{"id":{"repo_id":"nus","oai_identifier":"oai:scholarbank.nus.edu.sg:10635/230517"},"canonical_url":"https://search.dev.ndltd.org/etd/nus/oai:scholarbank.nus.edu.sg:10635/230517","repository":{"repo_id":"nus","name":"National University of Singapore","base_url":"https://scholarbank.nus.edu.sg/oai/request"},"display":{"title":"TUMOR-PROMOTING FUNCTION AND MOLECULAR REGULATION OF TSPAN8 IN LIVER CANCER","abstract":"TSPAN8 is an integral plasma membrane protein that belongs to the tetraspanin superfamily. In this study, we found that TSPAN8 is highly expressed in cholangiocytes but absent in hepatocytes in the healthy liver. Remarkably, its expression is robustly switched on in transformed hepatocytes in two liver cancer models induced by DEN and overexpression of Neu respectively. Moreover, germline whole-body knockout of TSPAN8 significantly suppresses the tumor development in the DEN-induced liver cancer model. Using CRISPR/Cas9 knockout approach, we demonstrated the critical role of TSPAN8 in the invasion and anchorage-independent colony formation of liver cancer cells. Moreover, orthotopic implantation of mouse liver cancer cells into synergetic recipient mice further unravelled that expression of TSPAN8 is required for their tumorigenesis. To discover the key regulators of TSPAN8, we conducted sequential genome-wide loss-of-function CRISPR screens based on its cell surface expression. We identified that modification of biantennary N-glycans and synthesis of lacto-series glycolipids mediated by a SPPL3/B3GNT5 axis are important for cell surface presentation of TSPAN8 and other tetraspanins. Collectively, our findings unmasked the potential of TSPAN8 as a diagnostic biomarker and therapeutic target in liver cancer and provided novel insights into its molecular regulation.","abstract_html":"TSPAN8 is an integral plasma membrane protein that belongs to the tetraspanin superfamily. In this study, we found that TSPAN8 is highly expressed in cholangiocytes but absent in hepatocytes in the healthy liver. Remarkably, its expression is robustly switched on in transformed hepatocytes in two liver cancer models induced by DEN and overexpression of Neu respectively. Moreover, germline whole-body knockout of TSPAN8 significantly suppresses the tumor development in the DEN-induced liver cancer model. Using CRISPR/Cas9 knockout approach, we demonstrated the critical role of TSPAN8 in the invasion and anchorage-independent colony formation of liver cancer cells. Moreover, orthotopic implantation of mouse liver cancer cells into synergetic recipient mice further unravelled that expression of TSPAN8 is required for their tumorigenesis. To discover the key regulators of TSPAN8, we conducted sequential genome-wide loss-of-function CRISPR screens based on its cell surface expression. We identified that modification of biantennary N-glycans and synthesis of lacto-series glycolipids mediated by a SPPL3/B3GNT5 axis are important for cell surface presentation of TSPAN8 and other tetraspanins. Collectively, our findings unmasked the potential of TSPAN8 as a diagnostic biomarker and therapeutic target in liver cancer and provided novel insights into its molecular regulation.","abstract_has_math":false,"creators":["YANG JICHENG"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-04-20","date_published":"2022-04-20","updated_at":"2026-07-24T03:32:56Z","subjects":["Glyco-lipid","SPPL3","N-glycosylation","Tetraspanins","Liver cancer","Tetraspanin-8"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["YANG JICHENG"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2022-04-20"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://scholarbank.nus.edu.sg/handle/10635/230517"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Glyco-lipid","SPPL3","N-glycosylation","Tetraspanins","Liver cancer","Tetraspanin-8"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://scholarbank.nus.edu.sg/bitstreams/431311de-55a3-4442-9f11-0e6187b2dbfd/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["TSPAN8 is an integral plasma membrane protein that belongs to the tetraspanin superfamily. In this study, we found that TSPAN8 is highly expressed in cholangiocytes but absent in hepatocytes in the healthy liver. Remarkably, its expression is robustly switched on in transformed hepatocytes in two liver cancer models induced by DEN and overexpression of Neu respectively. Moreover, germline whole-body knockout of TSPAN8 significantly suppresses the tumor development in the DEN-induced liver cancer model. Using CRISPR/Cas9 knockout approach, we demonstrated the critical role of TSPAN8 in the invasion and anchorage-independent colony formation of liver cancer cells. Moreover, orthotopic implantation of mouse liver cancer cells into synergetic recipient mice further unravelled that expression of TSPAN8 is required for their tumorigenesis. To discover the key regulators of TSPAN8, we conducted sequential genome-wide loss-of-function CRISPR screens based on its cell surface expression. We identified that modification of biantennary N-glycans and synthesis of lacto-series glycolipids mediated by a SPPL3/B3GNT5 axis are important for cell surface presentation of TSPAN8 and other tetraspanins. Collectively, our findings unmasked the potential of TSPAN8 as a diagnostic biomarker and therapeutic target in liver cancer and provided novel insights into its molecular regulation."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["17b849b9eb1d1241e1aedf5265dd29d3","d5ed4168c65466c8bdd95c8a68fe289d"]},{"key":"dc:title","label":"Title","values":["TUMOR-PROMOTING FUNCTION AND MOLECULAR REGULATION OF TSPAN8 IN LIVER CANCER"]}]}],"canonical_facts":{"dc:creator":["YANG JICHENG"],"dc:date.issued":["2022-04-20"],"dc:description.abstract":["TSPAN8 is an integral plasma membrane protein that belongs to the tetraspanin superfamily. In this study, we found that TSPAN8 is highly expressed in cholangiocytes but absent in hepatocytes in the healthy liver. Remarkably, its expression is robustly switched on in transformed hepatocytes in two liver cancer models induced by DEN and overexpression of Neu respectively. Moreover, germline whole-body knockout of TSPAN8 significantly suppresses the tumor development in the DEN-induced liver cancer model. Using CRISPR/Cas9 knockout approach, we demonstrated the critical role of TSPAN8 in the invasion and anchorage-independent colony formation of liver cancer cells. Moreover, orthotopic implantation of mouse liver cancer cells into synergetic recipient mice further unravelled that expression of TSPAN8 is required for their tumorigenesis. To discover the key regulators of TSPAN8, we conducted sequential genome-wide loss-of-function CRISPR screens based on its cell surface expression. We identified that modification of biantennary N-glycans and synthesis of lacto-series glycolipids mediated by a SPPL3/B3GNT5 axis are important for cell surface presentation of TSPAN8 and other tetraspanins. Collectively, our findings unmasked the potential of TSPAN8 as a diagnostic biomarker and therapeutic target in liver cancer and provided novel insights into its molecular regulation."],"dc:format.checksum.md5":["17b849b9eb1d1241e1aedf5265dd29d3","d5ed4168c65466c8bdd95c8a68fe289d"],"dc:identifier.uri":["https://scholarbank.nus.edu.sg/bitstreams/431311de-55a3-4442-9f11-0e6187b2dbfd/download"],"dc:relation.isreferencedby":["https://scholarbank.nus.edu.sg/handle/10635/230517"],"dc:subject":["Glyco-lipid","SPPL3","N-glycosylation","Tetraspanins","Liver cancer","Tetraspanin-8"],"dc:title":["TUMOR-PROMOTING FUNCTION AND MOLECULAR REGULATION OF TSPAN8 IN LIVER CANCER"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T03:32:56Z"}