Review of role of fatty acid binding protein-4 in obesity-associated tumors

doi:10.3969/j.issn.1674-8115.2023.10.013

Abstract

Abstract:

Obesity is one of the major factors threatening human health. Excessive fat accumulation not only has detrimental effects on human metabolism and cardiovascular system, but also is highly correlated to the incidence and mortality of various tumors. Fatty acid binding protein-4 (FABP4) is a small molecule protein mainly expressed in adipocytes and macrophages, and is responsible for participating in fatty acid transport and lipid response. It has been found that FABP4 levels are not only associated with body fat content, but also aberrantly expressed in various obesity-associated tumor cells and tumor microenvironment, which is closely related to obesity-associated carcinogenesis, metastasis, recurrence and patient prognosis. Since FABP4 expression varies in different types of obesity-associated tumors, suggesting a complex role of FABP4 in tumorigenesis. Based on this, this article reviews different roles of FABP4 in multiple obesity-associated tumors.

Key words: fatty acid binding protein-4 (FABP4), obesity-associated tumor, adipocyte, adipocytokine, tumor microenvironment

CLC Number:

R730.23

WU Ruifang, FENG Ming, MENG Jian. Review of role of fatty acid binding protein-4 in obesity-associated tumors[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(10): 1311-1316.

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References 47

1	AMIRI M, YOUSEFNIA S, SEYED FOROOTAN F, et al. Diverse roles of fatty acid binding proteins (FABPs) in development and pathogenesis of cancers[J]. Gene, 2018, 676: 171-183.
2	STORCH J, THUMSER A E. Tissue-specific functions in the fatty acid-binding protein family[J]. J Biol Chem, 2010, 285(43): 32679-32683.
3	GARIN-SHKOLNIK T, RUDICH A, HOTAMISLIGIL G S, et al. FABP4 attenuates PPARγ and adipogenesis and is inversely correlated with PPARγ in adipose tissues[J]. Diabetes, 2014, 63(3): 900-911.
4	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.
5	DOU H X, WANG T, SU H X, et al. Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes[J]. Endocrine, 2020, 67(3): 587-596.
6	XU A M, WANG Y, XU J Y, et al. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome[J]. Clin Chem, 2006, 52(3): 405-413.
7	FURUHASHI M. Fatty acid-binding protein 4 in cardiovascular and metabolic diseases[J]. J Atheroscler Thromb, 2019, 26(3): 216-232.
8	SUN N, ZHAO X. Therapeutic implications of FABP4 in cancer: an emerging target to tackle cancer[J]. Front Pharmacol, 2022, 13: 948610.
9	CHEN X W, DING G, XU L, et al. A glimpse at the metabolic research in China[J]. Cell Metab, 2021, 33(11): 2122-2125.
10	CHENG C, ZHUO S M, ZHANG B, et al. Treatment implications of natural compounds targeting lipid metabolism in nonalcoholic fatty liver disease, obesity and cancer[J]. Int J Biol Sci, 2019, 15(8): 1654-1663.
11	AVGERINOS K I, SPYROU N, MANTZOROS C S, et al. Obesity and cancer risk: emerging biological mechanisms and perspectives[J]. Metabolism, 2019, 92: 121-135.
12	LIU S J, WU D, FAN Z Y, et al. FABP4 in obesity-associated carcinogenesis: novel insights into mechanisms and therapeutic implications[J]. Front Mol Biosci, 2022, 9: 973955.
13	PAVLOVA N N, ZHU J, THOMPSON C B. The hallmarks of cancer metabolism: still emerging[J]. Cell Metab, 2022, 34(3): 355-377.
14	MUKHERJEE A, BILECZ A J, LENGYEL E. The adipocyte microenvironment and cancer[J]. Cancer Metastasis Rev, 2022, 41(3): 575-587.
15	CABIA B, ANDRADE S, CARREIRA M C, et al. A role for novel adipose tissue-secreted factors in obesity-related carcinogenesis[J]. Obes Rev, 2016, 17(4): 361-376.
16	LHEUREUX S, GOURLEY C, VERGOTE I, et al. Epithelial ovarian cancer[J]. Lancet, 2019, 393(10177): 1240-1253.
17	KUROKI L, GUNTUPALLI S R. Treatment of epithelial ovarian cancer[J]. BMJ, 2020, 371: m3773.
18	NIEMAN K M, KENNY H A, PENICKA C V, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth[J]. Nat Med, 2011, 17(11): 1498-1503.
19	MUKHERJEE A, CHIANG C Y, DAIFOTIS H A, et al. Adipocyte-induced FABP4 expression in ovarian cancer cells promotes metastasis and mediates carboplatin resistance[J]. Cancer Res, 2020, 80(8): 1748-1761.
20	SANHUEZA S, SIMÓN L, CIFUENTES M, et al. The adipocyte-macrophage relationship in cancer: a potential target for antioxidant therapy[J]. Antioxidants (Basel), 2023, 12(1): 126.
21	YU C Y, NIU X L, DU Y R, et al. IL-17A promotes fatty acid uptake through the IL-17A/IL-17RA/p-STAT3/FABP4 axis to fuel ovarian cancer growth in an adipocyte-rich microenvironment[J]. Cancer Immunol Immunother, 2020, 69(1): 115-126.
22	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.
23	KIM S I, JUNG M, DAN K, et al. Proteomic discovery of biomarkers to predict prognosis of high-grade serous ovarian carcinoma[J]. Cancers (Basel), 2020, 12(4): 790.
24	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.
25	HANCKE K, GRUBECK D, HAUSER N, et al. Adipocyte fatty acid-binding protein as a novel prognostic factor in obese breast cancer patients[J]. Breast Cancer Res Treat, 2010, 119(2): 367-377.
26	HAO J Q, ZHANG Y W, YAN X F, et al. Circulating adipose fatty acid binding protein is a new link underlying obesity-associated breast/mammary tumor development[J]. Cell Metab, 2018, 28(5): 689-705.e5.
27	KIM H M, LEE Y K, KIM E S, et al. Energy transfer from adipocytes to cancer cells in breast cancer[J]. Neoplasma, 2020, 67(5): 992-1001.
28	WANG J C, LI Y S. CD36 tango in cancer: signaling pathways and functions[J]. Theranostics, 2019, 9(17): 4893-4908.
29	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.
30	LIU Z, GAO Z J, LI B, et al. Lipid-associated macrophages in the tumor-adipose microenvironment facilitate breast cancer progression[J]. Oncoimmunology, 2022, 11(1): 2085432.
31	POYNTER J N, RICHARDSON M, BLAIR C K, et al. Obesity over the life course and risk of acute myeloid leukemia and myelodysplastic syndromes[J]. Cancer Epidemiol, 2016, 40: 134-140.
32	SHAFAT M S, OELLERICH T, MOHR S, et al. Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment[J]. Blood, 2017, 129(10): 1320-1332.
33	TABE Y, YAMAMOTO S, SAITOH K, et al. Bone marrow adipocytes facilitate fatty acid oxidation activating AMPK and a transcriptional network supporting survival of acute monocytic leukemia cells[J]. Cancer Res, 2017, 77(6): 1453-1464.
34	SHEN N, YAN F, PANG J X, et al. A nucleolin-DNMT1 regulatory axis in acute myeloid leukemogenesis[J]. Oncotarget, 2014, 5(14): 5494-5509.
35	GARZON R, LIU S J, FABBRI M, et al. MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1[J]. Blood, 2009, 113(25): 6411-6418.
36	PRADA-ARISMENDY J, ARROYAVE J C, RÖTHLISBERGER S. Molecular biomarkers in acute myeloid leukemia[J]. Blood Rev, 2017, 31(1): 63-76.
37	YAN F, SHEN N, PANG J X, et al. Fatty acid-binding protein FABP4 mechanistically links obesity with aggressive AML by enhancing aberrant DNA methylation in AML cells[J]. Leukemia, 2017, 31(6): 1434-1442.
38	YAN F, SHEN N, PANG J X, et al. A vicious loop of fatty acid-binding protein 4 and DNA methyltransferase 1 promotes acute myeloid leukemia and acts as a therapeutic target[J]. Leukemia, 2018, 32(4): 865-873.
39	MCGLYNN K A, PETRICK J L, EL-SERAG H B. Epidemiology of hepatocellular carcinoma[J]. Hepatology, 2021, 73(Suppl 1): 4-13.
40	THOMPSON K J, AUSTIN R G, NAZARI S S, et al. Altered fatty acid-binding protein 4 (FABP4) expression and function in human and animal models of hepatocellular carcinoma[J]. Liver Int, 2018, 38(6): 1074-1083.
41	YANG H R, DENG Q M, NI T, et al. Targeted inhibition of LPL/FABP4/CPT1 fatty acid metabolic axis can effectively prevent the progression of nonalcoholic steatohepatitis to liver cancer[J]. Int J Biol Sci, 2021, 17(15): 4207-4222.
42	ZHONG C Q, ZHANG X P, MA N, et al. FABP4 suppresses proliferation and invasion of hepatocellular carcinoma cells and predicts a poor prognosis for hepatocellular carcinoma[J]. Cancer Med, 2018, 7(6): 2629-2640.
43	ADESUNLOYE B A. Mechanistic insights into the link between obesity and prostate cancer[J]. Int J Mol Sci, 2021, 22(8): 3935.
44	GÖBEL A, DELL'ENDICE S, JASCHKE N, et al. The role of inflammation in breast and prostate cancer metastasis to bone[J]. Int J Mol Sci, 2021, 22(10): 5078.
45	HERROON M K, RAJAGURUBANDARA E, HARDAWAY A L, et al. Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms[J]. Oncotarget, 2013, 4(11): 2108-2123.
46	UEHARA H, TAKAHASHI T, OHA M, et al. Exogenous fatty acid binding protein 4 promotes human prostate cancer cell progression[J]. Int J Cancer, 2014, 135(11): 2558-2568.
47	HOTAMISLIGIL G S, BERNLOHR D A. Metabolic functions of FABPs: mechanisms and therapeutic implications[J]. Nat Rev Endocrinol, 2015, 11(10): 592-605.

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