铁死亡在肿瘤中的研究进展
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摘要
铁死亡是近几年发现的不同于坏死和凋亡的一种新的程序性细胞死亡方式。其特征是铁依赖的脂质过氧化物积累到致死水平。铁死亡参与肝癌、胰腺癌、前列腺癌和乳腺癌等多种肿瘤的发生发展过程。SLC7A11和GPX4是铁死亡关键的调控基因,p53和BECN1等分子通过调控SLC7A11和GPX4参与铁死亡的调控。诱导肿瘤细胞铁死亡有望成为抗肿瘤治疗的新策略。
Ferroptosis, which is different from necrosis and apoptosis is a newly discovered programmed cell death. The characteristic of ferroptosis is the iron-dependent accumulation of lipid hydroperoxides up to lethal levels. Ferroptosis is involved in the formation and development of different cancers such as hepatocellular cancer, pancreatic cancer, prostate cancer and breast cancer. SLC7A11 and GPX4 are the key regulators in ferroptosis; p53 and BECN1 are involved in the ferroptosis via regulating SLC7A11 and GPX4; Inducing ferroptosis is a potential antitumor pathway.
Ferroptosis, which is different from necrosis and apoptosis is a newly discovered programmed cell death. The characteristic of ferroptosis is the iron-dependent accumulation of lipid hydroperoxides up to lethal levels. Ferroptosis is involved in the formation and development of different cancers such as hepatocellular cancer, pancreatic cancer, prostate cancer and breast cancer. SLC7A11 and GPX4 are the key regulators in ferroptosis; p53 and BECN1 are involved in the ferroptosis via regulating SLC7A11 and GPX4; Inducing ferroptosis is a potential antitumor pathway.
引文
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[23] Wang Z,Ding Y,Wang X,et al.Pseudolaric acid B triggers ferroptosis in glioma cells via activation of Nox4 and inhibition of xCT[J].Cancer Lett,2018,428:21-33.
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[2] Koppula P,Zhang Y,Zhuang L,et al.Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer[J].Cancer Commun,2018,38:12-26.
[3] Koppula P,Zhang Y,Shi J,et al.The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate[J].J Biol Chem.2017,292:14240-14249.
[4] 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,2018,40:2363-2370.
[5] Chen D,Tavana O,Chu B,et al.NRF2 is a major target of ARF in p53-Independent tumor suppression[J].Mol Cell,2017,68(1):224-232.
[6] Song X,Zhu S,Chen P,et al.AMPK-Mediated BECN1 phosphorylation promotes perroptosis by directly blocking system Xc(-) activity[J].CurrBiol,2018,28:2388-2399 e5.
[7] Kang R,Zhu S,Zeh HJ,et al.BECN1 is a new driver of ferroptosis[J].Autophagy,2018,14:2173-2175
[8] Rohr-Udilova N,Bauer E,Timelthaler G,et al.Impact of glutathione peroxidase 4 on cell proliferation,angiogenesis and cytokine production in hepatocellular carcinoma[J].Oncotarget,2018,9:10054-10068.
[9] Kinowaki Y,Curate M,Ishibashi S,et al.Glutathione peroxidase 4 overexpression inhibits ROS-induced cell death in diffuse large B-cell lymphoma[J].Lab Invest,2018,98:609-619.
[10] Yang W,Sriramaratnam R,Welsch M,et al.Regulation of ferroptotic cancer cell death by GPX4[J].Cell,2014,156:317-331.
[11] Alvarez SW,Sviderskiy VO,Terzi EM,et al.NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis[J].Nature,2017,551:639-643.
[12] Brown CW,Amante JJ,Goel HL,et al.The α6β4 integrin promotes resistance to ferroptosis[J].J Cell Biol,2017,216:4287-4297.
[13] Brown CW,Amante JJ,Mercurio AM.Cell clustering mediated by the adhesion protein PVRL4 is necessary for α6β4 integrin-promoted ferroptosis resistance in matrix-detached cells[J].J Biol Chem,2018,293:12741-12748.
[14] Chen MS,Wang SF,Hsu CY,et al.CHAC1 degradation of glutathione enhances cystine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells via the GCN2-eIF2α-ATF4 pathway[J].Oncotarget,2017,8:114588-114602.
[15] Sun X,Ou Z,Chen R,et al.Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells[J].Hepatology,2016,63:173-1784.
[16] Lemasters JJ.Evolution of voltage-dependent anion channel function:from molecular sieve to governator to actuator of ferroptosis[J].Front Oncol,2017,7:303-334.
[17] Shintoku R,Takigawa Y,Yamada K,et al.Lipoxy-genase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3[J].Cancer Sci,2017,108:2187-2194.
[18] Sato M,Kusumi R,Hamashima S,et al.The ferroptosis inducer erastin irreversibly inhibits system xc-and synergizes with cisplatin to increase cisplatin's cytotoxicity in cancer cells[J].Sci Rep,2018,8:968-982.
[19] Roh JL,Kim EH,Jang HJ,et al.Induction of ferroptotic cell death for overcoming cisplatin resistance of head and neck cancer.[J].Cancer Lett,2016,381:96-103.
[20] Hao S,Yu J,He W,et al.Cysteine dioxygenase 1 mediates erastin-Induced ferroptosis in human gastric cancer cells[J].Neoplasia,2017,19:1022-1032.
[21] Jelinek A,Heyder L,Daude M,et al.Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis[J].Free Radic Biol Med,2018,117:45-57.
[22] Gaschler MM,Andia AA,Liu H,et al.FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation[J].Nat Chem Biol,2018,1 4:507-515.
[23] Wang Z,Ding Y,Wang X,et al.Pseudolaric acid B triggers ferroptosis in glioma cells via activation of Nox4 and inhibition of xCT[J].Cancer Lett,2018,428:21-33.
[24] Lee YS,Lee DH,Jeong S Y,et al.Ferroptosis-inducing agents enhance TRAIL-induced apoptosis through upregulation of death receptor 5[J].J Cell Biochem,2018,120:928-939.