{"id":{"repo_id":"iupui","oai_identifier":"oai:scholarworks.indianapolis.iu.edu:1805/42652"},"canonical_url":"https://search.dev.ndltd.org/etd/iupui/oai:scholarworks.indianapolis.iu.edu:1805/42652","repository":{"repo_id":"iupui","name":"IUPUI","base_url":"https://scholarworks.indianapolis.iu.edu/server/oai/request"},"display":{"title":"Combined Inhibition of SREBP and m-TORC1 Signaling Synergistically Inhibits the Proliferation of B Cell Lymphoma","abstract":"Sterol regulatory element-binding protein (SREBP) signaling plays a crucial role in maintaining sterol homeostasis during B cell activation and the proliferation of germinal center B cells. It is unclear whether this pathway can be targeted to effectively treat B cell lymphoma. We discovered that inhibiting SREBP signaling or its downstream target HMG-CoA reductase (HMGCR) using Fatostatin or Simvastatin effectively restrains the proliferation of B cell lymphoma cells. However, B cell lymphoma cells activate the mTORC1-pS6 pathway in response to statin treatment, suggesting a possible mechanism to counteract statin-induced cell cycle arrest. Combining low dose statin treatment with the mTORC1 inhibitor rapamycin demonstrates a synergistic effect in inhibiting B cell lymphoma proliferation, cell cycle progression and lipid raft generation. These findings emphasize the potential of a combined therapy approach targeting both SREBP and mTORC1 as a novel treatment strategy for B cell lymphoma.","abstract_html":"Sterol regulatory element-binding protein (SREBP) signaling plays a crucial role in maintaining sterol homeostasis during B cell activation and the proliferation of germinal center B cells. It is unclear whether this pathway can be targeted to effectively treat B cell lymphoma. We discovered that inhibiting SREBP signaling or its downstream target HMG-CoA reductase (HMGCR) using Fatostatin or Simvastatin effectively restrains the proliferation of B cell lymphoma cells. However, B cell lymphoma cells activate the mTORC1-pS6 pathway in response to statin treatment, suggesting a possible mechanism to counteract statin-induced cell cycle arrest. Combining low dose statin treatment with the mTORC1 inhibitor rapamycin demonstrates a synergistic effect in inhibiting B cell lymphoma proliferation, cell cycle progression and lipid raft generation. These findings emphasize the potential of a combined therapy approach targeting both SREBP and mTORC1 as a novel treatment strategy for B cell lymphoma.","abstract_has_math":false,"creators":["Zhu, Zhenhan"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Luo, Wei"],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-06","date_published":"2024-06","updated_at":"2026-07-24T02:40:46Z","subjects":["Statins","SREBP","mTORC1","B cell lymphoma"],"languages":["en_US"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://doi.org/10.7912/5FFC-S592"],"render_values":[{"text":"https://doi.org/10.7912/5FFC-S592","href":"https://doi.org/10.7912/5FFC-S592","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/1805/42652","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Luo, Wei"]},{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["Capitano, Meagan L","Yuan, Xue"]},{"key":"dc:creator","label":"Author","values":["Zhu, Zhenhan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-08-06T09:16:37Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-08-06T09:16:37Z"]},{"key":"dc:date.issued","label":"Date","values":["2024-06"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Statins","SREBP","mTORC1","B cell lymphoma"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1805/42652","https://doi.org/10.7912/5FFC-S592"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["IUPUI"]},{"key":"dc:description.abstract","label":"Abstract","values":["Sterol regulatory element-binding protein (SREBP) signaling plays a crucial role in maintaining sterol homeostasis during B cell activation and the proliferation of germinal center B cells. It is unclear whether this pathway can be targeted to effectively treat B cell lymphoma. We discovered that inhibiting SREBP signaling or its downstream target HMG-CoA reductase (HMGCR) using Fatostatin or Simvastatin effectively restrains the proliferation of B cell lymphoma cells. However, B cell lymphoma cells activate the mTORC1-pS6 pathway in response to statin treatment, suggesting a possible mechanism to counteract statin-induced cell cycle arrest. Combining low dose statin treatment with the mTORC1 inhibitor rapamycin demonstrates a synergistic effect in inhibiting B cell lymphoma proliferation, cell cycle progression and lipid raft generation. These findings emphasize the potential of a combined therapy approach targeting both SREBP and mTORC1 as a novel treatment strategy for B cell lymphoma."]},{"key":"dc:title","label":"Title","values":["Combined Inhibition of SREBP and m-TORC1 Signaling Synergistically Inhibits the Proliferation of B Cell Lymphoma"]}]}],"canonical_facts":{"dc:contributor.advisor":["Luo, Wei"],"dc:contributor.other":["Capitano, Meagan L","Yuan, Xue"],"dc:creator":["Zhu, Zhenhan"],"dc:date.accessioned":["2024-08-06T09:16:37Z"],"dc:date.available":["2024-08-06T09:16:37Z"],"dc:date.issued":["2024-06"],"dc:description":["IUPUI"],"dc:description.abstract":["Sterol regulatory element-binding protein (SREBP) signaling plays a crucial role in maintaining sterol homeostasis during B cell activation and the proliferation of germinal center B cells. It is unclear whether this pathway can be targeted to effectively treat B cell lymphoma. We discovered that inhibiting SREBP signaling or its downstream target HMG-CoA reductase (HMGCR) using Fatostatin or Simvastatin effectively restrains the proliferation of B cell lymphoma cells. However, B cell lymphoma cells activate the mTORC1-pS6 pathway in response to statin treatment, suggesting a possible mechanism to counteract statin-induced cell cycle arrest. Combining low dose statin treatment with the mTORC1 inhibitor rapamycin demonstrates a synergistic effect in inhibiting B cell lymphoma proliferation, cell cycle progression and lipid raft generation. These findings emphasize the potential of a combined therapy approach targeting both SREBP and mTORC1 as a novel treatment strategy for B cell lymphoma."],"dc:identifier.uri":["https://hdl.handle.net/1805/42652","https://doi.org/10.7912/5FFC-S592"],"dc:language.iso":["en_US"],"dc:subject":["Statins","SREBP","mTORC1","B cell lymphoma"],"dc:title":["Combined Inhibition of SREBP and m-TORC1 Signaling Synergistically Inhibits the Proliferation of B Cell Lymphoma"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T02:40:46Z"}