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Leukocyte immunoglobulin-like receptor B1 (LILRB1) protects human multiple myeloma cells from ferroptosis by maintaining cholesterol homeostasis
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Leukocyte immunoglobulin-like receptor B1 (LILRB1) protects human multiple myeloma cells from ferroptosis by maintaining cholesterol homeostasis
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Journal Article
Leukocyte immunoglobulin-like receptor B1 (LILRB1) protects human multiple myeloma cells from ferroptosis by maintaining cholesterol homeostasis
2024
Overview
Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled proliferation of plasma cells in the bone marrow. MM patients with aggressive progression have poor survival, emphasizing the urgent need for identifying new therapeutic targets. Here, we show that the leukocyte immunoglobulin-like receptor B1 (LILRB1), a transmembrane receptor conducting negative immune response, is a top-ranked gene associated with poor prognosis in MM patients. LILRB1 deficiency inhibits MM progression in vivo by enhancing the ferroptosis of MM cells. Mechanistic studies reveal that LILRB1 forms a complex with the low-density lipoprotein receptor (LDLR) and LDLR adapter protein 1 (LDLRAP1) to facilitate LDL/cholesterol uptake. Loss of LILRB1 impairs cholesterol uptake but activates the de novo cholesterol synthesis pathway to maintain cellular cholesterol homeostasis, leading to the decrease of anti-ferroptotic metabolite squalene. Our study uncovers the function of LILRB1 in regulating cholesterol metabolism and protecting MM cells from ferroptosis, implicating LILRB1 as a promising therapeutic target for MM patients.
Patients with multiple myeloma need new therapeutic targets. The authors identify the transmembrane receptor LILRB1 as a potential target as it protects myeloma cells from ferroptosis by facilitating cholesterol uptake and maintaining cholesterol homeostasis and squalene levels.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 13/109
/ 13/31
/ 14/34
/ 14/5
/ 38/39
/ 38/61
/ 96
/ 96/95
/ Animals
/ Humanities and Social Sciences
/ Humans
/ Leukocyte Immunoglobulin-like Receptor B1 - metabolism
/ Low density lipoprotein receptors
/ Mice
/ Multiple Myeloma - metabolism
/ Multiple Myeloma - pathology
/ Science
/ Squalene
