Reprogrammed lipid metabolism in advanced resistant cancers: an upcoming therapeutic opportunity

Mario Cioce , Mariamena Arbitrio , Nicoletta Polerà , Emanuela Altomare , Antonia Rizzuto , Carmela De Marco , Vito Michele Fazio , Giuseppe Viglietto , Maria Lucibello

Cancer Drug Resistance ›› 2024, Vol. 7 : 45

PDF
Cancer Drug Resistance ›› 2024, Vol. 7 :45 DOI: 10.20517/cdr.2024.131
review-article

Reprogrammed lipid metabolism in advanced resistant cancers: an upcoming therapeutic opportunity

Author information +
History +
PDF

Abstract

Resistance of cancer to therapy is the main challenge to its therapeutic management and is still an unsolved problem. Rearranged lipid metabolism is a strategy adopted by cancer cells to counteract adversity during their evolution toward aggressiveness and immune evasion. This relies on several mechanisms, ranging from altered metabolic pathways within cancer cells to evolved dynamic crosstalk between cancer cells and the tumor microenvironment (TME), with some cell populations at the forefront of metabolic reprogramming, thereby contributing to the resistance of the whole ecosystem during therapy. Unraveling these mechanisms may contribute to the development of more effective combinatorial therapy in resistant patients. This review highlights the alterations in lipid metabolism that contribute to cancer progression, with a focus on the potential clinical relevance of such findings for the management of therapy resistance.

Keywords

Metabolic signaling / therapy resistance / tumor microenvironment / metastasis / immune evasion

Cite this article

Download citation ▾
Mario Cioce, Mariamena Arbitrio, Nicoletta Polerà, Emanuela Altomare, Antonia Rizzuto, Carmela De Marco, Vito Michele Fazio, Giuseppe Viglietto, Maria Lucibello. Reprogrammed lipid metabolism in advanced resistant cancers: an upcoming therapeutic opportunity. Cancer Drug Resistance, 2024, 7: 45 DOI:10.20517/cdr.2024.131

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Marusyk A,Polyak K.Intratumor heterogeneity: the rosetta stone of therapy resistance.Cancer Cell2020;37:471-84 PMCID:PMC7181408

[2]

de Visser KE, Joyce JA. The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth.Cancer Cell2023;41:374-403

[3]

Zaytseva YY,Le AT.Preclinical evaluation of novel fatty acid synthase inhibitors in primary colorectal cancer cells and a patient-derived xenograft model of colorectal cancer.Oncotarget2018;9:24787-800 PMCID:PMC5973868

[4]

Jiang L,Sugiura H.Metabolic reprogramming during TGFβ1-induced epithelial-to-mesenchymal transition.Oncogene2015;34:3908-16 PMCID:PMC4387121

[5]

Kumar N.Cholesterol-lowering drugs on Akt signaling for prevention of tumorigenesis.Front Genet2021;12:724149 PMCID:PMC8483559

[6]

Shibue T.EMT, CSCs, and drug resistance: the mechanistic link and clinical implications.Nat Rev Clin Oncol2017;14:611-29 PMCID:PMC5720366

[7]

Levental I,Heberle FA.Lipid rafts: controversies resolved, mysteries remain.Trends Cell Biol2020;30:341-53 PMCID:PMC7798360

[8]

Greenlee JD,Liu K.Rafting down the metastatic cascade: the role of lipid rafts in cancer metastasis, cell death, and clinical outcomes.Cancer Res2021;81:5-17 PMCID:PMC7952000

[9]

Sanchez-Vega F, Mina M, Armenia J, et al; Cancer Genome Atlas Research Network. Oncogenic signaling pathways in the cancer genome atlas. Cell 2018;173:321-37.e10. PMCID:PMC6070353

[10]

Yu S,Che D.Targeting CRABP-II overcomes pancreatic cancer drug resistance by reversing lipid raft cholesterol accumulation and AKT survival signaling.J Exp Clin Cancer Res2022;41:88 PMCID:PMC8903155

[11]

Tamburrino D,Partelli S.Statin use improves survival in patients with pancreatic ductal adenocarcinoma: a meta-analysis.Dig Liver Dis2020;52:392-9

[12]

Zhao X,Sun W,Cui L.Targeting squalene epoxidase confers metabolic vulnerability and overcomes chemoresistance in HNSCC.Adv Sci2023;10:e2206878 PMCID:PMC10520660

[13]

Bi J,Zanca C.Oncogene amplification in growth factor signaling pathways renders cancers dependent on membrane lipid remodeling.Cell Metab2019;30:525-38.e8 PMCID:PMC6742496

[14]

Ding J,Leng Z.LPCAT1 promotes gefitinib resistance via upregulation of the EGFR/PI3K/AKT signaling pathway in lung adenocarcinoma.J Cancer2022;13:1837-47 PMCID:PMC8990424

[15]

Zhang H.LPCAT1 is transcriptionally regulated by FOXA1 to promote breast cancer progression and paclitaxel resistance.Oncol Lett2023;25:134 PMCID:PMC9996177

[16]

Sabtu SN,Looi LM.Indication of high lipid content in epithelial-mesenchymal transitions of breast tissues.Sci Rep2021;11:3250 PMCID:PMC7864999

[17]

De Las Rivas J, Brozovic A, Izraely S, Casas-Pais A, Witz IP, Figueroa A. Cancer drug resistance induced by EMT: novel therapeutic strategies.Arch Toxicol2021;95:2279-97 PMCID:PMC8241801

[18]

Xu Z,Dai H.Epithelial-mesenchymal transition-mediated tumor therapeutic resistance.Molecules2022;27:4750 PMCID:PMC9331826

[19]

Abdulla N,Kaur M.Mechanistic insights delineating the role of cholesterol in epithelial mesenchymal transition and drug resistance in cancer.Front Cell Dev Biol2021;9:728325 PMCID:PMC8640133

[20]

Deblois G,Tam IS.ERRα mediates metabolic adaptations driving lapatinib resistance in breast cancer.Nat Commun2016;7:12156 PMCID:PMC4945959

[21]

Mao X,Yi T.Lipid reprogramming induced by the TFEB-ERRα axis enhanced membrane fluidity to promote EC progression.J Exp Clin Cancer Res2022;41:28 PMCID:PMC8767755

[22]

Zhang C,Xia M.TFEB mediates immune evasion and resistance to mTOR inhibition of renal cell carcinoma via induction of PD-L1.Clin Cancer Res2019;25:6827-38

[23]

Zhang J,Ma J.ST3GAL5-catalyzed gangliosides inhibit TGF-β-induced epithelial-mesenchymal transition via TβRI degradation.EMBO J2023;42:e110553 PMCID:PMC9841337

[24]

Liu J,Wu J.Identification of ST3GAL5 as a prognostic biomarker correlating with CD8+ T cell exhaustion in clear cell renal cell carcinoma.Front Immunol2022;13:979605 PMCID:PMC9510991

[25]

Piacentino ML,Andrews CJ.Temporal changes in plasma membrane lipid content induce endocytosis to regulate developmental epithelial-to-mesenchymal transition.Proc Natl Acad Sci U S A2022;119:e2212879119 PMCID:PMC9907157

[26]

Muta Y,Martinez-Ordoñez A.Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis.Nat Commun2023;14:8075 PMCID:PMC10719313

[27]

Chen M,Sampieri K.An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer.Nat Genet2018;50:206-18 PMCID:PMC6714980

[28]

Choo M,Kim HS.Involvement of cell shape and lipid metabolism in glioblastoma resistance to temozolomide.Acta Pharmacol Sin2023;44:670-9 PMCID:PMC9958008

[29]

Longden J,Engel M.Deep neural networks identify signaling mechanisms of ErbB-family drug resistance from a continuous cell morphology space.Cell Rep2021;34:108657

[30]

Broadfield LA,Talebi A,Fendt SM.Lipid metabolism in cancer: new perspectives and emerging mechanisms.Dev Cell2021;56:1363-93

[31]

Bacci M,Smiriglia A.Acetyl-CoA carboxylase 1 controls a lipid droplet-peroxisome axis and is a vulnerability of endocrine-resistant ER+ breast cancer.Sci Transl Med2024;16:eadf9874

[32]

Monaco ME.Fatty acid metabolism in breast cancer subtypes.Oncotarget2017;8:29487-500 PMCID:PMC5438746

[33]

Luo J,Lu Y.Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive inhibition of the Warburg effect by cetuximab.Cancer Lett2017;384:39-49 PMCID:PMC5110372

[34]

Yun WJ,Yin NC.The promoting effects of GPR176 expression on proliferation, chemoresistance, lipogenesis and invasion of oesophageal cancer.J Cancer Res Clin Oncol2023;149:14641-55 PMCID:PMC10602955

[35]

Hunt EG,Riesenberg BP.Acetyl-CoA carboxylase obstructs CD8+ T cell lipid utilization in the tumor microenvironment.Cell Metab2024;36:969-83.e10

[36]

Vishwa R,Girisa S.Lipid metabolism and its implications in tumor cell plasticity and drug resistance: what we learned thus far?.Cancer Metastasis Rev2024;43:293-319

[37]

Kuo CY.When fats commit crimes: fatty acid metabolism, cancer stemness and therapeutic resistance.Cancer Commun2018;38:47 PMCID:PMC6042406

[38]

Bartolacci C,Vale G.Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer.Nat Commun2022;13:4327 PMCID:PMC9325712

[39]

Yang WS.Ferroptosis: death by lipid peroxidation.Trends Cell Biol2016;26:165-76 PMCID:PMC4764384

[40]

Bauerschlag DO,Leonhardt P.Fatty acid synthase overexpression: target for therapy and reversal of chemoresistance in ovarian cancer.J Transl Med2015;13:146 PMCID:PMC4504229

[41]

Al-Bahlani S,Al-Adawi M,Al-Dhahli B.Fatty acid synthase regulates the chemosensitivity of breast cancer cells to cisplatin-induced apoptosis.Apoptosis2017;22:865-76

[42]

Han L,Luo W.Enhanced de novo lipid synthesis mediated by FASN induces chemoresistance in colorectal cancer.Cancers2023;15:562 PMCID:PMC9913810

[43]

Castagnoli L,Franceschini A.Fatty acid synthase as a new therapeutic target for HER2-positive gastric cancer.Cell Oncol2023;46:661-76 PMCID:PMC10205874

[44]

Xiao Y,Xiong H.The implications of FASN in immune cell biology and related diseases.Cell Death Dis2024;15:88 PMCID:PMC10810964

[45]

Huang J,Fang XN.FASN inhibition decreases MHC-I degradation and synergizes with PD-L1 checkpoint blockade in hepatocellular carcinoma.Cancer Res2024;84:855-71

[46]

Lim SA,Nguyen TLM.Lipid signalling enforces functional specialization of Treg cells in tumours.Nature2021;591:306-11 PMCID:PMC8168716

[47]

Falchook G,Arkenau HT.First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors.EClinicalMedicine2021;34:100797 PMCID:PMC8040281

[48]

Qu Q,Liu X,Deng F.Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer.Cell Death Dis2016;7:e2226 PMCID:PMC4917665

[49]

Corbet C,Martherus R,Polet F.Acidosis drives the reprogramming of fatty acid metabolism in cancer cells through changes in mitochondrial and histone acetylation.Cell Metab2016;24:311-23

[50]

Munir R,Swinnen JV.Lipid metabolism in cancer cells under metabolic stress.Br J Cancer2019;120:1090-8 PMCID:PMC6738079

[51]

Pascual G,Mejetta S.Targeting metastasis-initiating cells through the fatty acid receptor CD36.Nature2017;541:41-5

[52]

Nath A.Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers.Sci Rep2016;6:18669 PMCID:PMC4698658

[53]

Tousignant KD,Taherian Fard A.Lipid uptake is an androgen-enhanced lipid supply pathway associated with prostate cancer disease progression and bone metastasis.Mol Cancer Res2019;17:1166-79

[54]

Ladanyi A,Kenny HA.Adipocyte-induced CD36 expression drives ovarian cancer progression and metastasis.Oncogene2018;37:2285-301 PMCID:PMC5920730

[55]

Aoki T,Munesue S.Hypoxia-induced CD36 expression in gastric cancer cells promotes peritoneal metastasis via fatty acid uptake.Ann Surg Oncol2023;30:3125-36 PMCID:PMC10085939

[56]

Tan Y,Zhao G.Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells.Nat Commun2022;13:4554 PMCID:PMC9356138

[57]

Feng WW,Bang S.CD36-mediated metabolic rewiring of breast cancer cells promotes resistance to HER2-targeted therapies.Cell Rep2019;29:3405-20.e5 PMCID:PMC6938262

[58]

Kubo M,Eguchi H.Impact of CD36 on chemoresistance in pancreatic ductal adenocarcinoma.Ann Surg Oncol2020;27:610-9

[59]

Zhang Y,Zhang Z,Zhu J.IL-6 promotes chemoresistance via upregulating CD36 mediated fatty acids uptake in acute myeloid leukemia.Exp Cell Res2022;415:113112

[60]

Mahalingam D,Patnaik A.First-in-human phase I dose escalation trial of the first-in-class tumor microenvironment modulator VT1021 in advanced solid tumors.Commun Med2024;4:10 PMCID:PMC10787778

[61]

Ma X,Liu L.CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability.Cell Metab2021;33:1001-12.e5 PMCID:PMC8102368

[62]

Han C,Xing P.Cystine deprivation triggers CD36-mediated ferroptosis and dysfunction of tumor infiltrating CD8+ T cells.Cell Death Dis2024;15:145 PMCID:PMC10869360

[63]

Wang H,Tsui YC.CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors.Nat Immunol2020;21:298-308 PMCID:PMC7043937

[64]

Darragh LB,Hu J.A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC.Nat Cancer2022;3:1300-17 PMCID:PMC9701140

[65]

Ross RB,Yu J.PPARα agonism enhances immune response to radiotherapy while dietary oleic acid results in counteraction.Clin Cancer Res2024;30:1916-33 PMCID:PMC11061609

[66]

Sun M,Häggström C.Metabolically (un)healthy obesity and risk of obesity-related cancers: a pooled study.J Natl Cancer Inst2023;115:456-67 PMCID:PMC10086630

[67]

Dyck L,Raverdeau M.Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function.J Exp Med2022;219:e20210042 PMCID:PMC8932531

[68]

Litton JK,Warneke CL.Relationship between obesity and pathologic response to neoadjuvant chemotherapy among women with operable breast cancer.J Clin Oncol2008;26:4072-7 PMCID:PMC6557586

[69]

Sparano JA,Zhao F.Obesity at diagnosis is associated with inferior outcomes in hormone receptor-positive operable breast cancer.Cancer2012;118:5937-46 PMCID:PMC3586227

[70]

Li YJ,Aftabizadeh M.Fatty acid oxidation protects cancer cells from apoptosis by increasing mitochondrial membrane lipids.Cell Rep2022;39:110870

[71]

Mukherjee A,Daifotis HA.Adipocyte-induced FABP4 expression in ovarian cancer cells promotes metastasis and mediates carboplatin resistance.Cancer Res2020;80:1748-61 PMCID:PMC10656748

[72]

Nguyen HL,Maetens M.Obesity-associated changes in molecular biology of primary breast cancer.Nat Commun2023;14:4418 PMCID:PMC10361985

[73]

Azrad M,Demark-Wahnefried W.Current evidence linking polyunsaturated fatty acids with cancer risk and progression.Front Oncol2013;3:224 PMCID:PMC3761560

[74]

Roodhart JML,Stigter ECA.Mesenchymal stem cells induce resistance to chemotherapy through the release of platinum-induced fatty acids.Cancer Cell2011;20:370-83

[75]

Cioce M,Pass H,Strano S.Arachidonic acid drives adaptive responses to chemotherapy-induced stress in malignant mesothelioma.J Exp Clin Cancer Res2021;40:344 PMCID:PMC8561918

[76]

Yang Y.Editorial: The adipose tissue microenvironment in cancer: molecular mechanisms and targets for treatment.Front Cell Dev Biol2022;10:954645 PMCID:PMC9627479

[77]

Dong QT,Gong Q.FAM3 family genes are associated with prognostic value of human cancer: a pan-cancer analysis.Sci Rep2023;13:15144 PMCID:PMC10499837

[78]

Dirat B,Dabek M.Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion.Cancer Res2011;71:2455-65

[79]

Huang R,Hong J.Targeting cancer-associated adipocyte-derived CXCL8 inhibits triple-negative breast cancer progression and enhances the efficacy of anti-PD-1 immunotherapy.Cell Death Dis2023;14:703 PMCID:PMC10613226

[80]

Liu H,Tan L.Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma.Cancer Cell2023;41:693-710.e8

[81]

Schalper KA,Zhou M.Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors.Nat Med2020;26:688-92 PMCID:PMC8127102

[82]

Zhai J,Xie G.Cancer-associated fibroblasts-derived IL-8 mediates resistance to cisplatin in human gastric cancer.Cancer Lett2019;454:37-43

[83]

Hosni S,Klümper N.Adipocyte precursor-derived NRG1 promotes resistance to FGFR inhibition in urothelial carcinoma.Cancer Res2024;84:725-40 PMCID:PMC10911805

[84]

Wang YY,Wu YC.ADSCs stimulated by resistin promote breast cancer cell malignancy via CXCL5 in a breast cancer coculture model.Sci Rep2022;12:15437 PMCID:PMC9475041

[85]

Giuliano S,Ndiaye PD.Resistance to lysosomotropic drugs used to treat kidney and breast cancers involves autophagy and inflammation and converges in inducing CXCL5.Theranostics2019;9:1181-99 PMCID:PMC6401402

[86]

Deng T,Tong Y.Crosstalk between endothelial progenitor cells and HCC through periostin/CCL2/CD36 supports formation of the pro-metastatic microenvironment in HCC.Oncogene2024;43:944-61

[87]

Nakazawa Y,Sanada F.Periostin blockade overcomes chemoresistance via restricting the expansion of mesenchymal tumor subpopulations in breast cancer.Sci Rep2018;8:4013 PMCID:PMC5838092

[88]

Ringel AE,Baker GJ.Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity.Cell2020;183:1848-66.e26 PMCID:PMC8064125

[89]

Tang LR,Cai SL.Prolyl hydroxylase domain 3 influences the radiotherapy efficacy of pancreatic cancer cells by targeting hypoxia-inducible factor-1α.Onco Targets Ther2018;11:8507-15 PMCID:PMC6278705

[90]

Dopeso H,Cuesta AM.PHD3 controls lung cancer metastasis and resistance to EGFR inhibitors through TGFα.Cancer Res2018;78:1805-19

[91]

Piening A,Gottlieb C.Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk.Nat Commun2024;15:2835 PMCID:PMC10987624

AI Summary AI Mindmap
PDF

146

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/