Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/37561
Title: Signaling Pathway Inhibitor Library Screening Reveals B-Catenin/TCF4 as a Novel Telomerase Regulator in Cancer cell lines
Authors: TOH LING LING, JOELLE
Keywords: β-CATENIN,TCF4,SIGNALING,SCREEN,TELOMERASE,CANCER
Issue Date: 11-Jan-2013
Source: TOH LING LING, JOELLE (2013-01-11). Signaling Pathway Inhibitor Library Screening Reveals B-Catenin/TCF4 as a Novel Telomerase Regulator in Cancer cell lines. ScholarBank@NUS Repository.
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.
URI: http://scholarbank.nus.edu.sg/handle/10635/37561
Appears in Collections:Master's Theses (Open)

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