{"id":{"repo_id":"queens","oai_identifier":"oai:queensu.scholaris.ca:1974/12464"},"canonical_url":"https://search.dev.ndltd.org/etd/queens/oai:queensu.scholaris.ca:1974/12464","repository":{"repo_id":"queens","name":"Queens University","base_url":"https://qspace.library.queensu.ca/server/oai/request"},"display":{"title":"Identifying the Molecular Mechanism of TAZ-Induced Lung Tumorigenesis","abstract":"The transcriptional co-activator with PDZ-binding domain (TAZ) is a transcriptional co-activator and downstream component of the tumor suppressor Hippo pathway that plays critical roles in organ size control, stem cell self-renewal, tumorigenesis and drug resistance. Recently, TAZ has been identified as a novel oncogene that is overexpressed in non-small cell lung cancer (NSCLC) cells and mediates their proliferation, transformation and tumorigenesis. However, the molecular mechanism underlying TAZ-induced tumorigenesis remains largely unknown. In this study, we first established an in vivo xenograft mouse model by overexpressing the constitutively active TAZ-S89A in E10 (mouse) and HBE135 (human) immortalized lung epithelial cells. Next, the gene expression profile of this model was analyzed by performing next-generation sequencing (RNA-seq) which led to identifying several novel genes transcriptionally upregulated by TAZ such as INHBA, KLF5, BMPs, FGFs, etc. Interestingly, we identified PI3K and TGF-ß signaling pathways as mediators of TAZ-induced cell proliferation and transformation, which were inhibited by using small molecule inhibitors specifically targeting these two signaling pathways. In addition, TAZ-induced cell proliferation and transformation were suppressed by disrupting the interaction between TAZ and its major binding transcription factor TEAD. Together, our study shows for the first time a new mechanism linking PI3K and TGF-ß pathways to TAZ-induced cell transformation, suggesting TAZ as a therapeutic target for NSCLC.","abstract_html":"The transcriptional co-activator with PDZ-binding domain (TAZ) is a transcriptional co-activator and downstream component of the tumor suppressor Hippo pathway that plays critical roles in organ size control, stem cell self-renewal, tumorigenesis and drug resistance. Recently, TAZ has been identified as a novel oncogene that is overexpressed in non-small cell lung cancer (NSCLC) cells and mediates their proliferation, transformation and tumorigenesis. However, the molecular mechanism underlying TAZ-induced tumorigenesis remains largely unknown. In this study, we first established an in vivo xenograft mouse model by overexpressing the constitutively active TAZ-S89A in E10 (mouse) and HBE135 (human) immortalized lung epithelial cells. Next, the gene expression profile of this model was analyzed by performing next-generation sequencing (RNA-seq) which led to identifying several novel genes transcriptionally upregulated by TAZ such as INHBA, KLF5, BMPs, FGFs, etc. Interestingly, we identified PI3K and TGF-ß signaling pathways as mediators of TAZ-induced cell proliferation and transformation, which were inhibited by using small molecule inhibitors specifically targeting these two signaling pathways. In addition, TAZ-induced cell proliferation and transformation were suppressed by disrupting the interaction between TAZ and its major binding transcription factor TEAD. Together, our study shows for the first time a new mechanism linking PI3K and TGF-ß pathways to TAZ-induced cell transformation, suggesting TAZ as a therapeutic target for NSCLC.","abstract_has_math":false,"creators":["Alharbi, Adel"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Pathology and Molecular Medicine","school":null,"contributors":[],"advisors":["Yang, Xiaolong"],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-09-17","date_published":"2014-09-17","updated_at":"2026-07-27T20:35:39Z","subjects":["TAZ","Tumorigenesis","Lung Cancer","Hippo Pathway"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1974/12464","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.department","label":"Department","values":["Pathology and Molecular Medicine"]},{"key":"dc:contributor.supervisor","label":"Supervisor","values":["Yang, Xiaolong"]},{"key":"dc:creator","label":"Author","values":["Alharbi, Adel"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2014-09-16 20:02:56.456"]},{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2014-09-17T17:08:45Z"]},{"key":"dc:date.issued","label":"Date","values":["2014-09-17"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["TAZ","Tumorigenesis","Lung Cancer","Hippo Pathway"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1974/12464"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2014-09-16 20:02:56.456"]},{"key":"dc:description.abstract","label":"Abstract","values":["The transcriptional co-activator with PDZ-binding domain (TAZ) is a transcriptional co-activator and downstream component of the tumor suppressor Hippo pathway that plays critical roles in organ size control, stem cell self-renewal, tumorigenesis and drug resistance. Recently, TAZ has been identified as a novel oncogene that is overexpressed in non-small cell lung cancer (NSCLC) cells and mediates their proliferation, transformation and tumorigenesis. However, the molecular mechanism underlying TAZ-induced tumorigenesis remains largely unknown. In this study, we first established an in vivo xenograft mouse model by overexpressing the constitutively active TAZ-S89A in E10 (mouse) and HBE135 (human) immortalized lung epithelial cells. Next, the gene expression profile of this model was analyzed by performing next-generation sequencing (RNA-seq) which led to identifying several novel genes transcriptionally upregulated by TAZ such as INHBA, KLF5, BMPs, FGFs, etc. Interestingly, we identified PI3K and TGF-ß signaling pathways as mediators of TAZ-induced cell proliferation and transformation, which were inhibited by using small molecule inhibitors specifically targeting these two signaling pathways. In addition, TAZ-induced cell proliferation and transformation were suppressed by disrupting the interaction between TAZ and its major binding transcription factor TEAD. Together, our study shows for the first time a new mechanism linking PI3K and TGF-ß pathways to TAZ-induced cell transformation, suggesting TAZ as a therapeutic target for NSCLC."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["M.Sc."]},{"key":"dc:title","label":"Title","values":["Identifying the Molecular Mechanism of TAZ-Induced Lung Tumorigenesis"]}]}],"canonical_facts":{"dc:contributor.department":["Pathology and Molecular Medicine"],"dc:contributor.supervisor":["Yang, Xiaolong"],"dc:creator":["Alharbi, Adel"],"dc:date":["2014-09-16 20:02:56.456"],"dc:date.accessioned":["2014-09-17T17:08:45Z"],"dc:date.issued":["2014-09-17"],"dc:description":["Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2014-09-16 20:02:56.456"],"dc:description.abstract":["The transcriptional co-activator with PDZ-binding domain (TAZ) is a transcriptional co-activator and downstream component of the tumor suppressor Hippo pathway that plays critical roles in organ size control, stem cell self-renewal, tumorigenesis and drug resistance. Recently, TAZ has been identified as a novel oncogene that is overexpressed in non-small cell lung cancer (NSCLC) cells and mediates their proliferation, transformation and tumorigenesis. However, the molecular mechanism underlying TAZ-induced tumorigenesis remains largely unknown. In this study, we first established an in vivo xenograft mouse model by overexpressing the constitutively active TAZ-S89A in E10 (mouse) and HBE135 (human) immortalized lung epithelial cells. Next, the gene expression profile of this model was analyzed by performing next-generation sequencing (RNA-seq) which led to identifying several novel genes transcriptionally upregulated by TAZ such as INHBA, KLF5, BMPs, FGFs, etc. Interestingly, we identified PI3K and TGF-ß signaling pathways as mediators of TAZ-induced cell proliferation and transformation, which were inhibited by using small molecule inhibitors specifically targeting these two signaling pathways. In addition, TAZ-induced cell proliferation and transformation were suppressed by disrupting the interaction between TAZ and its major binding transcription factor TEAD. Together, our study shows for the first time a new mechanism linking PI3K and TGF-ß pathways to TAZ-induced cell transformation, suggesting TAZ as a therapeutic target for NSCLC."],"dc:description.degree":["M.Sc."],"dc:identifier.uri":["http://hdl.handle.net/1974/12464"],"dc:language.iso":["eng"],"dc:subject":["TAZ","Tumorigenesis","Lung Cancer","Hippo Pathway"],"dc:title":["Identifying the Molecular Mechanism of TAZ-Induced Lung Tumorigenesis"],"dc:type":["thesis"]},"updated_at":"2026-07-27T20:35:39Z"}