To determine how tetraspanin KAI1/CD82, a tumor metastasis suppressor, inhibits cell migration, we assessed which motility-related cellular events are altered by KAI1/CD82 and how KAI1/CD82 regulates these events. We found that KAI1/CD82-overexpressing cancer cells exhibit various morphologies but typically display elongated cellular extensions and a lack of lamellipodia. Live imaging demonstrated that the formation of lamellipodia and retraction of extensions were deficient upon KAI1/CD82 overexpression.
The deficiency in developing motility-related cellular events was accompanied by defects in actin cortical network and stress fiber formations. Notably, actin polymerization was attenuated by KAI1/CD82. Although Rac1 activity was diminished upon KAI1/CD82 expression, Rac1 could not rescue lamellipodia formation because Rac1 activity is not required for this process in Du145 prostate cancer cells. Surprisingly, RhoA activity was upregulated upon KAI1/CD82 overexpression despite the loss of stress fiber and lack of cellular retraction, suggesting that enhanced RhoA activity is a compensatory effect resulting form impaired actin polymerization. Cofilin, an effector of both Rac and Rho, cannot translocate to the cell periphery in KAI1/CD82-overexpressing cells to facilitate lamellipodia formation, though the total and active cofilin proteins remain unchanged.
In summary, we demonstrate that KAI1/CD82 inhibits protrusion and retraction events crucial for cell movement by disrupting actin cortical network and stress fiber formations. At the molecular level, KAI1/CD82 impairs actin polymerization by unbalancing Rac1 and RhoA activities. KAI1/CD82-induced disruption of actin organization likely results from the suppression of common signaling steps of multiple pathways but is alleviated by cell-cell adhesion.
","abstract_html":"<p>To determine how tetraspanin KAI1/CD82, a tumor metastasis suppressor, inhibits cell migration, we assessed which motility-related cellular events are altered by KAI1/CD82 and how KAI1/CD82 regulates these events. We found that KAI1/CD82-overexpressing cancer cells exhibit various morphologies but typically display elongated cellular extensions and a lack of lamellipodia. Live imaging demonstrated that the formation of lamellipodia and retraction of extensions were deficient upon KAI1/CD82 overexpression.</p> <p>The deficiency in developing motility-related cellular events was accompanied by defects in actin cortical network and stress fiber formations. Notably, actin polymerization was attenuated by KAI1/CD82. Although Rac1 activity was diminished upon KAI1/CD82 expression, Rac1 could not rescue lamellipodia formation because Rac1 activity is not required for this process in Du145 prostate cancer cells. Surprisingly, RhoA activity was upregulated upon KAI1/CD82 overexpression despite the loss of stress fiber and lack of cellular retraction, suggesting that enhanced RhoA activity is a compensatory effect resulting form impaired actin polymerization. Cofilin, an effector of both Rac and Rho, cannot translocate to the cell periphery in KAI1/CD82-overexpressing cells to facilitate lamellipodia formation, though the total and active cofilin proteins remain unchanged.</p> <p>In summary, we demonstrate that KAI1/CD82 inhibits protrusion and retraction events crucial for cell movement by disrupting actin cortical network and stress fiber formations. At the molecular level, KAI1/CD82 impairs actin polymerization by unbalancing Rac1 and RhoA activities. KAI1/CD82-induced disruption of actin organization likely results from the suppression of common signaling steps of multiple pathways but is alleviated by cell-cell adhesion.</p>","abstract_has_math":false,"creators":["Liu, Wei"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Interdisciplinary Program","degree_department":null,"school":null,"contributors":["Xin Zhang, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2007,"date_issued":"2007-12-01T08:00:00Z","date_published":"2007-12-01T08:00:00Z","updated_at":"2026-07-24T05:00:11Z","subjects":["KAI1/CD82","tetraspanins","actin","lamellipodia","Rac","and Rho","Medical Cell Biology","Medical Sciences","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/155","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Xin Zhang, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Liu, Wei"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-06-08T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Interdisciplinary Program"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"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":["KAI1/CD82","tetraspanins","actin","lamellipodia","Rac","and Rho","Medical Cell Biology","Medical Sciences","Medicine and Health Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/155"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["To determine how tetraspanin KAI1/CD82, a tumor metastasis suppressor, inhibits cell migration, we assessed which motility-related cellular events are altered by KAI1/CD82 and how KAI1/CD82 regulates these events. We found that KAI1/CD82-overexpressing cancer cells exhibit various morphologies but typically display elongated cellular extensions and a lack of lamellipodia. Live imaging demonstrated that the formation of lamellipodia and retraction of extensions were deficient upon KAI1/CD82 overexpression.
The deficiency in developing motility-related cellular events was accompanied by defects in actin cortical network and stress fiber formations. Notably, actin polymerization was attenuated by KAI1/CD82. Although Rac1 activity was diminished upon KAI1/CD82 expression, Rac1 could not rescue lamellipodia formation because Rac1 activity is not required for this process in Du145 prostate cancer cells. Surprisingly, RhoA activity was upregulated upon KAI1/CD82 overexpression despite the loss of stress fiber and lack of cellular retraction, suggesting that enhanced RhoA activity is a compensatory effect resulting form impaired actin polymerization. Cofilin, an effector of both Rac and Rho, cannot translocate to the cell periphery in KAI1/CD82-overexpressing cells to facilitate lamellipodia formation, though the total and active cofilin proteins remain unchanged.
In summary, we demonstrate that KAI1/CD82 inhibits protrusion and retraction events crucial for cell movement by disrupting actin cortical network and stress fiber formations. At the molecular level, KAI1/CD82 impairs actin polymerization by unbalancing Rac1 and RhoA activities. KAI1/CD82-induced disruption of actin organization likely results from the suppression of common signaling steps of multiple pathways but is alleviated by cell-cell adhesion.
"]},{"key":"dc:title","label":"Title","values":["Tetraspanin KAI1/CD82 inhibits cell migration-related cellular events via reorganizing actin network"]}]}],"canonical_facts":{"dc:contributor":["Xin Zhang, Ph.D."],"dc:creator":["Liu, Wei"],"dc:date.available":["2016-06-08T07:00:00Z"],"dc:description.abstract":["To determine how tetraspanin KAI1/CD82, a tumor metastasis suppressor, inhibits cell migration, we assessed which motility-related cellular events are altered by KAI1/CD82 and how KAI1/CD82 regulates these events. We found that KAI1/CD82-overexpressing cancer cells exhibit various morphologies but typically display elongated cellular extensions and a lack of lamellipodia. Live imaging demonstrated that the formation of lamellipodia and retraction of extensions were deficient upon KAI1/CD82 overexpression.
The deficiency in developing motility-related cellular events was accompanied by defects in actin cortical network and stress fiber formations. Notably, actin polymerization was attenuated by KAI1/CD82. Although Rac1 activity was diminished upon KAI1/CD82 expression, Rac1 could not rescue lamellipodia formation because Rac1 activity is not required for this process in Du145 prostate cancer cells. Surprisingly, RhoA activity was upregulated upon KAI1/CD82 overexpression despite the loss of stress fiber and lack of cellular retraction, suggesting that enhanced RhoA activity is a compensatory effect resulting form impaired actin polymerization. Cofilin, an effector of both Rac and Rho, cannot translocate to the cell periphery in KAI1/CD82-overexpressing cells to facilitate lamellipodia formation, though the total and active cofilin proteins remain unchanged.
In summary, we demonstrate that KAI1/CD82 inhibits protrusion and retraction events crucial for cell movement by disrupting actin cortical network and stress fiber formations. At the molecular level, KAI1/CD82 impairs actin polymerization by unbalancing Rac1 and RhoA activities. KAI1/CD82-induced disruption of actin organization likely results from the suppression of common signaling steps of multiple pathways but is alleviated by cell-cell adhesion.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/155"],"dc:subject":["KAI1/CD82","tetraspanins","actin","lamellipodia","Rac","and Rho","Medical Cell Biology","Medical Sciences","Medicine and Health Sciences"],"dc:title":["Tetraspanin KAI1/CD82 inhibits cell migration-related cellular events via reorganizing actin network"],"thesis:degree_discipline":["Interdisciplinary Program"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:00:11Z"}