Src family kinases (SFKs) are commonly over-expressed and/or activated in glioblastoma multiforme (GBM), where they serve as key mediators of GBM cell proliferation, survival, invasion and angiogenesis. Mechanisms of allosteric SFK activation are well described; however, the SFK Fyn is commonly up-regulated at the mRNA level in multiple human cancers, including GBM, where the mode of increased expression is poorly understood. Since activating mutations in the epidermal growth factor receptor (EGFR) are commonly occurring in GBM, we examined whether EGFR could induce Fyn expression. Here, we found that wild-type EGFR, and to a greater extent hyper-activating EGFR mutants, EGFRΔIII and R108K, induce a substantial up-regulation of Fyn expression. Furthermore, it was determined that Fyn expression is up-regulated across a panel of patient-derived GBM stem cells (GSCs) relative to normal progenitor controls. Inhibition of Fyn proved to be biologically relevant, as Fyn depletion significantly (pp
","abstract_html":"<p>Src family kinases (SFKs) are commonly over-expressed and/or activated in glioblastoma multiforme (GBM), where they serve as key mediators of GBM cell proliferation, survival, invasion and angiogenesis. Mechanisms of allosteric SFK activation are well described; however, the SFK Fyn is commonly up-regulated at the mRNA level in multiple human cancers, including GBM, where the mode of increased expression is poorly understood. Since activating mutations in the epidermal growth factor receptor (EGFR) are commonly occurring in GBM, we examined whether EGFR could induce Fyn expression. Here, we found that wild-type EGFR, and to a greater extent hyper-activating EGFR mutants, EGFRΔIII and R108K, induce a substantial up-regulation of Fyn expression. Furthermore, it was determined that Fyn expression is up-regulated across a panel of patient-derived GBM stem cells (GSCs) relative to normal progenitor controls. Inhibition of Fyn proved to be biologically relevant, as Fyn depletion significantly (<em>p</em>p</p>","abstract_has_math":false,"creators":["Johnson, Blake P"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Joya Chandra, Ph.D.","Gary Gallick, Ph.D.","Candelaria Gomez-Manzano, M.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-12-01T08:00:00Z","date_published":"2014-12-01T08:00:00Z","updated_at":"2026-07-24T05:50:02Z","subjects":["EGFR; Glioblastoma; SRC","Cancer Biology","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/539","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Joya Chandra, Ph.D.","Gary Gallick, Ph.D.","Candelaria Gomez-Manzano, M.D."]},{"key":"dc:creator","label":"Author","values":["Johnson, Blake P"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2015-06-19T07:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation (PhD)"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["EGFR; Glioblastoma; SRC","Cancer Biology","Medicine and Health Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/539"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Src family kinases (SFKs) are commonly over-expressed and/or activated in glioblastoma multiforme (GBM), where they serve as key mediators of GBM cell proliferation, survival, invasion and angiogenesis. Mechanisms of allosteric SFK activation are well described; however, the SFK Fyn is commonly up-regulated at the mRNA level in multiple human cancers, including GBM, where the mode of increased expression is poorly understood. Since activating mutations in the epidermal growth factor receptor (EGFR) are commonly occurring in GBM, we examined whether EGFR could induce Fyn expression. Here, we found that wild-type EGFR, and to a greater extent hyper-activating EGFR mutants, EGFRΔIII and R108K, induce a substantial up-regulation of Fyn expression. Furthermore, it was determined that Fyn expression is up-regulated across a panel of patient-derived GBM stem cells (GSCs) relative to normal progenitor controls. Inhibition of Fyn proved to be biologically relevant, as Fyn depletion significantly (pp
"]},{"key":"dc:title","label":"Title","values":["Epidermal Growth Factor Receptor Induces Fyn Expression Via Up-Regulation of P47Phox In Glioblastoma Multiforme"]}]}],"canonical_facts":{"dc:contributor":["Joya Chandra, Ph.D.","Gary Gallick, Ph.D.","Candelaria Gomez-Manzano, M.D."],"dc:creator":["Johnson, Blake P"],"dc:date.available":["2015-06-19T07:00:00Z"],"dc:description.abstract":["Src family kinases (SFKs) are commonly over-expressed and/or activated in glioblastoma multiforme (GBM), where they serve as key mediators of GBM cell proliferation, survival, invasion and angiogenesis. Mechanisms of allosteric SFK activation are well described; however, the SFK Fyn is commonly up-regulated at the mRNA level in multiple human cancers, including GBM, where the mode of increased expression is poorly understood. Since activating mutations in the epidermal growth factor receptor (EGFR) are commonly occurring in GBM, we examined whether EGFR could induce Fyn expression. Here, we found that wild-type EGFR, and to a greater extent hyper-activating EGFR mutants, EGFRΔIII and R108K, induce a substantial up-regulation of Fyn expression. Furthermore, it was determined that Fyn expression is up-regulated across a panel of patient-derived GBM stem cells (GSCs) relative to normal progenitor controls. Inhibition of Fyn proved to be biologically relevant, as Fyn depletion significantly (pp
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/539"],"dc:subject":["EGFR; Glioblastoma; SRC","Cancer Biology","Medicine and Health Sciences"],"dc:title":["Epidermal Growth Factor Receptor Induces Fyn Expression Via Up-Regulation of P47Phox In Glioblastoma Multiforme"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:50:02Z"}