Research progress of sphingolipid metabolism and ferroptosis in liver
cancer

doi:10.3760/cma.j.issn.1007-1245.2022.21.009

International Medicine and Health Guidance News ›› 2022, Vol. 28 ›› Issue (21): 3004-3008.DOI: 10.3760/cma.j.issn.1007-1245.2022.21.009

• Scientific Research • Previous Articles Next Articles

Research progress of sphingolipid metabolism and ferroptosis in liver cancer

Wang Junnan^1,4, Jin Junfei^1,2,3,4

¹Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Affiliated Hospital of Guilin Medical University, Guilin 541001, China; ²Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, Affiliated Hospital of Guilin Medical University, Guilin 541001, China; ³China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin 541001, China; ⁴Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, China

Received:2022-08-06 Online:2022-11-01 Published:2022-11-16
Contact: Jin Junfei, Email: changliangzijin@163.com
Supported by:
Project of National Natural Science Foundation (81960520); Key Project of Natural Science Foundation of Guangxi (2020GXNSFDA238006); Project Supported by Special Fund of the Central Government Guiding Local Scientific and Technological Development by Guangxi Science and Technology Department (ZY21195024); Project Supported by Guangxi Distinguished Expert Special Fund (2019B12); Project Supported by "139" Medical High Level Talents Training Plan in Guangxi (G202002005); Construction Fund of Guangxi Health Commission's Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases (ZJC2020005); Construction Fund of Key Disciplines of Medical and Health in Guangxi (2021-8-4-3); Science and Technology Planned Project in Guilin (20210102-1)

神经鞘脂代谢与铁死亡在肝癌中的研究进展

王俊楠^1,4 金俊飞^1,2,3,4

¹桂林医学院附属医院广西肝脏损伤与修复分子医学重点实验室，桂林　541001；²桂林医学院附属医院广西神经鞘脂代谢相关疾病基础研究重点实验室，桂林　541001；³桂林医学院中美健康与疾病脂质研究中心，桂林　541001；⁴桂林医学院附属医院肝胆胰外科实验室，桂林　541001

通讯作者: 金俊飞，Email：changliangzijin@163.com
基金资助:
国家自然科学基金项目（81960520）；广西自然科学基金重点项目（2020GXNSFDA238006）；广西科技厅中央引导地方科技发展资金项目（ZY21195024）；“广西特聘专家”专项经费资助项目（2019B12）；广西医学高层次骨干人才“139”计划资助项目（G202002005）；广西壮族自治区卫生健康委员会广西神经鞘脂代谢相关疾病基础研究重点实验室建设经费（ZJC2020005）；广西医疗卫生重点学科建设经费（2021-8-4-3）；桂林市科学研究与技术开发计划项目（20210102-1）

Abstract

Abstract: Ferroptosis is a cell death mode different from apoptosis. Recent studies have found that ferroptosis involves in the treatment and drug resistance of liver cancer. A large number of studies have confirmed that sphingolipid metabolism is closely related to the occurrence and development of liver cancer. There is interaction between sphingolipid metabolism pathway and ferroptosis pathway, and both are closely related to liver cancer. This article reviews the recent research progress on the interaction between sphingolipid metabolism pathway and ferroptosis pathway and its influence on the occurrence, development, and treatment of liver cancer.

Key words: Ferroptosis, Sphingolipid metabolism, Liver cancer

摘要： 铁死亡（ferroptosis）是不同于凋亡的一种细胞死亡方式，最新研究发现在肝癌治疗以及肝癌耐药等过程铁死亡参与其中。大量研究证实神经鞘脂代谢和肝癌发生、发展密切相关。神经鞘脂代谢通路和铁死亡通路存在交互作用，两者都与肝癌密切相关。本文就神经鞘脂代谢通路与铁死亡通路的交互作用以及对肝癌发生、发展、治疗等方面影响的近期研究进展进行阐述。

关键词: 铁死亡, 鞘脂代谢, 肝癌

Wang Junnan, Jin Junfei. Research progress of sphingolipid metabolism and ferroptosis in liver cancer [J]. International Medicine and Health Guidance News, 2022, 28(21): 3004-3008.

王俊楠金俊飞. 神经鞘脂代谢与铁死亡在肝癌中的研究进展[J]. 国际医药卫生导报, 2022, 28(21): 3004-3008.

References

[1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
[2] Hannun YA, Loomis CR, Merrill AH, et al. Sphingosine inhibition of protein kinase C activity and of phorbol dibutyrate binding in vitro and in human platelets [J]. J Biol Chem, 1986, 261(27):12604-12609.
[3] Raichur S. Ceramide synthases are attractive drug targets for treating metabolic diseases [J]. Front Endocrinol (Lausanne), 2020, 11:483. DOI: 10.3389/fendo. 2020. 00483.
[4] Lei G, Zhuang L, Gan B. Targeting ferroptosis as a vulnerability in cancer [J]. Nat Rev Cancer, 2022, 22(7):381-396. DOI: 10.1038/s41568-022-00459-0.
[5] Doll S, Proneth B, Tyurina YY, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition [J]. Nat Chem Biol, 2017, 13(1):91-98. DOI: 10.1038/nchembio.2239.
[6] Kuhn H, Saam J, Eibach S, et al. Structural biology of mammalian lipoxygenases: enzymatic consequences of targeted alterations of the protein structure [J]. Biochem Biophys Res Commun, 2005, 338(1):93-101. DOI: 10.1016/j.bbrc.2005.08.238.
[7] Kuhn H, Saam J, Eibach S, et al. Structural biology of mammalian lipoxygenases: enzymatic consequences of targeted alterations of the protein structure [J]. Biochem Biophys Res Commun, 2005, 338(1): 93-101. DOI: 10.1016/j.bbrc.2005.08.238.
[8] Magtanong L, Ko PJ, To M, et al. Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state [J]. Cell Chem Biol, 2019, 26(3): 420-432.e9. DOI: 10.1016/j.chembiol.2018.11.016.
[9] Mumbauer S, Pascual J, Kolotuev I, et al. Ferritin heavy chain protects the developing wing from reactive oxygen species and ferroptosis [J]. PLoS Genet, 2019, 15(9): e1008396. DOI: 10.1371/journal.pgen.1008396.
[10] Gao M, Monian P, Pan Q, et al. Ferroptosis is an autophagic cell death process [J]. Cell Res, 2016, 26(9): 1021-1032. DOI: 10.1038/cr.2016.95.
[11] Hou W, Xie Y, Song X, et al. Autophagy promotes ferroptosis by degradation of ferritin [J]. Autophagy, 2016, 12(8): 1425-1428. DOI: 10.1080/15548627. 2016.1187366.
[12] 吴威,谭永星,王永旺. 肝移植围术期诱发肠损伤铁死亡的研究新进展[J]. 国际医药卫生导报,2022,28(7):1025-1028. DOI:10.3760/cma.j.issn.1007-1245.2022. 07.034.
[13] 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. DOI: 10.1038/s41586-019-1705-2.
[14] 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.DOI: 10.1038/s41586-021- 03539-7.
[15] Hu Q, Wei W, Wu D, et al. Blockade of GCH1/BH4 axis activates ferritinophagy to mitigate the resistance of colorectal cancer to erastin-induced ferroptosis[J]. Front Cell Dev Biol, 2022, 10: 810327.DOI: 10.3389/fcell.2022. 810327.
[16] Ogretmen B. Sphingolipids in cancer: regulation of pathogenesis and therapy[J]. FEBS Lett, 2006, 580(23): 5467-5476.DOI: 10.1016/j.febslet.2006.08.052.
[17] Krautbauer S, Meier EM, Rein-Fischboeck L, et al. Ceramide and polyunsaturated phospholipids are strongly reduced in human hepatocellular carcinoma[J]. Biochim Biophys Acta, 2016, 1861(11): 1767-1774.DOI: 10.1016/j.bbalip.2016.08.014.
[18] Funaki M, Kitabayashi J, Shimakami T, et al. Peretinoin, an acyclic retinoid, inhibits hepatocarcinogenesis by suppressing sphingosine kinase 1 expression in vitro and in vivo[J]. Sci Rep, 2017, 7(1): 16978. DOI: 10.1038/s41598-017-17285-2.
[19] Miura K, Nagahashi M, Prasoon P, et al. Dysregulation of sphingolipid metabolic enzymes leads to high levels of sphingosine-1-phosphate and ceramide in human hepatocellular carcinoma[J]. Hepatol Res, 2021, 51(5): 614-626. DOI: 10.1111/hepr.13625.
[20] Matsushima-Nishiwaki R, Yamada N, Fukuchi K, et al. Sphingosine 1-phosphate (S1P) reduces hepatocyte growth factor-induced migration of hepatocellular carcinoma cells via S1P receptor 2[J]. PLoS One, 2018, 13(12): e0209050. DOI: 10.1371/journal.pone.0209050.
[21] Sun X, Niu X, Chen R, et al. Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis[J]. Hepatology, 2016, 64(2): 488-500. DOI: 10.1002/hep.28574.
[22] Gao R, Kalathur RKR, Coto-Llerena M, et al. YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis [J]. EMBO Mol Med, 2021, 13(12): e14351.DOI: 10.15252/emmm.202114351.
[23] 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. DOI: 10.1002/hep.28251.
[24] Thayyullathil F, Rahman A, Pallichankandy S, et al. ROS-dependent prostate apoptosis response-4 (Par-4) up-regulation and ceramide generation are the prime signaling events associated with curcumin-induced autophagic cell death in human malignant glioma [J]. FEBS Open Bio, 2014, 4: 763-776.DOI: 10.1016/j.fob.2014.08.005.
[25] Yang WS, Kim KJ, Gaschler MM, et al. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis[J]. Proc Natl Acad Sci U S A, 2016, 113(34): E4966-E4975. DOI: 10.1073/pnas.1603244113.
[26] Thayyullathil F, Cheratta AR, Alakkal A, et al. Acid sphingomyelinase-dependent autophagic degradation of GPX4 is critical for the execution of ferroptosis [J]. Cell Death Dis, 2021, 12(1): 26. DOI: 10.1038/s41419-020-03297-w.
[27] Niu B, Lei X, Xu Q, et al. Protecting mitochondria via inhibiting VDAC1 oligomerization alleviates ferroptosis in acetaminophen-induced acute liver injury [J]. Cell Biol Toxicol, 2022, 38(3): 505-530. DOI: 10.1007/s10565- 021-09624-x.
[28] Lin M, Liao W, Dong M, et al. Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide[J]. Febs j, 2018, 285(20): 3835-3848. DOI: 10.1111/febs. 14635.
[29] Schissel SL, Keesler GA, Schuchman EH, et al. The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene[J]. J Biol Chem, 1998, 273(29): 18250-18259. DOI: 10.1074/jbc.273.29.18250.
[30] Diao X, Cui Q, Tian N, et al. Hemorrhage-induced sphingosine kinase 1 contributes to ferroptosis-mediated secondary brain injury in intracerebral hemorrhage[J]. Mol Neurobiol, 2022, 59(3): 1381-1397. DOI: 10.1007/s12035-021-02605-5.

Research progress of sphingolipid metabolism and ferroptosis in liver cancer

神经鞘脂代谢与铁死亡在肝癌中的研究进展

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