ACSL4: a Double-edged Sword Target in Multiple Myeloma, Promotes Cell Proliferation and Sensitizes Cell to Ferroptosis.
Jiasi ZhangYuxi LiuQun LiLiping ZuoBo ZhangFei ZhaoFengjuan FanShanshan LuoYu HuChunyan SunPublished in: Carcinogenesis (2023)
Overactive fatty acid metabolism is usually found in hematological malignancies including multiple myeloma (MM), but the underlying mechanisms remain unclear. Here, we reveal that acyl-CoA synthetase long-chain family member 4 (ACSL4) is abnormally over-expressed in MM cell lines and MM patients compared to healthy donors. Knockdown of ACSL4 inhibited MM cell proliferation and reduced fatty acid levels possibly by regulating lipid metabolism genes including c-Myc and sterol regulatory element binding proteins (SREBPs). As a propellent in ferroptosis, ACSL4 also determines the sensitivity of MM cells to ferroptosis inducer RSL3. Knockdown of ACSL4 rendered MM cells resistance to ferroptosis. Our findings suggest that ACSL4 is a double-edged sword target in MM. Based on the high expression of ACSL4, ferroptosis induction represents a promising therapeutic strategy for MM.
Keyphrases
- fatty acid
- cell death
- cell proliferation
- induced apoptosis
- cell cycle arrest
- multiple myeloma
- end stage renal disease
- chronic kidney disease
- single cell
- newly diagnosed
- stem cells
- endoplasmic reticulum stress
- transcription factor
- signaling pathway
- ejection fraction
- gene expression
- prognostic factors
- pi k akt
- binding protein
- bone marrow
- oxidative stress
- cell therapy
- dna methylation
- long non coding rna