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Fatty acid binding proteins contribute to multiple myeloma cell maintenance through regulation of Myc, the unfolded protein response, and metabolism

ABSTRACT: Multiple myeloma (MM) is an incurable plasma cell malignancy that causes anemia, osteolysis, hypercalcemia, and organ failure, with only a 53% 5-years survival rate. Herein, we present data demonstrating a novel target in MM: the fatty acid binding protein (FABP) family. In clinical data, FABP5 represented a novel biomarker for more aggressive cancer. FABP inhibitors decreased tumor burden in vitro and in vivo and increased survival in immunocompetent and immunocompromised mouse models. FABP5 was the most highly expressed FABP member in myeloma cells, and the most essential for their survival. CRISPR-Cas9 generated FABP5-KO MM.1S cells showed inhibited growth potential. RNA-sequencing and metabolic analysis identified new pathways of action for the FABPs, including MYC, the unfolded protein response (UPR), and metabolic changes. Collectively, our results demonstrate that FABPs comprise a novel, targetable, and safe, therapeutic avenue for MM and other cancers, and suggest inhibiting FABPs may be worthy of further study.

ORGANISM(S): Homo sapiens

PROVIDER: GSE190699 | GEO | 2022/12/11

REPOSITORIES: GEO

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Mitochondrial integrity regulated by FABP5 is a cell-intrinsic checkpoint for Treg suppressive function

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2019-12-26 | GSE126245 | GEO

Fatty Acid Binding Protein 5 is a Novel Target in Multiple Myeloma

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Project description:Multiple myeloma (MM) is an incurable hematological malignancy of plasma cells. The maintenance of protein homeostasis is critical for the survival of MM cells. The excess paraprotein in MM cells undergoes clearance through proteasomes or lysosomes, two inter-connected yet independent pathways. While proteasome inhibitors (PIs) serve as fundamental agents significantly improving patient outcomes, heightened autophagy activity diminishes sensitivity to PI treatment.Elevated CRIP1 levels serve as a biomarker for relapsed/refractory MM and correlate with shorter overall patient survival. To further comprehend the role of CRIP1 in multiple myeloma pathogenesis, we conducted transcriptome sequencing.

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Systems medicine dissection of chromosome 1q amplification reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma

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