2. Academic Validation
  3. ACSL4: a Double-edged Sword Target in Multiple Myeloma, Promotes Cell Proliferation and Sensitizes Cell to Ferroptosis

ACSL4: a Double-edged Sword Target in Multiple Myeloma, Promotes Cell Proliferation and Sensitizes Cell to Ferroptosis

  • Carcinogenesis. 2023 Mar 31;bgad015. doi: 10.1093/carcin/bgad015.
Jiasi Zhang 1,  Yuxi Liu 1,  Qun Li 1,  Liping Zuo 1,  Bo Zhang 1,  Fei Zhao 1,  Fengjuan Fan 1,  Shanshan Luo 1,  Yu Hu 1 2,  Chunyan Sun 1 2
Affiliations

Affiliations

  • 1 Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Dadao, Wuhan 430022, China.
  • 2 Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, China.
PMID: 36999754 DOI: 10.1093/carcin/bgad015
Abstract

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.

Keywords

Acyl-CoA synthetase long-chain family member 4; Ferroptosis; Lipogenesis; Multiple myeloma; c-Myc.

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