脂滴表面蛋白perilipin家族在癌症中的研究进展

王群; 孙雨欣; 王海峰

doi:10.12259/j.issn.2095-610X.S20230812

脂滴表面蛋白perilipin家族在癌症中的研究进展

doi: 10.12259/j.issn.2095-610X.S20230812

昆明医科大学第二附属医院泌尿外科，云南昆明　650106

基金项目: 国家自然科学基金资助项目（82060464）；云南省科技厅-昆明医科大学联合应用基础研究重点项目（202001AY070001-163）

详细信息

作者简介:
王群（1997～），女，湖南怀化人，在读硕士研究生，主要从事泌尿系统肿瘤的临床与基础研究工作

通讯作者:
王海峰，E-mail：wanghaifeng@kmmu.edu.cn

中图分类号: R34;R73
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出版历程
- 收稿日期: 2023-06-07
- 网络出版日期: 2023-09-02
- 刊出日期: 2023-08-30

Research Progress of Perilipin Family of Lipid Droplet Surface Proteins in Cancer

Dept. of Urology，The Second Affiliated Hospital of Kunming Medical University， Kunming Yunnan 650106，China

摘要

摘要: 随着癌症逐渐的年轻化，以及日益增加的发生率与死亡率，人们越来越关注其的发生发展。不可忽视的是目前全球肥胖人口也处于上升趋势，越来越多的研究发现肥胖会导致患癌症的风险增加，脂质代谢异常更是癌症中突出的代谢改变之一。故而，关注脂质代谢在癌症中所扮演的角色显得格外重要。近些年，随着人们深入学习了解脂质代谢，发现了脂滴表面蛋白Perilipin家族，其功能不仅仅是脂滴的结构蛋白，其与癌细胞的增殖、侵袭及转移等都密切相关。因此，Perilipin家族可能成为癌症治疗的一个潜在的有希望的靶点。主要综述了Perilipin家族各成员最新发现的在癌症中的作用及相关机制，这些研究将加深对Perilipin家族在癌症进展过程中的功能的认识，为更好预防控制癌症提供新的切入点。
- 癌症 /
- 脂滴 /
- 脂滴表面蛋白Perilipin家族 /
- 脂质代谢
Abstract: With cancer becoming increasingly prevalent and affecting younger populations, there is growing concern about its development and progression. It is worth noting that the global population of obese individuals is also on the rise, and numerous studies have found that obesity increases the risk of developing cancer. Abnormal lipid metabolism is one of the prominent metabolic changes in cancer development. Therefore, it is crucial to pay attention to the role of lipid metabolism in cancer. In recent years, as researchers have delved deeper into the study of lipid metabolism, the perilipin family of lipid droplet surface proteins has been discovered. These proteins not only serve as structural proteins for lipid droplets, but they are also closely associated with cancer cell proliferation, invasion, and metastasis. Therefore, the perilipin family may represent a potential and promising target for cancer treatment. This review primarily focuses on the latest findings regarding the roles and mechanisms of the perilipin family members in cancer. These studies will deepen our understanding of the functions of the perilipin family in the progression of cancer and provide new insights for better cancer prevention and control.
- Cancer /
- Lipid droplets /
- Perilipin family of lipid droplet surface proteins /
- Lipid metabolism

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表 1 PLINs在不同癌症中的作用及其机制

Table 1. The role and mechanism of PLINs in different cancers

PLINs	癌症类型	作用	潜在机制及通路	参考文献
PLIN1	乳腺癌	抑癌	ARAP1-AS1经miR-2110/HDAC2/PLIN1轴加速乳腺癌细胞增殖和迁移	[14]
	脂肪肉瘤	促癌	--	[17]
PLIN2	肾透明细胞癌	抑癌	--	[18]
	肝细胞癌	促癌	PLIN2通过抑制HCC细胞中AMPK/ULK1/自噬途径的活性调节HIF-1α，从而促进肝细胞癌细胞增殖	[21]
	恶性黑色素瘤	促癌	--	[34]
	肺腺癌	促癌	--	[35]
	子宫平滑肌瘤	促癌	PLIN2耗竭导致平滑肌瘤细胞内的线粒呼吸和糖酵解增加，从而诱导平滑肌瘤细胞增殖	[36]
PLIN3	肾透明细胞癌	促癌	--	[24]
	前列腺癌	促癌	ACSS3将AIP4 E3泛素连接酶募集到滴上，以调节PLIN3的泛素化水，抑制前列腺癌的进展	[25]
	脂肪肉瘤	促癌	--	[16]
	肝细胞癌	促癌	--	[26]
PLIN4	乳腺癌	促癌	--	[28]
PLIN5	肝细胞癌	促癌	--	[32]
	胃癌	促癌	--	[37]
	胰腺癌	促癌	--	[38]
注：ARAP1-AS1为长链非编码RNA（lncRNA）；HDAC2为组蛋白脱乙酰基酶2；HCC为肝细胞癌；AMPK为AMP激活蛋白激酶；ULK1为自噬启动蛋白1；HIF-1α为低氧诱导因子-1（HIF-1）的调节亚基。

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参考文献(41)

[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. doi: 10.3322/caac.21660
[2]	Balaban S,Shearer R F,Lee LS,et al. Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration[J]. Cancer Metab,2017,5:1. doi: 10.1186/s40170-016-0163-7
[3]	Pascual G,Avgustinova A,Mejetta S,et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36[J]. Nature,2017,541(7635):41-45. doi: 10.1038/nature20791
[4]	Roberts M A,Olzmann J A. Protein quality control and lipid droplet metabolism[J]. Annu Rev Cell Dev Biol,2020,36:115-139. doi: 10.1146/annurev-cellbio-031320-101827
[5]	Zadoorian A,Du X,Yang H. Lipid droplet biogenesis and functions in health and disease[J]. Nat Rev Endocrinol,2023,19(8):443-459. doi: 10.1038/s41574-023-00845-0
[6]	Bersuker K,Peterson C W H,To M,et al. A Proximity Labeling Strategy Provides Insights into the Composition and Dynamics of Lipid Droplet Proteomes[J]. Dev Cell,2018,44(1):97-112. doi: 10.1016/j.devcel.2017.11.020
[7]	Olzmann J A,Carvalho P. Dynamics and functions of lipid droplets[J]. Nat Rev Mol Cell Biol,2019,20(3):137-155. doi: 10.1038/s41580-018-0085-z
[8]	Li Z,Liu H,Luo X. Lipid droplet and its implication in cancer progression[J]. Am J Cancer Res,2020,10(12):4112-4122.
[9]	Schulze R J,McNiven M A. Lipid Droplet Formation and Lipophagy in Fatty Liver Disease[J]. Semin Liver Dis,2019,39(3):283-290. doi: 10.1055/s-0039-1685524
[10]	Luo W,Wang H,Ren L,et al. Adding fuel to the fire: The lipid droplet and its associated proteins in cancer progression[J]. Int J Biol Sci,2022,18(16):6020-6034. doi: 10.7150/ijbs.74902
[11]	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. doi: 10.1038/s41419-020-2297-3
[12]	Zhang Q,Zhang P,Li B,et al. The Expression of Perilipin Family Proteins can be used as Diagnostic Markers of Liposarcoma and to Differentiate Subtypes[J]. J Cancer,2020,11(14):4081-4090. doi: 10.7150/jca.41736
[13]	Zhang X,Su L,Sun K. Expression status and prognostic value of the perilipin family of genes in breast cancer[J]. Am J Transl Res,2021,13(5):4450-4463.
[14]	Lu C,Wang X,Zhao X,et al. Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis[J]. Biosci Rep,2020,40(4):20191764.
[15]	Zhai G,Pang Y,Zou Y,et al. Effects of PLIN1 Gene Knockout on the Proliferation,Apoptosis,Differentiation and Lipolysis of Chicken Preadipocytes[J]. Animals (Basel),2022,13(1):92. doi: 10.3390/ani13010092
[16]	Straub B K,Witzel H R,Pawella L M,et al. Perilipin 1 Expression Differentiates Liposarcoma from Other Types of Soft Tissue Sarcoma[J]. Am J Pathol,2019,189(8):1547-1558. doi: 10.1016/j.ajpath.2019.04.017
[17]	Meng L X,Zheng Y X,He M L,et al. Silencing of perilipin by short hairpin RNA inhibits proliferation and induces apoptosis in liposarcoma cells[J]. Mol Med Rep,2018,18(5):4571-4576.
[18]	Cao Q,Ruan H,Wang K,et al. Overexpression of PLIN2 is a prognostic marker and attenuates tumor progression in clear cell renal cell carcinoma[J]. Int J Oncol,2018,53(1):137-147.
[19]	Hashimoto Y,Ishida M,Ryota H,et al. Adipophilin expression is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma: An immunohistochemical analysis[J]. Pancreatology,2019,19(3):443-448. doi: 10.1016/j.pan.2019.03.001
[20]	Hu R,Gupta R,Wang Z,et al. Bioplasmonic paper-based assay for perilipin-2 non-invasively detects renal cancer[J]. Kidney Int,2019,96(6):1417-1421. doi: 10.1016/j.kint.2019.08.020
[21]	Liu W,Liu X,Liu Y,et al. PLIN2 promotes HCC cells proliferation by inhibiting the degradation of HIF1α[J]. Exp Cell Res,2022,418(1):113244. doi: 10.1016/j.yexcr.2022.113244
[22]	Roberts M A,Deol K K,Mathiowetz A J,et al. Parallel CRISPR-Cas9 screens identify mechanisms of PLIN2 and lipid droplet regulation[J]. Dev Cell,2023,5807(23):331-333.
[23]	Gu Y,Yang Y,Cao X,et al. Plin3 protects against alcoholic liver injury by facilitating lipid export from the endoplasmic reticulum[J]. J Cell Biochem,2019,120(9):16075-16087. doi: 10.1002/jcb.28889
[24]	Yao D,Xia S,Jin C,et al. Feedback activation of GATA1/miR-885-5p/PLIN3 pathway decreases sunitinib sensitivity in clear cell renal cell carcinoma[J]. Cell Cycle,2020,19(17):2195-2206. doi: 10.1080/15384101.2020.1801189
[25]	Zhou L,Song Z,Hu J,et al. ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3[J]. Theranostics,2021,11(2):841-860. doi: 10.7150/thno.49384
[26]	Zhang Y,Liang X,Lian Q,et al. Transcriptional analysis of the expression and prognostic value of lipid droplet-localized proteins in hepatocellular carcinoma[J]. BMC Cancer,2023,23(1):677. doi: 10.1186/s12885-023-10987-z
[27]	Zhu L,Hu F,Li C,et al. Perilipin 4 protein: an impending target for amyotrophic lateral sclerosis[J]. Mol Neurobiol,2021,58(4):1723-1737. doi: 10.1007/s12035-020-02217-5
[28]	Sirois I,Aguilar-Mahecha A,Lafleur J,et al. A unique morphological phenotype in chemoresistant triple-negative breast cancer reveals metabolic reprogramming and PLIN4 expression as a molecular vulnerability[J]. Mol Cancer Res,2019,17(12):2492-2507. doi: 10.1158/1541-7786.MCR-19-0264
[29]	Krizanac M,Mass Sanchez P B,et al. Lipid-Independent Regulation of PLIN5 via IL-6 through the JAK/STAT3 Axis in Hep3B Cells[J]. Int J Mol Sci,2023,24(8):7219. doi: 10.3390/ijms24087219
[30]	Zhang E,Cui W,Lopresti M,et al. Hepatic PLIN5 signals via SIRT1 to promote autophagy and prevent inflammation during fasting[J]. J Lipid Res,2020,61(3):338-350. doi: 10.1194/jlr.RA119000336
[31]	Di J,Chai Y,Yang X,et al. ELP6 and PLIN5 mutations were probably prognostic biomarkers for patients with gastric cancer[J]. Front Med (Lausanne),2022,9:803617. doi: 10.3389/fmed.2022.803617
[32]	Asimakopoulou A,Vucur M,Luedde T,et al. Perilipin 5 and lipocalin 2 expression in hepatocellular carcinoma[J]. Cancers (Basel),2019,11(3):385. doi: 10.3390/cancers11030385
[33]	Najt C P, Devarajan M, Mashek D G. Perilipins at a glance [J]. J Cell Sci, 2022, 135（5）: 110.
[34]	Fujimoto M,Matsuzaki I,Nishitsuji K,et al. Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis[J]. Lab Invest,2020,100(5):727-737. doi: 10.1038/s41374-019-0358-y
[35]	Alabiad M A,Harb O A,Abozaid M,et al. The diagnostic and prognostic roles of combined expression of novel biomarkers in lung adenocarcinoma and lung squamous cell carcinoma: An immunohistochemical study[J]. Iran J Pathol,2021,16(2):162-173. doi: 10.30699/ijp.2020.130944.2452
[36]	Okeigwe I,Bulun S,Liu S,et al. PLIN2 functions as a novel link between progesterone signaling and metabolism in uterine leiomyoma cells[J]. J Clin Endocrinol Metab,2019,104(12):6256-6264.
[37]	Burlaka A P,Ganusevich I I,Vovk A V,et al. Redox state of adipose tissue for patients with gastric cancer and its connection with the body mass index and distance from the tumor[J]. Obes Res Clin Pract,2020,14(1):34-38. doi: 10.1016/j.orcp.2019.10.003
[38]	Bai R,Rebelo A,Kleeff J,et al. Identification of prognostic lipid droplet-associated genes in pancreatic cancer patients via bioinformatics analysis[J]. Lipids Health Dis,2021,20(1):58. doi: 10.1186/s12944-021-01476-y
[39]	Martínez-Reyes I,Chandel N S. Cancer metabolism: looking forward[J]. Nat Rev Cancer,2021,21(10):669-680. doi: 10.1038/s41568-021-00378-6
[40]	Bian X, Liu R, Meng Y, et al. Lipid metabolism and cancer [J]. J Exp Med, 2021, 218（1）: 64.
[41]	Broadfield L A,Pane A A,Talebi A,et al. Lipid metabolism in cancer: New perspectives and emerging mechanisms[J]. Dev Cell,2021,56(10):1363-1393. doi: 10.1016/j.devcel.2021.04.013

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