生物
磷脂酰丝氨酸
癌症研究
B细胞
细胞凋亡
细胞
癌细胞
淋巴瘤
B细胞受体
细胞生长
B细胞淋巴瘤
程序性细胞死亡
磷脂酰乙醇胺
细胞培养
细胞生物学
癌症
免疫学
生物化学
磷脂
抗体
磷脂酰胆碱
遗传学
膜
作者
Jumpei Omi,Taiga Kato,Yohei Yoshihama,Koki Sawada,Nozomu Kono,Junken Aoki
标识
DOI:10.1083/jcb.202212074
摘要
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.
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