FABP4在肿瘤中作用的研究进展

姬 艳琦, 徐 碧宇, 杨 晶玉, 常 粒园, 宋 旭东
华北理工大学附属医院病理科 河北唐山 063000

摘要

摘要：FABP4是一种低分子量、高度保守的胞浆蛋白，主要在脂肪细胞和巨噬细胞中表达，其水平的异常与多种心血管和代谢性疾病的发生发展有关。此外，FABP4与肿瘤的发生发展关系密切，其表达与乳腺癌、卵巢癌、胃癌、前列腺癌等肿瘤的增殖能力、侵袭性及生存预后显著相关。本文对FABP4的结构和生物学功能以及它在多种肿瘤中的表达情况及作用进行综述，旨在为肿瘤提供一种潜在的生物标志物和治疗新靶点。

关键词

关键词：FABP4；脂肪酸结合蛋白；肿瘤

参考

[1] Prentice K J, Saksi J, Hotamisligil G S. Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses[J]. J Lipid Res, 2019, 60(4): 734-740.[2] Zhou J, Deng Z, Chen Y, et al. Overexpression of FABP7 promotes cell growth and predicts poor prognosis of clear cell renal cell carcinoma[J]. Urol Oncol, 2015, 33(3): 113.e9-17.[3] Storch J, Mcdermott L. Structural and functional analysis of fatty acid-binding proteins[J]. J Lipid Res, 2009, 50 Suppl(Suppl): S126-31.[4] Hotamisligil G S, Bernlohr D A. Metabolic functions of FABPs--mechanisms and therapeutic implications[J]. Nat Rev Endocrinol, 2015, 11(10): 592-605.[5] Furuhashi M. Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases[J]. J Atheroscler Thromb, 2019, 26(3): 216-232.[6] Ota H, Furuhashi M, Ishimura S, et al. Elevation of fatty acid-binding protein 4 is predisposed by family history of hypertensionand contributes to blood pressure elevation[J]. Am J Hypertens, 2012, 25(10): 1124-30.[7] Furuhashi M, Ishimura S, Ota H, et al. Lipid chaperones and metabolic inflammation[J]. Int J Inflam, 2011, 2011: 642612.[8] Damon M, Louveau I, Lefaucheur L, et al. Number of intramuscular adipocytes and fatty acid binding protein-4 content are significant indicators of intramuscular fat level in crossbred Large White x Duroc pigs[J]. J Anim Sci, 2006, 84(5): 1083-92.[9] Neuhouser M L, Aragaki A K, Prentice R L, et al. Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials[J]. JAMA Oncol, 2015, 1(5): 611-21.[10] Zeng J, Sauter E R, Li B. FABP4: A New Player in Obesity-Associated Breast Cancer[J]. Trends Mol Med, 2020, 26(5): 437-440.[11] Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin J J, et al. Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention[J]. CA Cancer J Clin, 2017, 67(5): 378-397.[12] Hao J, Yan F, Zhang Y, et al. Expression of Adipocyte/Macrophage Fatty Acid-Binding Protein in Tumor-Associated Macrophages Promotes Breast Cancer Progression[J]. Cancer Res, 2018, 78(9): 2343-2355.[13] Gyamfi J, Yeo J H, Kwon D, et al. Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer[J]. NPJ Breast Cancer, 2021, 7(1): 129.[14] Guaita-Esteruelas S, Bosquet A, Saavedra P, et al. Exogenous FABP4 increases breast cancer cell proliferation and activates the expression of fatty acid transport proteins[J]. Mol Carcinog, 2017, 56(1): 208-217.[15] Gharpure K M, Pradeep S, Sans M, et al. FABP4 as a key determinant of metastatic potential of ovarian cancer[J]. Nat Commun, 2018, 9(1): 2923.[16] 莫佳娅, 苏引利, 段浩然, et al. 脂肪酸结合蛋白 4 在卵巢癌中的表达及其对卵巢癌细胞上皮间充质转化的影响[J]. 河南医学研究, 2022, 31(14): 2501-2506.[17] Guo Y, Wang Z W, Su W H, et al. Prognostic Value and Immune Infiltrates of ABCA8 and FABP4 in Stomach Adenocarcinoma[J]. Biomed Res Int, 2020, 2020: 4145164.[18] 陈起跃. 胃癌侵袭转移中 FABP4 起抑癌基因作用及其分子机制研究[D]. 福建医科大学, 2020.[19] Sun N, Zhao X. Therapeutic Implications of FABP4 in Cancer: An Emerging Target to Tackle Cancer[J]. Front Pharmacol, 2022, 13: 948610.[20] Liu L, Mo M, Chen X, et al. Targeting inhibition of prognosis-related lipid metabolism genes including CYP19A1 enhances immunotherapeutic response in colon cancer[J]. J Exp Clin Cancer Res, 2023, 42(1): 85.[21] Li C, Zhang L, Qiu Z, et al. Key Molecules of Fatty Acid Metabolism in Gastric Cancer[J]. Biomolecules, 2022, 12(5).[22] Lee D, Wada K, Taniguchi Y, et al. Expression of fatty acid binding protein 4 is involved in the cell growth of oral squamous cell carcinoma[J]. Oncol Rep, 2014, 31(3): 1116-20.[23] Tang Z, Shen Q, Xie H, et al. Elevated expression of FABP3 and FABP4 cooperatively correlates with poor prognosis in non-small cell lung cancer (NSCLC)[J]. Oncotarget, 2016, 7(29): 46253-46262.[24] Luo Y, Yang Z, Li D, et al. LDHB and FABP4 are Associated With Progression and Poor Prognosis of Pancreatic Ductal Adenocarcinomas[J]. Appl Immunohistochem Mol Morphol, 2017, 25(5): 351-357.[25] Huang M, Narita S, Inoue T, et al. Fatty acid binding protein 4 enhances prostate cancer progression by upregulating matrix metalloproteinases and stromal cell cytokine production[J]. Oncotarget, 2017, 8(67): 111780-111794.[26] Li G, Wu Q, Gong L, et al. FABP4 is an independent risk factor for lymph node metastasis and poor prognosis in patients with cervical cancer[J]. Cancer Cell International, 2021, 21(1): 1-15.