脂质代谢在皮肤恶性肿瘤发生发展及诊疗中的研究进展

doi:10.35541/cjd.20240137

Abstract

Abstract: 【Abstract】 The incidence and mortality of skin malignant tumors have been increasing year by year, characterized by high invasiveness and poor prognosis, posing a serious threat to patients' lives. Lipid metabolism plays a critical role in tumor occurrence and development by providing essential material support for tumor cell activities. Dysregulation of lipid metabolism can interfere with inflammatory mediators, metabolites, and signaling pathways, leading to abnormal gene and protein expression, thereby promoting the malignant transformation, invasion, and metastasis of tumor cells. In recent years, research on lipid metabolism in skin malignant tumors has deepened, and therapies targeting lipid metabolism have gained increasing importance in their treatment. This review summarizes the molecular mechanisms of lipid metabolism in the occurrence and development of melanoma, squamous cell carcinoma, Kaposi sarcoma, and basal cell carcinoma, and outlines diagnostic and therapeutic strategies targeting lipid metabolism.

Key words: Skin malignant tumors, lipid metabolism, melanoma, squeous cell carcinoma, Kaposi sarcoma, basal cell carcinoma, pathogenesis, targeted treatment

Xue Shuyue, Li Tingting, Kang Xiaojing. Lipid metabolism in the occurrence, development, diagnosis and treatment of cutaneous malignancies[J]. Chinese Journal of Dermatology, 2026, 59(4): 379-382.doi:10.35541/cjd.20240137

References ［36］

［1］	Linares MA, Zakaria A, Nizran P. Skin cancer［J］. Primary Care, 2015, 42（4）: 645⁃659. DOI: 10.1016/j.pop.2015.07.006.
［2］	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.
［3］	Celis Ramírez AM, Amézquita A, Cardona Jaramillo J, et al. Analysis of malassezia lipidome disclosed differences among the species and reveals presence of unusual yeast lipids［J］. Front Cell Infect Microbiol, 2020,10:338. DOI: 10.3389/fcimb.2020. 00338.
［4］	Guo WN, Li CY. Linking cellular metabolism to epigenetics in melanoma［J］. Int J Dermatol Venerol, 2021, 4（3）: 168⁃173. DOI: 10.1097/JD9.0000000000000191.
［5］	Yan K, Zhang W, Song H, et al. Sphingolipid metabolism and regulated cell death in malignant melanoma［J］. Apoptosis, 2024,29（11⁃12）:1860⁃1878. DOI: 10.1007/s10495⁃024⁃02002⁃y.
［6］	Noujarède J, Carrié L, Garcia V, et al. Sphingolipid paracrine signaling impairs keratinocyte adhesion to promote melanoma invasion［J］. Cell Rep, 2023,42（12）:113586. DOI: 10.1016/j.celrep.2023.113586.
［7］	Kilkenny DM, Rocheleau JV. The FGF21 receptor signaling complex: klothoβ, FGFR1c, and other regulatory interactions［J］. Vitam Horm, 2016,101:17⁃58. DOI: 10.1016/bs.vh.2016.02.008.
［8］	陈诚, 张学军. 成纤维细胞生长因子21通过调控细胞脂代谢促进恶性黑色素瘤细胞生长［J］. 中华整形外科杂志, 2019,35（6）:593⁃600. DOI: 10.3760/cma.j.issn.1009⁃4598.2019.06.015.
［9］	Stamatakos S, Beretta GL, Vergani E, et al. Deregulated FASN expression in BRAF inhibitor⁃resistant melanoma cells unveils new targets for drug combinations［J］. Cancers （Basel）, 2021,13（9）:2284. DOI: 10.3390/cancers13092284.
［10］	Madhunapantula SV, Hengst J, Gowda R, et al. Targeting sphingosine kinase⁃1 to inhibit melanoma［J］. Pigment Cell & Melanoma Research, 2012,25（2）:259⁃274. DOI: 10.1111/j.1755⁃148X.2012.00970.x.
［11］	McCarty MF. GCN2 and FGF21 are likely mediators of the protection from cancer, autoimmunity, obesity, and diabetes afforded by vegan diets［J］. Med Hypotheses, 2014,83（3）:365⁃371. DOI: 10.1016/j.mehy.2014.06.014.
［12］	Caudill J, Thomas JE, Burkhart CG. The risk of metastases from squamous cell carcinoma of the skin［J］. Int J Dermatol, 2023,62（4）:483⁃486. DOI: 10.1111/ijd.16164.
［13］	Mei LH, Gan HH, Wang HF, et al. Lipidomics revealed alterations in glycerophospholipid metabolism in skin squamous cell carcinoma［J］. Front Mol Biosci, 2024,11:1356043. DOI: 10.3389/fmolb.2024.1356043.
［14］	Dickinson A, Saraswat M, Joenväärä S, et al. Mass spectrometry⁃based lipidomics of oral squamous cell carcinoma tissue reveals aberrant cholesterol and glycerophospholipid metabolism—a pilot study［J］. Translational Oncology, 2020,13（10）:100807. DOI: 10.1016/j.tranon.2020.100807.
［15］	Zeng W, Zheng W, Hu S, et al. Application of lipidomics for assessing tissue lipid profiles of patients with squamous cell carcinoma［J］. Technol Cancer Res Treat, 2021,20:1533033821 1049903. DOI: 10.1177/15330338211049903.
［16］	Reed D, Kumar D, Kumar S, et al. Transcriptome and metabolome changes induced by bitter melon （momordica charantia）⁃ intake in a high⁃fat diet induced obesity model［J］. J Tradit Complement Med, 2022,12（3）:287⁃301. DOI: 10.1016/j.jtcme.2021.08.011.
［17］	Huang Y, Wang Y, Wang Y, et al. LPCAT1 promotes cutaneous squamous cell carcinoma via EGFR⁃mediated protein kinase B/p38MAPK signaling pathways［J］. J Invest Dermatol, 2022,142（2）:303⁃313. DOI: 10.1016/j.jid.2021.07.163.
［18］	Ogretmen B. Sphingolipid metabolism in cancer signalling and therapy［J］. Nat Rev Cancer, 2018,18（1）:33⁃50. DOI: 10.1038/nrc.2017.96.
［19］	Gong ZH, Ji J, Yao J, et al. SphK1⁃targeted miR⁃6784 inhibits functions of skin squamous cell carcinoma cells［J］. Aging, 2021,13（3）:3726⁃3741. DOI: 10.18632/aging.202336.
［20］	Liu Z, Li P, Yang YQ, et al. I⁃BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo［J］. Cell Death Dis, 2020,11（5）:318. DOI: 10.1038/s41419⁃020⁃2515⁃z.
［21］	中国医师协会皮肤科医师分会, 中国研究型医院学会皮肤科学专业委员会. 中国卡波西肉瘤诊疗专家共识（2023版）［J］. 中华皮肤科杂志, 2023,56（10）:899⁃906. DOI: 10.35541/cjd. 20230261.
［22］	Chandrasekharan JA, Sharma⁃Walia N. Arachidonic acid derived lipid mediators influence Kaposi's sarcoma⁃associated herpesvirus infection and pathogenesis［J］. Front Microbiol, 2019,10:358. DOI: 10.3389/fmicb.2019.00358.
［23］	O'Callaghan G, Houston A. Prostaglandin E2 and the EP receptors in malignancy: possible therapeutic targets?［J］. Br J Pharmacol, 2015,172（22）:5239⁃5250. DOI: 10.1111/bph.13331.
［24］	Sharma⁃Walia N, Chandran K, Patel K, et al. The Kaposi's sarcoma⁃associated herpesvirus （KSHV）⁃induced 5⁃lipoxygenase⁃leukotriene B4 cascade plays key roles in KSHV latency, monocyte recruitment, and lipogenesis［J］. J Virol, 2014,88（4）:2131⁃2156. DOI: 10.1128/JVI.02786⁃13.
［25］	Teh N, Leow LJ. The role of actin in muscle spasms in a case series of patients with advanced basal cell carcinoma treated with a hedgehog pathway inhibitor［J］. Dermatol Ther （Heidelb）, 2021,11（1）:293⁃299. DOI: 10.1007/s13555⁃020⁃00464⁃x.
［26］	Pellegrini C, Maturo M, Di Nardo L, et al. Understanding the molecular genetics of basal cell carcinoma［J］. Int J Mol Sci, 2017, 18（11）: 2485. DOI: 10.3390/ijms18112485.
［27］	Ingham PW, Nakano Y, Seger C. Mechanisms and functions of Hedgehog signalling across the metazoa［J］. Nat Rev Genet, 2011,12（6）:393⁃406. DOI: 10.1038/nrg2984.
［28］	Raleigh DR, Sever N, Choksi PK, et al. Cilia⁃associated oxysterols activate smoothened［J］. Mol Cell, 2018,72（2）:316⁃327. DOI: 10.1016/j.molcel.2018.08.034.
［29］	Daggubati V, Vykunta A, Choudhury A, et al. Hedgehog target genes regulate lipid metabolism to drive basal cell carcinoma and medulloblastoma［J］. Res Sq, 2023:rs.3.rs⁃3058335 ［pii］. DOI: 10.21203/rs.3.rs⁃3058335/v1.
［30］	Ganjali S, Banach M, Pirro M, et al. HDL and cancer ⁃ causality still needs to be confirmed? Update 2020［J］. Semin Cancer Biol, 2021,73:169⁃177. DOI: 10.1016/j.semcancer.2020.10.007.
［31］	Huang B, Song BL, Xu C. Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities［J］. Nat Metab, 2020,2（2）:132⁃141. DOI: 10.1038/s42255⁃020⁃0174⁃0.
［32］	Raleigh DR, Algazi A, Arron ST, et al. Induction Hedgehog pathway inhibition followed by combined⁃modality radiotherapy for basal cell carcinoma［J］. Br J Dermatol, 2015,173（2）:544⁃546. DOI: 10.1111/bjd.13748.
［33］	国家皮肤与免疫疾病临床医学研究中心, 中国医师协会皮肤科分会. 中国皮肤基底细胞癌诊疗指南（2023版）［J］. 中华医学杂志, 2024,104（6）:391⁃410. DOI: 10.3760/cma.j.cn112137⁃20231113⁃01082.
［34］	Gordon RE, Zhang L, Peri S, et al. Statins synergize with Hedgehog pathway inhibitors for treatment of medulloblastoma［J］. Clinical Cancer Research, 2018,24（6）:1375⁃1388. DOI: 10.1158/1078⁃0432.CCR⁃17⁃2923.
［35］	Lucas JT Jr, Wright KD. Vismodegib and physeal closure in a pediatric patient［J］. Pediatr Blood Cancer, 2016,63（11）:2058. DOI: 10.1002/pbc.25941.
［36］	Raleigh DR, Choksi PK, Krup AL, et al. Hedgehog signaling drives medulloblastoma growth via CDK6［J］. J Clin Invest, 2018,128（1）:120⁃124. DOI: 10.1172/JCI92710.

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Lipid metabolism in the occurrence, development, diagnosis and treatment of cutaneous malignancies

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