalized for transfection efficiency using Renilla luciferase and the L-C infected group was arbitrarily given a value of 1. * <i>P</i><0.05, ** <i>P</i><0.01.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Molecular cell biology", "Computational biology", "genetics", "gene expression", "Gene regulation", "Molecular genetics", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Pancreatic cancer", "Basic cancer research", "gli1", "binding", "sites", "s100a4"], "article_id"=>1121009, "categories"=>["Biological Sciences"], "users"=>["XuanFu Xu", "Bin Su", "Chuangao Xie", "Shumei Wei", "Yingqun Zhou", "Hua Liu", "WeiQi Dai", "Ping Cheng", "Fan Wang", "Xiaorong Xu", "ChuanYong Guo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0096441.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_effective_Gli1_binding_sites_on_the_S100A4_promoter_/1121009", "title"=>"Identification of effective Gli1 binding sites on the S100A4 promoter.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:00:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1613361"], "description"=>"<p>A: The relative transcription levels of Shh, Gli1, S100A4, E-cadherin and vimentin were regulated by L-Gli1i/L-Shh transduction. B: The relative transcription levels of S100A4, E-cadherin and vimentin in L-Shh transfected cells were reversed by siS100A4 transduction. C: The expression levels of Gli1, S100A4, E-cadherin and vimentin proteins regulated by L-Gli1i/L-Shh transduction. D: The expression levels of S100A4, E-cadherin and vimentin proteins were reversed by siS100A4 transduction. E: The invasion/migration of pancreatic cancer cells regulated by L-Gli1i/L-Shh transduction were analyzed by transwell assays. F: The invasion/migration of L-Shh transfected cells were reversed by siS100A4 transduction. * <i>P</i><0.05, ** <i>P</i><0.01.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Molecular cell biology", "Computational biology", "genetics", "gene expression", "Gene regulation", "Molecular genetics", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Pancreatic cancer", "Basic cancer research", "pathway", "promoting", "pancreatic", "cancer", "cells", "mediating"], "article_id"=>1121017, "categories"=>["Biological Sciences"], "users"=>["XuanFu Xu", "Bin Su", "Chuangao Xie", "Shumei Wei", "Yingqun Zhou", "Hua Liu", "WeiQi Dai", "Ping Cheng", "Fan Wang", "Xiaorong Xu", "ChuanYong Guo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0096441.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hh_signaling_pathway_promoting_invasion_migration_of_pancreatic_cancer_cells_through_mediating_S100A4_/1121017", "title"=>"Hh signaling pathway promoting invasion/migration of pancreatic cancer cells through mediating S100A4.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:00:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1613364"], "description"=>"<p>A: Strong cytoplasmic staining for Shh in pancreatic cancer cells (×400); B: Weakly positive staining for Shh in ductal complex of chronic pancreatitis tissues (×400); C: Weakly positive staining for Shh in islet cells of normal cancer side tissue (×200); D: Negtive staining for Shh in normal ductal epithelial/acinar cells of cancer side tissue (×200); E: Cancer cells show strong nuclear staining for Gli1 and normal cancer side tissues were negtive (×400); F: Strong positive perinuclear cytoplasmic and part nuclear staining for Gli1 in pancreatic cancer cells (×400); G: Strong positive cytoplasmic staining for S100A4 in pancreatic cancer cells (×400); H: Positive cytoplasmic staining for E-cadherin in pancreatic cancer cells. Black arrows point to positive staining area and white arrows point to negtive staining area.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Molecular cell biology", "Computational biology", "genetics", "gene expression", "Gene regulation", "Molecular genetics", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Pancreatic cancer", "Basic cancer research", "s100a4", "E-cadherin", "pancreatic", "cancer", "tissues"], "article_id"=>1121019, "categories"=>["Biological Sciences"], "users"=>["XuanFu Xu", "Bin Su", "Chuangao Xie", "Shumei Wei", "Yingqun Zhou", "Hua Liu", "WeiQi Dai", "Ping Cheng", "Fan Wang", "Xiaorong Xu", "ChuanYong Guo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0096441.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_Shh_Gli1_S100A4_and_E_cadherin_in_pancreatic_cancer_tissues_analyzed_by_immunohistochemistry_/1121019", "title"=>"Expression of Shh, Gli1, S100A4 and E-cadherin in pancreatic cancer tissues analyzed by immunohistochemistry.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:00:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1613365"], "description"=>"<p>The primers for XChIP assays.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Molecular cell biology", "Computational biology", "genetics", "gene expression", "Gene regulation", "Molecular genetics", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Pancreatic cancer", "Basic cancer research", "primers", "xchip"], "article_id"=>1121021, "categories"=>["Biological Sciences"], "users"=>["XuanFu Xu", "Bin Su", "Chuangao Xie", "Shumei Wei", "Yingqun Zhou", "Hua Liu", "WeiQi Dai", "Ping Cheng", "Fan Wang", "Xiaorong Xu", "ChuanYong Guo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0096441.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_primers_for_XChIP_assays_/1121021", "title"=>"The primers for XChIP assays.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-29 03:00:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1613366"], "description"=>"<p>The putative Gli1 biding sites in S100A gene family.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Molecular cell biology", "Computational biology", "genetics", "gene expression", "Gene regulation", "Molecular genetics", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Pancreatic cancer", "Basic cancer research", "putative", "gli1", "biding", "sites", "s100a"], "article_id"=>1121022, "categories"=>["Biological Sciences"], "users"=>["XuanFu Xu", "Bin Su", "Chuangao Xie", "Shumei Wei", "Yingqun Zhou", "Hua Liu", "WeiQi Dai", "Ping Cheng", "Fan Wang", "Xiaorong Xu", "ChuanYong Guo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0096441.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_putative_Gli1_biding_sites_in_S100A_gene_family_/1121022", "title"=>"The putative Gli1 biding sites in S100A gene family.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-29 03:00:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1613367"], "description"=>"<p>The primer sequences for real time RT-PCR assays.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Molecular cell biology", "Computational biology", "genetics", "gene expression", "Gene regulation", "Molecular genetics", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Pancreatic cancer", "Basic cancer research", "primer", "sequences", "rt-pcr"], "article_id"=>1121023, "categories"=>["Biological Sciences"], "users"=>["XuanFu Xu", "Bin Su", "Chuangao Xie", "Shumei Wei", "Yingqun Zhou", "Hua Liu", "WeiQi Dai", "Ping Cheng", "Fan Wang", "Xiaorong Xu", "ChuanYong Guo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0096441.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_primer_sequences_for_real_time_RT_PCR_assays_/1121023", "title"=>"The primer sequences for real time RT-PCR assays.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-29 03:00:14"}

PMC Usage Stats | Further Information

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Relative Metric

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