{"id":{"repo_id":"nus","oai_identifier":"oai:scholarbank.nus.edu.sg:10635/37561"},"canonical_url":"https://search.dev.ndltd.org/etd/nus/oai:scholarbank.nus.edu.sg:10635/37561","repository":{"repo_id":"nus","name":"National University of Singapore","base_url":"https://scholarbank.nus.edu.sg/oai/request"},"display":{"title":"Signaling Pathway Inhibitor Library Screening Reveals B-Catenin/TCF4 as a Novel Telomerase Regulator in Cancer cell lines","abstract":"Well-defined signaling pathway (Wnt, EGFR and JAK/STAT) inhibitors that are known to play important roles in cancer progression were screened to identify new telomerase regulators. Hits from the inhibitors libraries were verified in a wide range of cancer cell lines (stomach adenocarcinoma: AGS, breast cancer: MCF7, colorectal cancer: HCT116/LS174T) and are therefore expected to be general TA inhibitors for some of the major types of cancer. ?-catenin/TCF4 complex was identified as a novel TA regulator from the screen and was later found to inhibit TA via transcription regulation of hTERT (human TERT). Activation of the Wnt pathway either by Wnt ligand (Wnt-3a) or LiCl (activates Wnt signaling by inhibiting GSK-3?) treatment as well as overexpression of a constitutively active form of ?-catenin (?-N ?-catenin) up regulated hTERT mRNA expression and telomerase activity (TA) in cancer cell lines. On the other hand, knocking down of endogenous ?-catenin via shRNA reduces hTERT mRNA expression and TA. In addition, a ?-catenin/TCF4 consensus binding sequence from -659bp to -653 bp (5?-TGCAAAG-3?) upstream of transcription start site in hTERT promoter was also found and evidences from promoter studies, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, showed that ?-catenin/TCF4 bind to hTERT promoter in vivo and in vitro. Taken together, this is the first study has shown that Wnt signaling regulates telomerase via the transcription regulation of hTERT.","abstract_html":"Well-defined signaling pathway (Wnt, EGFR and JAK/STAT) inhibitors that are known to play important roles in cancer progression were screened to identify new telomerase regulators. Hits from the inhibitors libraries were verified in a wide range of cancer cell lines (stomach adenocarcinoma: AGS, breast cancer: MCF7, colorectal cancer: HCT116/LS174T) and are therefore expected to be general TA inhibitors for some of the major types of cancer. ?-catenin/TCF4 complex was identified as a novel TA regulator from the screen and was later found to inhibit TA via transcription regulation of hTERT (human TERT). Activation of the Wnt pathway either by Wnt ligand (Wnt-3a) or LiCl (activates Wnt signaling by inhibiting GSK-3?) treatment as well as overexpression of a constitutively active form of ?-catenin (?-N ?-catenin) up regulated hTERT mRNA expression and telomerase activity (TA) in cancer cell lines. On the other hand, knocking down of endogenous ?-catenin via shRNA reduces hTERT mRNA expression and TA. In addition, a ?-catenin/TCF4 consensus binding sequence from -659bp to -653 bp (5?-TGCAAAG-3?) upstream of transcription start site in hTERT promoter was also found and evidences from promoter studies, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, showed that ?-catenin/TCF4 bind to hTERT promoter in vivo and in vitro. Taken together, this is the first study has shown that Wnt signaling regulates telomerase via the transcription regulation of hTERT.","abstract_has_math":false,"creators":["TOH LING LING, JOELLE"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-01-11","date_published":"2013-01-11","updated_at":"2026-07-24T03:33:34Z","subjects":["β-CATENIN,TCF4,SIGNALING,SCREEN,TELOMERASE,CANCER"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["TOH LING LING, JOELLE"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2013-01-11"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://scholarbank.nus.edu.sg/handle/10635/37561"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["β-CATENIN,TCF4,SIGNALING,SCREEN,TELOMERASE,CANCER"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://scholarbank.nus.edu.sg/bitstreams/b57b1045-5344-4a44-991b-7e710f6ab0e5/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Well-defined signaling pathway (Wnt, EGFR and JAK/STAT) inhibitors that are known to play important roles in cancer progression were screened to identify new telomerase regulators. Hits from the inhibitors libraries were verified in a wide range of cancer cell lines (stomach adenocarcinoma: AGS, breast cancer: MCF7, colorectal cancer: HCT116/LS174T) and are therefore expected to be general TA inhibitors for some of the major types of cancer. ?-catenin/TCF4 complex was identified as a novel TA regulator from the screen and was later found to inhibit TA via transcription regulation of hTERT (human TERT). Activation of the Wnt pathway either by Wnt ligand (Wnt-3a) or LiCl (activates Wnt signaling by inhibiting GSK-3?) treatment as well as overexpression of a constitutively active form of ?-catenin (?-N ?-catenin) up regulated hTERT mRNA expression and telomerase activity (TA) in cancer cell lines. On the other hand, knocking down of endogenous ?-catenin via shRNA reduces hTERT mRNA expression and TA. In addition, a ?-catenin/TCF4 consensus binding sequence from -659bp to -653 bp (5?-TGCAAAG-3?) upstream of transcription start site in hTERT promoter was also found and evidences from promoter studies, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, showed that ?-catenin/TCF4 bind to hTERT promoter in vivo and in vitro. Taken together, this is the first study has shown that Wnt signaling regulates telomerase via the transcription regulation of hTERT."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["217a8af1bbe0ee79be3afab3e420ee53","2ceb33cee4ad2d58c844ba07bb17aad8"]},{"key":"dc:title","label":"Title","values":["Signaling Pathway Inhibitor Library Screening Reveals B-Catenin/TCF4 as a Novel Telomerase Regulator in Cancer cell lines"]}]}],"canonical_facts":{"dc:creator":["TOH LING LING, JOELLE"],"dc:date.issued":["2013-01-11"],"dc:description.abstract":["Well-defined signaling pathway (Wnt, EGFR and JAK/STAT) inhibitors that are known to play important roles in cancer progression were screened to identify new telomerase regulators. Hits from the inhibitors libraries were verified in a wide range of cancer cell lines (stomach adenocarcinoma: AGS, breast cancer: MCF7, colorectal cancer: HCT116/LS174T) and are therefore expected to be general TA inhibitors for some of the major types of cancer. ?-catenin/TCF4 complex was identified as a novel TA regulator from the screen and was later found to inhibit TA via transcription regulation of hTERT (human TERT). Activation of the Wnt pathway either by Wnt ligand (Wnt-3a) or LiCl (activates Wnt signaling by inhibiting GSK-3?) treatment as well as overexpression of a constitutively active form of ?-catenin (?-N ?-catenin) up regulated hTERT mRNA expression and telomerase activity (TA) in cancer cell lines. On the other hand, knocking down of endogenous ?-catenin via shRNA reduces hTERT mRNA expression and TA. In addition, a ?-catenin/TCF4 consensus binding sequence from -659bp to -653 bp (5?-TGCAAAG-3?) upstream of transcription start site in hTERT promoter was also found and evidences from promoter studies, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, showed that ?-catenin/TCF4 bind to hTERT promoter in vivo and in vitro. 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