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Proteomic analysis of ferroptosis pathways reveals a role of CEPT1 in suppressing ferroptosis

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Protein & Cell 2024年第9期15卷 686-703页

作者： Xiaoguang Liu Zhen Chen Yuelong Yan Fereshteh Zandkarimi Litong Nie Qidong Li Amber Horbath Kellen Olszewski Lavanya Kondiparthi Chao Mao Hyemin Lee Li Zhuang Masha Poyurovsky Brent RStockwell Junjie Chen boyi gan Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Biological Sciences and Department of Chemistry Columbia UniversityNew YorkNY 10027USA Kadmon Corporation LLC(A Sanofi Company)New YorkNY 10016USA The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences HoustonTX 77030USA The Barer Institute PhiladelphiaPA 19104USA

Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular *** this study,we established a protein interaction landscape for ferroptosis pathways through proteomic analyses,and identified choline/ethanolamine phosphotransferase 1(CEPT1)as a lysophosphatidylcholine acyltransferase 3(LPCAT3)-interacting protein that regulates LPCAT3 protein *** contrast to its known role in promoting phospholipid synthesis,we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid(PUFA)-containing ***,our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.

关键词： proteomics ferroptosis CEPT1 LPCAT3

How erastin assassinates cells by ferroptosis revealed

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Protein & Cell 2023年第2期14卷 84-86页

作者： boyi gan Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

Ferroptosis represents an oxidative form of iron-dependent cell death resulting from unrestrained peroxidized phospholipids on cellular membranes(Jiang et al.,2021).In recent years,research interest in ferroptosis has increased steeply partly due to its high relevance to diverse diseases(such as cancer and neurodegener-ative diseases)and the enormous potential of ferroptosis induc-ers and inhibitors to treat these diseases(Jiang et al.,2021;Tang et al.,2021.

关键词： diseases death

ACSL4,PUFA,and ferroptosis:new arsenal in anti-tumor immunity

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1363-1365页

作者： boyi gan Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA

In a recent study published in Cancer Cell,Liao et al.1 identified CD8+T-cell-derived interferon(IFN)γin combination with polyunsaturated fatty acids(PUFAs)as a natural ferroptosis inducer(FIN)to trigger tumor ferroptosis and promote anti-tumor immunity in an acyl-coenzyme A synthetase long-chain family member 4(ACSL4)-dependent *** refers to a form of regulated cell death triggered by excessive iron-dependent peroxidation of PUFA-containing phospholipids(PUFA-PLs)in the cellular membrane.

关键词： immunity peroxidation

Cystine transporter SLC7A11/xCT in cancer:ferroptosis,nutrient dependency,and cancer therapy

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Protein & Cell 2021年第8期12卷 599-620页

作者： Pranavi Koppula Li Zhuang boyi gan Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences HoustonTXUSA

The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human *** studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis,a form of regulated cell death induced by excessive lipid ***,cancer cells with high expression of SLC7A11(SLC7A11^(high))also have to endure the significant cost associated with SLC7A11-mediated metabolic reprogramming,leading to glucose-and glutamine-dependency in SLC7A11^(high) cancer cells,which presents potential metabolic vulnerabilities for therapeutic targeting in SLC7A11^(high) *** this review,we summarize diverse regulatory mechanisms of SLC7A11 in cancer,discuss ferroptosis-dependent and-independent functions of SLC7A11 in promoting tumor development,explore the mechanistic basis of SLC7A11-induced nutrient dependency in cancer cells,and conceptualize therapeutic strategies to target SLC7A11 in cancer *** review will provide the foundation for further understanding SLC7A11 in ferroptosis,nutrient dependency,and tumor biology and for developing novel effective cancer therapies.

关键词： SLC7A11 xCT cystine cysteine ferroptosis nutrient dependency cancer therapy

Ether phospholipids govern ferroptosis

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Journal of Genetics and Genomics 2021年第7期48卷 517-519页

作者： Hyemin Lee Li Zhuang boyi gan Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences HoustonTXUSA

Ferroptosis is a cell death modality triggered by excessive lipid *** recent studies(Zou et al.,2020;Cui et al.,2021)not only reveal critical roles of ether-linked phospholipids as an additional source for providing polyunsaturated fatty acid-containing phospholipids in driving ferroptosis but also suggest a context-dependent role of TMEM189-mediated vinyl-ether phospholipid(plasmalogen)synthesis in ferroptosis.

关键词： Ferroptosis Lipid peroxidation Ether phospholipids Plasmalogen TMEM189

Cytochrome P450 reductase(POR)as a ferroptosis fuel

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Protein & Cell 2021年第9期12卷 675-679页

Oxygen,iron,and polyunsaturated fatty acids(PUFAs;fatty acids containing more than one double bond)are all beneficial to our cellular *** of these components into cellular processes,however,comes at a cost:the bis-allylic structure of PUFAs and the enrichment of cellular environments with iron and oxygen render PUFA-containing phospholipids(PUFA-PLs)particularly susceptible to peroxidation(Yang and Stockwell,2016).

关键词： render Oxygen structure

Uncovering the IL-1β-PCAF-NNT axis:A new player in ferroptosis and tumor immune evasion

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Cancer Communications 2023年第9期43卷 1048-1050页

作者： Qidong Li boyi gan Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences HoustonTXUSA

Chronic inflammation is recognized as a crucial hallmark of ***-1β(IL-1β),one of the proinflammatory cytokines,plays an ambiguous or even contradictory role in cancer development[1].While increased expression of IL-1βin the tumor microenvironment is associated with tumor development,and invasiveness[1],it has also shown anti-tumorigenic effects in other contexts[2].Therefore,it is difficult to define IL-1β’s role as either tumor-promoting or anti-tumorigenic in *** investigation of IL-1βin specific contexts is essential to comprehensively understand its role in cancers.

关键词： tumor inflammation Interleukin

Ferroptosis,radiotherapy,and combination therapeutic strategies

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Protein & Cell 2021年第11期12卷 836-857页

作者： Guang Lei Chao Mao Yuelong Yan Li Zhuang boyi gan Department of Radiation Oncology Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences HoustonTXUSA

Ferroptosis,an iron-dependent form of regulated cell death driven by peroxidative damages of polyunsatu-rated-fatty-acid-containing phospholipids in cellular membranes,has recently been revealed to play an important role in radiotherapy-induced cell death and tumor suppression,and to mediate the synergy between radiotherapy and *** this review,we summarize known as well as putative mechanisms underlying the crosstalk between radiotherapy and fer-roptosis,discuss the interactions between ferroptosis and other forms of regulated cell death induced by radiotherapy,and explore combination therapeutic strategies targeting ferroptosis in radiotherapy and *** review will provide important frameworks for future investigations of ferroptosis in cancer therapy.

关键词： ferroptosis lipid peroxidation GPX4 SLC7A11 radiotherapy immunotherapy radiosensitization combination therapy

Hyperoxidized PRDX3 as a specific ferroptosis marker

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Life Metabolism 2023年第6期2卷 6-8页

作者： Yuelong Yan boyi gan Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences HoustonTX 77030United States

The lack of a reliable and specific marker for ferroptosis has hindered the advancement of treatments related to this cell death mechanism toward clinical application.A recent study published in Molecular Cell has identified hyperoxidized perox-iredoxin 3(PRDX3)as a promising marker for ferroptosis,open-ing up new avenues for monitoring and targeting ferroptosis in disease treatment.

关键词： oxidized clinical death