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Commentary

Research progress on ferroptosis mechanism and osteosarcoma

  • LIANG Tao ,
  • LIU Zhuochao ,
  • ZHANG Weibin
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  • Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received date: 2025-01-23

Abstract

Osteosarcoma is the most common primary bone tumor in children and adolescents, with a high degree of malignancy and a poor prognosis. The prevailing treatment paradigm continues to be based on a multimodality therapy of neoadjuvant chemotherapy-surgery-adjuvant chemotherapy, but the survival benefit provided by chemotherapy has remained relatively constant over the past 40 years. Ferroptosis, as a newly discovered form of cell death, has seen rapid research progress over the past decade, and targets for tumor treatment are constantly discovered. Thus, this article commenced with the proposal, developmental nodes, and underlying mechanisms of ferroptosis, then summarized the research results on ferroptosis in osteosarcoma, anticipated its developmental prospects, and highlighted the most urgent things in this field.

Cite this article

LIANG Tao , LIU Zhuochao , ZHANG Weibin . Research progress on ferroptosis mechanism and osteosarcoma[J]. Surgical Research and New Technique, 2025 , 14(1) : 1 -8 . DOI: 10.3969/j.issn.2095-378X.2025.01.001

References

[1] Sun X, Ou Z, Chen R, et al.Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells[J]. Hepatology, 2016, 63(1): 173-184.
[2] Dolma S, Lessnick SL, Hahn WC, et al.Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells[J]. Cancer Cell, 2003, 3(3): 285-296.
[3] Seiler A, Schneider M, Förster H, et al.Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death[J]. Cell Metab, 2008, 8(3): 237-248.
[4] Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4[J]. Cell, 2014, 156(1-2): 317-331.
[5] Jiang L, Kon N, Li T, et al.Ferroptosis as a p53-mediated activity during tumour suppression[J]. Nature, 2015,520(7545): 57-62.
[6] Sun WY, Wang R, He RR.LC-MS-based redox phosphoipidomics analysis in ferroptosis[J]. Methods Mol Biol, 2023, 2712: 81-90.
[7] Qiu B, Zandkarimi F, Bezjian CT, et al.Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis[J]. Cell, 2024, 187(5): 1177-1190.
[8] Yang WS, Stockwell BR.Ferroptosis: death by lipid peroxidation[J]. Trends Cell Biol, 2016, 26(3): 165-176.
[9] Bersuker K, Hendricks JM, Li Z, et al.The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis[J]. Nature, 2019, 575(7784): 688-692.
[10] Ding CC, Rose J, Sun T, et al.MESH1 is a cytosolic NADPH phosphatase that regulates ferroptosis[J]. Nat Metab, 2020, 2(3): 270-277.
[11] Mao C, Liu X, Zhang Y, et al.DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer[J]. Nature, 2021, 593(7860): 586-590.
[12] Kraft VAN, Bezjian CT, Pfeiffer S, et al.GTP cyclohydrolase 1/tetrahydrobiopterin counteract ferroptosis through lipid remodeling[J]. ACS Cent Sci, 2020, 6(1): 41-53.
[13] Lee J, You JH, Roh JL.Poly(rC)-binding protein 1 represses ferritinophagy-mediated ferroptosis in head and neck cancer[J]. Redox Biol, 2022, 51: 102276.
[14] Wenzel SE, Tyurina YY, Zhao J, et al.PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals[J]. Cell, 2017, 171(3): 628-641.
[15] Manivarma T, Kapralov AA, Samovich SN, et al.Membrane regulation of 15LOX-1/PEBP1 complex prompts the generation of ferroptotic signals, oxygenated PEs[J]. Free Radic Biol Med, 2023, 208: 458-467.
[16] Zou Y, Li H, Graham ET, et al.Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis[J].Nat Chem Biol, 2021, 17(4): 501.
[17] Polewski MD, Reveron-Thornton RF, Cherryholmes GA, et al.Increased expression of system xc- in glioblastoma confers an altered metabolic state and temozolomide resistance[J]. Mol Cancer Res, 2016, 14(12): 1229-1242.
[18] Polewski MD, Reveron-Thornton RF, Cherryholmes GA, et al.SLC7A11 overexpression in glioblastoma is associated with increased cancer stem cell-like properties[J]. Stem Cells, 2017, 26(17): 1236-1246.
[19] Yang X, Liu J, Wang C, et al.miR-18a promotes glioblastoma development by down-regulating ALOXE3-mediated ferroptotic and anti-migration activities[J]. Oncogenesis, 2021, 10(2): 15.
[20] Huang C, Yang M, Deng J,et al.Upregulation and activation of p53 by erastin-induced reactive oxygen species contribute to cytotoxic and cytostatic effects in A549 lung cancer cells[J]. Oncol Rep, 2018, 40(4): 2363-2370.
[21] Hu K, Li K, Lv J, et al.Suppression of the SLC7A11/glutathione axis causes synthetic lethality in KRAS-mutant lung adenocarcinoma[J]. J Clin Invest, 2020, 130(4): 1752-1766.
[22] Ma Z, Zhang H, Lian M, et al.SLC7A11, a component of cysteine/glutamate transporter, is a novel biomarker for the diagnosis and prognosis in laryngeal squamous cell carcinoma[J]. Oncol Rep, 2017, 38(5): 3019-3029.
[23] Egolf S, Zou J, Anderson A, et al. MLL4 mediates differentiation and tumor suppression through ferroptosis[J]. Sci Adv, 2021, 7(50): eabj9141.
[24] Tang R, Hua J, Xu J, et al.The role of ferroptosis regulators in the prognosis, immune activity and gemcitabine resistance of pancreatic cancer[J]. Ann Transl Med, 2020, 8(21): 1347.
[25] Bolli E, O'Rourke JP, Conti L, et al. A virus-like-particle immunotherapy targeting epitope-specific anti-xCT expressed on cancer stem cell inhibits the progression of metastatic cancer in vivo[J]. Oncoimmunology, 2017, 7(3): e1408746.
[26] Liao P, Wang W, Wang W, et al.CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4[J]. Cancer Cell, 2022, 40(4): 365-378.
[27] Ubellacker JM, Tasdogan A, Ramesh V, et al.Lymph protects metastasizing melanoma cells from ferroptosis[J]. Nature, 2020, 585(7823): 113-118.
[28] Lin H, Tison K, Du Y, et al.Itaconate transporter SLC13A3 impairs tumor immunity via endowing ferroptosis resistance[J]. Cancer Cell, 2024, 42(12): 2032-2044.
[29] Lv H, Zhen C, Liu J,et al.β-Phenethyl isothiocyanate induces cell death in human osteosarcoma through altering iron metabolism, disturbing the redox balance, and activating the MAPK signaling pathway[J]. Oxid Med Cell Longev, 2020,2020: 5021983.
[30] Jiwa H, Xie Z, Qu X, et al.Casticin induces ferroptosis in human osteosarcoma cells through Fe2+ overload and ROS production mediated by HMOX1 and LC3-NCOA4[J]. Biochem Pharmacol, 2024, 226: 116346.
[31] Chen W, Li Z, Yu N, et al.Bone-targeting exosome nanoparticles activate Keap1 / Nrf2 / GPX4 signaling pathway to induce ferroptosis in osteosarcoma cells[J]. J Nanobiotechnology, 2023, 21(1): 355.
[32] Zeng X, Lin GX, Zeng X, et al.Penfluridol regulates p62 / Keap1 /Nrf2 signaling pathway to induce ferroptosis in osteosarcoma cells[J]. Biomed Pharmacother, 2024, 177: 117094.
[33] Luo Y, Gao X, Zou L, et al.Bavachin induces ferroptosis through the STAT3/P53/SLC7A11 axis in osteosarcoma cells[J]. Oxid Med Cell Longev, 2021, 2021: 1783485.
[34] Li X, Liu J.FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma[J]. BMC Cancer, 2023, 23(1): 179.
[35] Panczyszyn E, Saverio V, Monzani R, et al.FSP1 is a predictive biomarker of osteosarcoma cells' susceptibility to ferroptotic cell death and a potential therapeutic target[J]. Cell Death Discov, 2024, 10(1): 87.
[36] Yuan Y, Mei Z, Qu Z, et al.Exosomes secreted from cardiomyocytes suppress the sensitivity of tumor ferroptosis in ischemic heart failure[J]. Signal Transduct Target Ther, 2023,8(1): 121.
[37] Luo SH, Tian JM, Chu Y, et al.The BRD4-SRPK2-SRSF2 signal modulates the splicing efficiency of ACSL3 pre-mRNA and influences erastin-induced ferroptosis in osteosarcoma cells[J]. Cell Death Dis, 2023, 14(11): 760.
[38] Yang L, Liu J, Liu S.Clinical significance and immune landscape of a novel ferroptosis-related prognosis signature in osteosarcoma[J]. BMC Cancer, 2023, 23(1): 229.
[39] Zhu Y, Yang L, Yu Y, et al.Hydroxysafflor yellow A induced ferroptosis of osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway[J]. Oncol Res, 2024, 32(5): 899-910.
[40] Xu WN, Yang RZ, Zheng HL,et al.NDUFA4L2 regulated by HIF-1α promotes metastasis and epithelial-mesenchymal transition of osteosarcoma cells through inhibiting ROS production[J]. Front Cell DevBiol, 2020, 8: 515051.
[41] Jiang M, Jike Y, Liu K, et al.Exosome-mediated miR-144-3p promotes ferroptosis to inhibit osteosarcoma proliferation, migration, and invasion through regulating ZEB1[J]. Mol Cancer. 2023, 22(1): 113.
[42] Ma J, Guo Z, Yang X, et al.Exploration of various roles of hypoxia genes in osteosarcoma[J]. Sci Rep, 2022, 12(1): 18293.
[43] Zheng D, Xia K, Wei Z, et al.Identification of a novel gene signature with regard to ferroptosis, prognosis prediction, and immune microenvironment in osteosarcoma[J]. Front Genet, 2022, 13: 944978.
[44] Lv Z, Yang D, Li J, et al.Bone morphogenetic protein 9 overexpression reduces osteosarcoma cell migration and invasion[J]. Mol Cells, 2013, 36(2): 119-126.
[45] Chen M, Jiang Y, Sun Y.KDM4A-mediated histone demethylation of SLC7A11 inhibits cell ferroptosis in osteosarcoma[J]. Biochem Biophys Res Commun, 2021, 550: 77-83.
[46] Meazza C, Scanagatta P.Metastatic osteosarcoma: a challenging multidisciplinary treatment[J]. Expert Rev Anticancer Ther, 2016, 16(5): 543-556.
[47] Wang D, Song Z, Wang Z.Common mechanism of pathogenesis in various types of metastatic osteosarcoma[J]. Oncol Lett, 2017, 14(5): 6307-6313.
[48] Zhan F, He T, Chen Z, et al.RhoA enhances osteosarcoma resistance to MPPa-PDT via the Hippo/YAP signaling pathway[J]. Cell Biosci,2021, 11(1): 179.
[49] Zhan F, Zhang Y, Zuo Q, et al.YAP knockdown in combination with ferroptosis induction increases the sensitivity of HOS human osteosarcoma cells to pyropheophorbide-α methyl ester-mediated photodynamic therapy[J]. Photodiagnosis Photodyn Ther, 2022, 39: 102964.
[50] Fu J, Li T, Yang Y, et al.Activatable nanomedicine for overcoming hypoxia-induced resistance to chemotherapy and inhibiting tumor growth by inducing collaborative apoptosis and ferroptosis in solid tumors[J]. Biomaterials, 2021, 268: 120537.
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