{"id":{"repo_id":"kings","oai_identifier":"oai:kclpure.kcl.ac.uk:studenttheses/1f08ad93-6216-46de-80a6-2efb8b9cc131"},"canonical_url":"https://search.dev.ndltd.org/etd/kings/oai:kclpure.kcl.ac.uk:studenttheses/1f08ad93-6216-46de-80a6-2efb8b9cc131","repository":{"repo_id":"kings","name":"King's College London","base_url":"https://kclpure.kcl.ac.uk/ws/oai"},"display":{"title":"The role of PAK6 in HGF-induced prostate cancer cell migration","abstract":"Cell migration plays a significant role in carcinoma metastasis in which cancer cells move from the primary site and establish tumours at a secondary location. During tumour progression cancer cells can assume a migratory phenotype which is characterised by cell-cell dissociation and single cells adopting a migratory morphology. Hepatocyte growth factor (HGF) signalling is known to induce cell-cell dissociation and is associated with prostate carcinoma progression. HGF-induced cell-cell dissociation and migration require the activity of the Rho family GTPases Rho A, Racl and Cdc42 and their effector proteins, p21-activated kinases (PAKs), which are a family of mammalian serine/threonine protein kinases. PAK6, a PAK family member, is over-expressed in prostate cancer but little is known about its function in cells. This project investigated the potential role of PAK6 downstream of HGF in DU145 colony-forming prostate cancer cells. These cells exhibit prominent epithelial-cadherin (E-cadherin)-associated cell-cell junctions and ’scatter’ upon HGF stimulation. Studies described here show that HGF addition increases PAK6 autophosphorylation and that PAK6 depletion inhibits HGF-induced DU145 cell scattering where these cells retain junctional E-cadherin. Moreover, PAK6 over-expression induces cell elongation and colony escape in unstimulated DU145 cells and PAK6 localises to E-cadherin positive cell junctions. Functional studies identified IQ motif containing GTPase activating protein 1 (IQGAP1) as a PAK6 binding partner in DU145 cells. Furthermore, PAK6 interacts with IQGAP1 in an HGF-dependent manner and both proteins act synergistically to induce cell colony escape. Additional studies suggest a complex relationship between IQGAP1, PAK6 and E-cadherin during HGF-induced junctional disassembly where IQGAP1 mediates PAK6 activity.","abstract_html":"Cell migration plays a significant role in carcinoma metastasis in which cancer cells move from the primary site and establish tumours at a secondary location. During tumour progression cancer cells can assume a migratory phenotype which is characterised by cell-cell dissociation and single cells adopting a migratory morphology. Hepatocyte growth factor (HGF) signalling is known to induce cell-cell dissociation and is associated with prostate carcinoma progression. HGF-induced cell-cell dissociation and migration require the activity of the Rho family GTPases Rho A, Racl and Cdc42 and their effector proteins, p21-activated kinases (PAKs), which are a family of mammalian serine/threonine protein kinases. PAK6, a PAK family member, is over-expressed in prostate cancer but little is known about its function in cells. This project investigated the potential role of PAK6 downstream of HGF in DU145 colony-forming prostate cancer cells. These cells exhibit prominent epithelial-cadherin (E-cadherin)-associated cell-cell junctions and ’scatter’ upon HGF stimulation. Studies described here show that HGF addition increases PAK6 autophosphorylation and that PAK6 depletion inhibits HGF-induced DU145 cell scattering where these cells retain junctional E-cadherin. Moreover, PAK6 over-expression induces cell elongation and colony escape in unstimulated DU145 cells and PAK6 localises to E-cadherin positive cell junctions. Functional studies identified IQ motif containing GTPase activating protein 1 (IQGAP1) as a PAK6 binding partner in DU145 cells. Furthermore, PAK6 interacts with IQGAP1 in an HGF-dependent manner and both proteins act synergistically to induce cell colony escape. Additional studies suggest a complex relationship between IQGAP1, PAK6 and E-cadherin during HGF-induced junctional disassembly where IQGAP1 mediates PAK6 activity.","abstract_has_math":false,"creators":["Fram, Sally"],"institution":"King's College London","degree_name":"Doctor of Philosophy","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Wells, Claire Marie","Ridley, Anne"],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-10-1","date_published":"2012-10-1","updated_at":"2026-07-24T02:44:37Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:kclpure.kcl.ac.uk:studenttheses/1f08ad93-6216-46de-80a6-2efb8b9cc131"],"render_values":[{"text":"oai:kclpure.kcl.ac.uk:studenttheses/1f08ad93-6216-46de-80a6-2efb8b9cc131","href":null,"code":true}]}]},"links":{"outbound_url":"https://kclpure.kcl.ac.uk/portal/en/studentTheses/1f08ad93-6216-46de-80a6-2efb8b9cc131","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Wells, Claire Marie","Ridley, Anne"]},{"key":"dc:creator","label":"Author","values":["Fram, Sally"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012-10-1"]},{"key":"dc:date.issued","label":"Date","values":["2012-10-1"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Cancer Cell Biology & Imaging"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["King's College London"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://kclpure.kcl.ac.uk/portal/en/studentTheses/1f08ad93-6216-46de-80a6-2efb8b9cc131"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:kclpure.kcl.ac.uk:studenttheses/1f08ad93-6216-46de-80a6-2efb8b9cc131","https://kclpure.kcl.ac.uk/portal/en/studentTheses/1f08ad93-6216-46de-80a6-2efb8b9cc131"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://kclpure.kcl.ac.uk/portal/files/12607540/Studentthesis-Sally_Fram_2012.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Cell migration plays a significant role in carcinoma metastasis in which cancer cells move from the primary site and establish tumours at a secondary location. During tumour progression cancer cells can assume a migratory phenotype which is characterised by cell-cell dissociation and single cells adopting a migratory morphology. Hepatocyte growth factor (HGF) signalling is known to induce cell-cell dissociation and is associated with prostate carcinoma progression. HGF-induced cell-cell dissociation and migration require the activity of the Rho family GTPases Rho A, Racl and Cdc42 and their effector proteins, p21-activated kinases (PAKs), which are a family of mammalian serine/threonine protein kinases. PAK6, a PAK family member, is over-expressed in prostate cancer but little is known about its function in cells. This project investigated the potential role of PAK6 downstream of HGF in DU145 colony-forming prostate cancer cells. These cells exhibit prominent epithelial-cadherin (E-cadherin)-associated cell-cell junctions and ’scatter’ upon HGF stimulation. Studies described here show that HGF addition increases PAK6 autophosphorylation and that PAK6 depletion inhibits HGF-induced DU145 cell scattering where these cells retain junctional E-cadherin. Moreover, PAK6 over-expression induces cell elongation and colony escape in unstimulated DU145 cells and PAK6 localises to E-cadherin positive cell junctions. Functional studies identified IQ motif containing GTPase activating protein 1 (IQGAP1) as a PAK6 binding partner in DU145 cells. Furthermore, PAK6 interacts with IQGAP1 in an HGF-dependent manner and both proteins act synergistically to induce cell colony escape. Additional studies suggest a complex relationship between IQGAP1, PAK6 and E-cadherin during HGF-induced junctional disassembly where IQGAP1 mediates PAK6 activity."]},{"key":"dc:title","label":"Title","values":["The role of PAK6 in HGF-induced prostate cancer cell migration"]}]}],"canonical_facts":{"dc:contributor.advisor":["Wells, Claire Marie","Ridley, Anne"],"dc:creator":["Fram, Sally"],"dc:date":["2012-10-1"],"dc:date.issued":["2012-10-1"],"dc:description.abstract":["Cell migration plays a significant role in carcinoma metastasis in which cancer cells move from the primary site and establish tumours at a secondary location. During tumour progression cancer cells can assume a migratory phenotype which is characterised by cell-cell dissociation and single cells adopting a migratory morphology. Hepatocyte growth factor (HGF) signalling is known to induce cell-cell dissociation and is associated with prostate carcinoma progression. HGF-induced cell-cell dissociation and migration require the activity of the Rho family GTPases Rho A, Racl and Cdc42 and their effector proteins, p21-activated kinases (PAKs), which are a family of mammalian serine/threonine protein kinases. PAK6, a PAK family member, is over-expressed in prostate cancer but little is known about its function in cells. This project investigated the potential role of PAK6 downstream of HGF in DU145 colony-forming prostate cancer cells. These cells exhibit prominent epithelial-cadherin (E-cadherin)-associated cell-cell junctions and ’scatter’ upon HGF stimulation. Studies described here show that HGF addition increases PAK6 autophosphorylation and that PAK6 depletion inhibits HGF-induced DU145 cell scattering where these cells retain junctional E-cadherin. Moreover, PAK6 over-expression induces cell elongation and colony escape in unstimulated DU145 cells and PAK6 localises to E-cadherin positive cell junctions. Functional studies identified IQ motif containing GTPase activating protein 1 (IQGAP1) as a PAK6 binding partner in DU145 cells. Furthermore, PAK6 interacts with IQGAP1 in an HGF-dependent manner and both proteins act synergistically to induce cell colony escape. Additional studies suggest a complex relationship between IQGAP1, PAK6 and E-cadherin during HGF-induced junctional disassembly where IQGAP1 mediates PAK6 activity."],"dc:identifier":["oai:kclpure.kcl.ac.uk:studenttheses/1f08ad93-6216-46de-80a6-2efb8b9cc131","https://kclpure.kcl.ac.uk/portal/en/studentTheses/1f08ad93-6216-46de-80a6-2efb8b9cc131"],"dc:identifier.uri":["https://kclpure.kcl.ac.uk/portal/files/12607540/Studentthesis-Sally_Fram_2012.pdf"],"dc:language":["eng"],"dc:publisher.department":["Cancer Cell Biology & Imaging"],"dc:publisher.institution":["King's College London"],"dc:relation.isreferencedby":["https://kclpure.kcl.ac.uk/portal/en/studentTheses/1f08ad93-6216-46de-80a6-2efb8b9cc131"],"dc:title":["The role of PAK6 in HGF-induced prostate cancer cell migration"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral Thesis"],"dc:type.qualificationname":["Doctor of Philosophy"]},"updated_at":"2026-07-24T02:44:37Z"}