脂质代谢在肺癌发生发展及诊疗领域中的研究进展

doi:10.3969/j.issn.1674-8115.2022.12.016

上海交通大学学报（医学版） ›› 2022, Vol. 42 ›› Issue (12): 1766-1771.doi: 10.3969/j.issn.1674-8115.2022.12.016

• 综述 • 上一篇

脂质代谢在肺癌发生发展及诊疗领域中的研究进展

胡婵婵¹^,²(), 范毅², 徐源¹^,³^,⁴, 胡志坚², 曾奕明¹^,³^,⁴()

^1.福建医科大学附属第二医院临床研究中心，泉州 362000
^2.福建医科大学公共卫生学院流行病与卫生统计学系，福州 350122
^3.福建医科大学附属第二医院呼吸与危重症医学科，泉州 362000
^4.福建省呼吸医学中心，泉州 362000

收稿日期:2022-07-06 接受日期:2022-12-18 出版日期:2022-12-28 发布日期:2022-12-28
通讯作者: 曾奕明 E-mail:hcc@fjmu.edu.cn;zeng_yi_ming@126.com
作者简介:胡婵婵（1996—），女，硕士生，电子信箱：hcc@fjmu.edu.cn。
基金资助:
福建省科技创新联合资金项目(2020Y9018);福建省自然科学基金(2021J01726);中央引导地方科技发展专项(2020L3009)

Lipid metabolism and lung cancer: emerging roles in occurrence, progression, diagnosis and treatment

HU Chanchan¹^,²(), FAN Yi², XU Yuan¹^,³^,⁴, HU Zhijian², ZENG Yiming¹^,³^,⁴()

^1.Clinical Research Centre, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China
^2.Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China
^3.Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China
^4.Respiratory Medicine Center of Fujian Province, Quanzhou 362000, China

Received:2022-07-06 Accepted:2022-12-18 Online:2022-12-28 Published:2022-12-28
Contact: ZENG Yiming E-mail:hcc@fjmu.edu.cn;zeng_yi_ming@126.com
Supported by:
Scientific and Technological Innovation Joint Capital Projects of Fujian Province(2020Y9018);Natural Science Foundation of Fujian Province(2021J01726);Central Government-Led Local Science and Technology Development Special Project(2020L3009)

摘要/Abstract

摘要：

肺癌是全球最严重的健康问题之一，准确诊断其严重程度和分期、评估治疗反应和预后、开发新的治疗策略至关重要。近年来，脂质组学成为研究热点，其聚焦于了解与疾病相关的脂质代谢、发现生物标志物和监测治疗策略的目标，为揭示肺癌的脂质谱和病理生理机制提供见解。脂质代谢紊乱是由肿瘤细胞内一些基因结构与功能改变引起的一系列脂质代谢异常，影响细胞周期、增殖、生长和分化等细胞功能，可导致癌变。此外，脂质代谢的特异性可以用来确定肺癌治疗的新代谢靶点。在临床上，降脂药物和抗脂质过氧化治疗效果显著。该文综述了脂质代谢在肺癌发生、发展及诊疗中的研究进展，重点总结了脂质代谢紊乱支持肺癌生长的机制以及脂质代谢的潜在靶点，探讨了靶向脂质代谢途径的肺癌治疗方法，并展望了肺癌脂质组学未来的发展前景和面对的挑战。

关键词: 肺癌, 脂质代谢紊乱, 机制, 治疗靶点

Abstract:

Lung cancer is one of the most serious health problems worldwide, and it is crucial to accurately diagnose its severity and staging, assess treatment response and prognosis, and develop new treatment strategies. In recent years, lipidomics has emerged as a new hotspot that focuses on understanding disease-related lipid metabolism, discovering biomarkers and monitoring targets for therapeutic strategies, and providing insights into the lipid profile and pathophysiological mechanisms of lung cancer. Disorders of lipid metabolism are a series of abnormalities in lipid metabolism caused by structural and functional alterations of some genes in tumor cells, which affect cellular functions such as cell cycle, proliferation, growth and differentiation, leading to carcinogenesis. In addition, the specificity of lipid metabolism can be used to identify new metabolic targets for lung cancer treatment, and in clinical practice, lipid-lowering drugs and anti-lipid peroxidation therapy are effective. This article reviews the latest research advances in lipid metabolism in the development, progression, diagnosis, and treatment of lung cancer, focusing on the novel mechanisms by which disorders of lipid metabolism support the growth of lung cancer and the potential targets of lipid metabolism, discusses therapeutic approaches to target lipid metabolic pathways in lung cancer, and presents the future prospects and challenges of lipidomics in lung cancer.

Key words: lung cancer, lipid metabolism disorders, mechanism, therapeutic target

中图分类号:

R734.2

胡婵婵, 范毅, 徐源, 胡志坚, 曾奕明. 脂质代谢在肺癌发生发展及诊疗领域中的研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(12): 1766-1771.

HU Chanchan, FAN Yi, XU Yuan, HU Zhijian, ZENG Yiming. Lipid metabolism and lung cancer: emerging roles in occurrence, progression, diagnosis and treatment[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(12): 1766-1771.

参考文献 54

1	SUNG H, FERLAY J, SIEGEL R L, 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.
2	ZHENG R, ZHANG S, ZENG H, et al. Cancer incidence and mortality in china, 2016[J]. J Natl Cancer Cent, 2022, 2(1): 1-9.
3	BUTLER L M, PERONE Y, DEHAIRS J, et al. Lipids and cancer: emerging roles in pathogenesis, diagnosis and therapeutic intervention[J]. Adv Drug Deliv Rev, 2020, 159: 245-293.
4	MIGITA T, NARITA T, NOMURA K, et al. Atp citrate lyase: activation and therapeutic implications in non-small cell lung cancer[J]. Cancer Res, 2008, 68(20): 8547-8554.
5	HANAI J, DORO N, SASAKI A T, et al. Inhibition of lung cancer growth: ATP citrate lyase knockdown and statin treatment leads to dual blockade of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/AKT pathways[J]. J Cell Physiol, 2012, 227(4): 1709-1720.
6	WANG C, MENG X, ZHOU Y, et al. Long noncoding RNA CTD-2245E15.3 promotes anabolic enzymes ACC₁ and PC to support non-small cell lung cancer growth[J]. Cancer Res, 2021, 81(13): 3509-3524.
7	SVENSSON R U, PARKER S J, EICHNER L J, et al. Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models[J]. Nat Med, 2016, 22(10): 1108-1119.
8	SCHCOLNIK-CABRERA A, CHÁVEZ-BLANCO A, DOMÍNGUEZ-GÓMEZ G, et al. Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy[J]. Expert Opin Investig Drugs, 2018, 27(5): 475-489.
9	CHANG L, FANG S, CHEN Y, et al. Inhibition of FASN suppresses the malignant biological behavior of non-small cell lung cancer cells via deregulating glucose metabolism and AKT/ERK pathway[J]. Lipids Health Dis, 2019, 18(1): 118.
10	SHIMANO H, SATO R. SREBP-regulated lipid metabolism: convergent physiology-divergent pathophysiology[J]. Nat Rev Endocrinol, 2017, 13(12): 710-730.
11	LEE G, ZHENG Y, CHO S, et al. Post-transcriptional regulation of de novo lipogenesis by mTORC1-S6K1-SRPK₂ signaling[J]. Cell, 2017, 171(7): 1545-1558.e18.
12	WANG J Q, WU Z X, YANG Y, et al. ATP-binding cassette (ABC) transporters in cancer: a review of recent updates[J]. J Evid Based Med, 2021, 14(3): 232-256.
13	JAROMI L, CSONGEI V, VESEL M, et al. KRAS and EGFR mutations differentially alter ABC drug transporter expression in cisplatin-resistant non-small cell lung cancer[J]. Int J Mol Sci, 2021, 22(10): 5384.
14	LI Z, KANG Y. Lipid metabolism fuels cancer's spread[J]. Cell Metab, 2017, 25(2): 228-230.
15	JIANG M, WU N, XU B, et al. Fatty acid-induced CD36 expression via O-GlcNAcylation drives gastric cancer metastasis[J]. Theranostics, 2019, 9(18): 5359-5373.
16	YANG S, KOBAYASHI S, SEKINO K, et al. Fatty acid-binding protein 5 controls lung tumor metastasis by regulating the maturation of natural killer cells in the lung[J]. FEBS Lett, 2021, 595(13): 1797-1805.
17	MA Y, TEMKIN S M, HAWKRIDGE A M, et al. Fatty acid oxidation: an emerging facet of metabolic transformation in cancer[J]. Cancer Lett, 2018, 435: 92-100.
18	QU Q, ZENG F, LIU X, et al. Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer[J]. Cell Death Dis, 2016, 7: e2226.
19	ZAUGG K, YAO Y, REILLY P T, et al. Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress[J]. Genes Dev, 2011, 25(10): 1041-1051.
20	FUJIWARA N, NAKAGAWA H, ENOOKU K, et al. CPT2 downregulation adapts HCC to lipid-rich environment and promotes carcinogenesis via acylcarnitine accumulation in obesity[J]. Gut, 2018, 67(8): 1493-1504.
21	WOHLHIETER C A, RICHARDS A L, UDDIN F, et al. Concurrent mutations in STK11 and KEAP1 promote ferroptosis protection and SCD1 dependence in lung cancer[J]. Cell Rep, 2020, 33(9): 108444.
22	HILVO M, DENKERT C, LEHTINEN L, et al. Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression[J]. Cancer Res, 2011, 71(9): 3236-3245.
23	NOTO A, DE VITIS C, PISANU M E, et al. Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ[J]. Oncogene, 2017, 36(32): 4573-4584.
24	CRUZ A L S, BARRETO E A, FAZOLINI N P B, et al. Lipid droplets: platforms with multiple functions in cancer hallmarks[J]. Cell Death Dis, 2020, 11(2): 105.
25	PETAN T, JARC E, JUSOVIĆ M. Lipid droplets in cancer: guardians of fat in a stressful world[J]. Molecules, 2018, 23(8): E1941.
26	VEGLIA F, TYURIN V A, MOHAMMADYANI D, et al. Lipid bodies containing oxidatively truncated lipids block antigen cross-presentation by dendritic cells in cancer[J]. Nat Commun, 2017, 8(1): 2122.
27	LETTIERO B, INASU M, KIMBUNG S, et al. Insensitivity to atorvastatin is associated with increased accumulation of intracellular lipid droplets and fatty acid metabolism in breast cancer cells[J]. Sci Rep, 2018, 8(1): 5462.
28	XU H, ZHOU S, TANG Q, et al. Cholesterol metabolism: new functions and therapeutic approaches in cancer[J]. Biochim Biophys Acta Rev Cancer, 2020, 1874(1): 188394.
29	MERINO SALVADOR M, GÓMEZ DE CEDRÓN M, MORENO RUBIO J, et al. Lipid metabolism and lung cancer[J]. Crit Rev Oncol Hematol, 2017, 112: 31-40.
30	WU Y, SI R, TANG H, et al. Cholesterol reduces the sensitivity to platinum-based chemotherapy via upregulating ABCG2 in lung adenocarcinoma[J]. Biochem Biophys Res Commun, 2015, 457(4): 614-620.
31	MARIEN E, MEISTER M, MULEY T, et al. Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles[J]. Int J Cancer, 2015, 137(7): 1539-1548.
32	WEI C, DONG X, LU H, et al. LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway[J]. J Exp Clin Cancer Res, 2019, 38(1): 95.
33	LI P, LU M, SHI J, et al. Lung mesenchymal cells elicit lipid storage in neutrophils that fuel breast cancer lung metastasis[J]. Nat Immunol, 2020, 21(11): 1444-1455.
34	TOMIN T, FRITZ K, GINDLHUBER J, et al. Deletion of adipose triglyceride lipase links triacylglycerol accumulation to a more-aggressive phenotype in a549 lung carcinoma cells[J]. J Proteome Res, 2018, 17(4): 1415-1425.
35	AL-ZOUGHBI W, PICHLER M, GORKIEWICZ G, et al. Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia[J]. Oncotarget, 2016, 7(23): 33832-33840.
36	HAN X. Lipidomics for studying metabolism[J]. Nat Rev Endocrinol, 2016, 12(11): 668-679.
37	CHENG C, RU P, GENG F, et al. Glucose-mediated N-glycosylation of SCAP is essential for SREBP-1 activation and tumor growth[J]. Cancer Cell, 2015, 28(5): 569-581.
38	MOLCKOVSKY A, SIU L L. First-in-class, first-in-human phase I results of targeted agents: highlights of the 2008 American society of clinical oncology meeting[J]. J Hematol Oncol, 2008, 1: 20.
39	WANG J, LI Y. CD36 tango in cancer: signaling pathways and functions[J]. Theranostics, 2019, 9(17): 4893-4908.
40	ZAIDI N, ROYAUX I, SWINNEN J V, et al. ATP citrate lyase knockdown induces growth arrest and apoptosis through different cell- and environment-dependent mechanisms[J]. Mol Cancer Ther, 2012, 11(9): 1925-1935.
41	HATZIVASSILIOU G, ZHAO F, BAUER D E, et al. ATP citrate lyase inhibition can suppress tumor cell growth[J]. Cancer Cell, 2005, 8(4): 311-321.
42	YANG L, ZHANG F, WANG X, et al. A FASN-TGF-β1-FASN regulatory loop contributes to high EMT/metastatic potential of cisplatin-resistant non-small cell lung cancer[J]. Oncotarget, 2016, 7(34): 55543-55554.
43	SINGH S, KARTHIKEYAN C, MOORTHY N S H N. Recent advances in the development of fatty acid synthase inhibitors as anticancer agents[J]. Mini Rev Med Chem, 2020, 20(18): 1820-1837.
44	WANG S, WANG N, ZHENG Y, et al. Caveolin-1: an oxidative stress-related target for cancer prevention[J]. Oxid Med Cell Longev, 2017, 2017: 7454031.
45	HESS D, CHISHOLM J W, IGAL R A. Inhibition of stearoylCoA desaturase activity blocks cell cycle progression and induces programmed cell death in lung cancer cells[J]. PLoS One, 2010, 5(6): e11394.
46	PISANU M E, NOTO A, DE VITIS C, et al. Blockade of Stearoyl-CoA-desaturase 1 activity reverts resistance to cisplatin in lung cancer stem cells[J]. Cancer Lett, 2017, 406: 93-104.
47	ZHANG J, SONG F, ZHAO X, et al. EGFR modulates monounsaturated fatty acid synthesis through phosphorylation of SCD1 in lung cancer[J]. Mol Cancer, 2017, 16(1): 127.
48	LONG J, ZHANG C J, ZHU N, et al. Lipid metabolism and carcinogenesis, cancer development[J]. Am J Cancer Res, 2018, 8(5): 778-791.
49	DAI C S, LEI L, LI B, et al. Involvement of the activation of Nrf2/HO-1, p38 MAPK signaling pathways and endoplasmic reticulum stress in furazolidone induced cytotoxicity and S phase arrest in human hepatocyte L02 cells: modulation of curcumin[J]. Toxicol Mech Methods, 2017, 27(3): 165-172.
50	GRUENBACHER G, THURNHER M. Mevalonate metabolism in immuno-oncology[J]. Front Immunol, 2017, 8: 1714.
51	VALLIANOU N G, KOSTANTINOU A, KOUGIAS M, et al. Statins and cancer[J]. Anticancer Agents Med Chem, 2014, 14(5): 706-712.
52	NGUYEN P A, CHANG C C, GALVIN C J, et al. Statins use and its impact in EGFR-TKIs resistance to prolong the survival of lung cancer patients: a Cancer registry cohort study in Taiwan[J]. Cancer Sci, 2020, 111(8): 2965-2973.
53	LIU Y, CHEN L, GONG Z, et al. Lovastatin enhances adenovirus-mediated TRAIL induced apoptosis by depleting cholesterol of lipid rafts and affecting CAR and death receptor expression of prostate cancer cells[J]. Oncotarget, 2015, 6(5): 3055-3070.
54	EMILSSON L, GARCÍA-ALBÉNIZ X, LOGAN R W, et al. Examining bias in studies of statin treatment and survival in patients with cancer[J]. JAMA Oncol, 2018, 4(1): 63-70.

[1]	黄治物, 吴皓. 年龄相关性听力损失研究进展与临床干预策略[J]. 上海交通大学学报（医学版）, 2022, 42(9): 1182-1187.
[2]	邹菁华, 宫淼淼, 沈瑛. KRAS4A^G12C和KRAS4B^G12C对人肺上皮细胞生长和运动的作用差异及机制研究[J]. 上海交通大学学报（医学版）, 2022, 42(8): 1016-1023.
[3]	赵珂珂, 蒋蓓蓓, 张璐, 王凌云, 张亚平, 解学乾. 超低剂量平扫CT深度学习图像重建评价肺部病灶的可行性[J]. 上海交通大学学报（医学版）, 2022, 42(8): 1062-1069.
[4]	沙攀, 赵雪雯, 朱浩天, 高崇洲, 刘珅. 肌腱粘连的机制及干预研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(8): 1116-1121.
[5]	廖雅慧, 刘丽云, 朱泓睿, 林厚文, 严继舟, 孙凡. 海绵来源的smenospongine通过抑制非小细胞肺癌细胞中的EGFR-Akt-ABCG2信号通路抑制顺铂耐药[J]. 上海交通大学学报（医学版）, 2022, 42(8): 997-1007.
[6]	张琳程, 钟华. 结节病的发病机制与临床治疗研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(7): 931-938.
[7]	王杨, 程佳月, 王振. 经颅直流电刺激作用机制的研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(7): 952-957.
[8]	张修齐, 沈柏用. 胰腺导管腺癌神经侵袭的细胞学机制研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(6): 833-838.
[9]	刘子杨, 王小文, 陈力. lncRNA GK-IT1通过调控醛缩酶A影响非小细胞肺癌细胞的恶性进展[J]. 上海交通大学学报（医学版）, 2022, 42(5): 591-601.
[10]	陆文清, 孟周文理, 虞永峰, 陆舜. 非小细胞肺癌第三代表皮生长因子受体-酪氨酸激酶抑制剂的耐药机制及治疗策略[J]. 上海交通大学学报（医学版）, 2022, 42(4): 535-544.
[11]	林艳艳, 许岩, 李慧. 儿童急性淋巴细胞白血病化学治疗常规药物耐药机制的研究进展[J]. 上海交通大学学报(医学版), 2022, 42(2): 211-217.
[12]	谢玉婷, 熊屏. 单原子催化剂的生物医学应用研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(12): 1751-1756.
[13]	廖洪建, 曹宇超, 杜永洪. 载药DNA纳米花对小鼠肺癌细胞的抑癌作用研究[J]. 上海交通大学学报（医学版）, 2022, 42(11): 1542-1549.
[14]	李若楠, 陈小科, 许元元, 谭强. ⅠB~ⅢA期非小细胞肺癌患者术后辅助靶向治疗研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(11): 1612-1619.
[15]	朱楠, 刘炳亚, 俞焙秦. 肌盲样蛋白1在恶性肿瘤中作用的研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(10): 1474-1481.

脂质代谢在肺癌发生发展及诊疗领域中的研究进展

Lipid metabolism and lung cancer: emerging roles in occurrence, progression, diagnosis and treatment

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 54

相关文章 15

编辑推荐

Metrics