| RRC ID |
78225
|
| 著者 |
Omi J, Kato T, Yoshihama Y, Sawada K, Kono N, Aoki J.
|
| タイトル |
Phosphatidylserine synthesis controls oncogenic B cell receptor signaling in B cell lymphoma.
|
| ジャーナル |
J Cell Biol
|
| 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.
|
| 巻・号 |
223(2)
|
| 公開日 |
2024-2-5
|
| DOI |
10.1083/jcb.202212074
|
| PII |
276442
|
| PMID |
38048228
|
| PMC |
PMC10694799
|
| MeSH |
Animals
Apoptosis
Humans
Lymphoma, B-Cell* / genetics
Mice
Nitrogenous Group Transferases / antagonists & inhibitors
Phosphatidylinositols
Phosphatidylserines* / biosynthesis
Receptors, Antigen, B-Cell* / metabolism
Signal Transduction
|
| リソース情報 |
| 遺伝子材料 |
tFucci(CA)2/pCSII-CMV (RDB15452)
YC3.60/pcDNA3 (RDB15135) |
