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

doi:10.3969/j.issn.1674-8115.2022.12.016

Abstract

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

CLC Number:

R734.2

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.

TrendMD

References 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]	ZHAO Keke, JIANG Beibei, ZHANG Lu, WANG Lingyun, ZHANG Yaping, XIE Xueqian. Feasibility of ultra-low-dose noncontrast CT based on deep learning image reconstruction to evaluate chest lesions [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1062-1069.
[2]	SHA Pan, ZHAO Xuewen, ZHU Haotian, GAO Chongzhou, LIU Shen. Research progress in the mechanism and intervention of tendon adhesion [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1116-1121.
[3]	LIAO Yahui, LIU Liyun, ZHU Hongrui, LIN Houwen, YAN Jizhou, SUN Fan. Marine sponge-derived smenospongine overcomes resistance of cisplatin via inhibiting EGFR-Akt-ABCG2 pathway in NSCLC cells [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 997-1007.
[4]	WANG Yang, CHENG Jiayue, WANG Zhen. Progress in mechanism of transcranial direct current stimulation [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(7): 952-957.
[5]	ZHANG Xiuqi, SHEN Baiyong. Advances in cytological mechanism of neural invasion in pancreatic ductal adenocarcinoma [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(6): 833-838.
[6]	LIU Ziyang, WANG Xiaowen, CHEN Li. lncRNA GK-IT1 influences the carcinogenesis of non-small cell lung cancer cells through regulating aldolase A [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(5): 591-601.
[7]	LU Wenqing, MENG Zhouwenli, YU Yongfeng, LU Shun. Resistance mechanisms and overcoming strategies of the third-generation EGFR-TKI in non-small cell lung cancer [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(4): 535-544.
[8]	Yanyan LIN, Yan XU, Hui LI. Progress in research on the mechanism of drug resistance to conventional chemotherapeutic drugs in children with acute lymphoblastic leukemia [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2022, 42(2): 211-217.
[9]	XIE Yuting, XIONG Ping. Research advances in biomedical applications of single-atom catalysts [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(12): 1751-1756.
[10]	LIAO Hongjian, CAO Yuchao, DU Yonghong. Anticancer effect of drug-loaded DNA nanoflowers on mouse lung cancer cells [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(11): 1542-1549.
[11]	LI Ruonan, CHEN Xiaoke, XU Yuanyuan, TAN Qiang. Advances in postoperative adjuvant targeted therapy for patients with stage ⅠB-ⅢA non-small cell lung cancer [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(11): 1612-1619.
[12]	ZHU Nan, LIU Bingya, YU Beiqin. Advances in the role of muscle blind-like protein 1 in malignant tumors [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(10): 1474-1481.
[13]	Yu ZHANG, Xiaoyuan WU, Lihua GUAN, Yiyuan LIU, Xingyue PENG, Haiyan XIE, Wei HU, Keke HAO, Ning XIA, Guojun LU, Zhibo HOU. Application of high-throughput drug sensitivity screening system in the treatment of non-small cell lung cancer with malignant pleural effusion [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2022, 42(1): 82-89.
[14]	Bing-qian ZHOU, Li HAN, Zhe-yi CHEN, Shi-yu CHEN, Ying-xia ZHENG. Expression of protein arginine methyltransferase 5 in lung cancer and its mechanism of promoting lung cancer [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(8): 1009-1016.
[15]	Lei XIONG, Qian YI, Ming-fang XU, Jian CHEN. Expression and prognosis analysis of MRPL12 in lung adenocarcinoma [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(8): 1033-1040.