{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Omi J"],"funding":["Japan Agency for Medical Research and Development","Japan Science and Technology Agency Moonshot R&D Program","Japan Society for the Promotion of Science"],"pagination":["e202212074"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10694799"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["223(2)"],"pubmed_abstract":["Cancer cells harness lipid metabolism to promote their own survival. We screened 47 cancer cell lines for survival dependency on phosphatidylserine (PS) synthesis using a PS synthase 1 (PTDSS1) inhibitor and found that B cell lymphoma is highly dependent on PS. Inhibition of PTDSS1 in B cell lymphoma cells caused a reduction of PS and phosphatidylethanolamine levels and an increase of phosphoinositide levels. The resulting imbalance of the membrane phospholipidome lowered the activation threshold for B cell receptor (BCR), a B cell-specific survival mechanism. BCR hyperactivation led to aberrant elevation of downstream Ca2+ signaling and subsequent apoptotic cell death. In a mouse xenograft model, PTDSS1 inhibition efficiently suppressed tumor growth and prolonged survival. Our findings suggest that PS synthesis may be a critical vulnerability of malignant B cell lymphomas that can be targeted pharmacologically."],"journal":["The Journal of cell biology"],"pubmed_title":["Phosphatidylserine synthesis controls oncogenic B cell receptor signaling in B cell lymphoma."],"pmcid":["PMC10694799"],"funding_grant_id":["JPMJMS2023-11","JP21gm1210013","JP22ck0106533h0003","22K15272","JP21gm0010004h9905","21J00906","JPMJMS2023-15"],"pubmed_authors":["Sawada K","Yoshihama Y","Kono N","Omi J","Kato T","Aoki J"],"additional_accession":[]},"is_claimable":false,"name":"Phosphatidylserine synthesis controls oncogenic B cell receptor signaling in B cell lymphoma.","description":"Cancer cells harness lipid metabolism to promote their own survival. We screened 47 cancer cell lines for survival dependency on phosphatidylserine (PS) synthesis using a PS synthase 1 (PTDSS1) inhibitor and found that B cell lymphoma is highly dependent on PS. Inhibition of PTDSS1 in B cell lymphoma cells caused a reduction of PS and phosphatidylethanolamine levels and an increase of phosphoinositide levels. The resulting imbalance of the membrane phospholipidome lowered the activation threshold for B cell receptor (BCR), a B cell-specific survival mechanism. BCR hyperactivation led to aberrant elevation of downstream Ca2+ signaling and subsequent apoptotic cell death. In a mouse xenograft model, PTDSS1 inhibition efficiently suppressed tumor growth and prolonged survival. Our findings suggest that PS synthesis may be a critical vulnerability of malignant B cell lymphomas that can be targeted pharmacologically.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-05-28T16:27:13.933Z","creation":"2025-04-05T15:53:00.713Z"},"accession":"S-EPMC10694799","cross_references":{"pubmed":["38048228"],"doi":["10.1083/jcb.202212074"]}}