中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 3
Mar.  2022
Turn off MathJax
Article Contents

Role of lysyl oxidase family in the development and progression of hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2022.03.039
Research funding:

Research funding: National Natural Science Foundation of China (81960841);

General Project of National Natural Science Foundation of China (82060848);

Natural Science Foundation of Guangxi Province (2018GXNSFAA281096);

Innovation Project of General Postgraduates in Guangxi University of Traditional Chinese Medicine (YCXJ2021039)

More Information
  • Corresponding author: MAO Dewen, mdwboshi2005@163.com(ORCID: 0000-0001-9438-9325)
  • Received Date: 2021-07-29
  • Accepted Date: 2021-10-11
  • Published Date: 2022-03-20
  • Lysyl oxidase (LOX) family is a group of copper-containing amine oxidases composed of LOX and LOX-like proteins (LOXL1, LOXL2, LOXL3, and LOXL4). It is overexpressed in tumor tissue and promotes tumor metastasis through covalent cross-linking of extracellular matrix, with the functions of cell growth control, tumor inhibition, senescence, and chemotaxis. In recent years, more and more evidence has shown that LOX family members play a key role in the pathogenesis of hepatocellular carcinoma (HCC), suggesting that they have great potential as therapeutic targets. This article reviews the role of LOX family members in the development and progression of HCC and the intervention effect of traditional Chinese medicine extracts on HCC by regulating LOX family, in order to provide a reference for further research on the prevention and treatment of HCC.

     

  • loading
  • [1]
    Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association; Professional Committee for Hepatology, Chinese Research Hospital Association; Chinese Society of Hepatology, Chinese Medical Association, et al. Guideline for stratified screening and surveillance of primary liver cancer (2020 edition)[J]. J Clin Hepatol, 2021, 37(2): 286-295. DOI: 10.3969/j.issn.1001-5256.2021.02.009.

    中华预防医学会肝胆胰疾病预防与控制专业委员会, 中国研究型医院学会肝病专业委员会, 中华医学会肝病学分会, 等. 原发性肝癌的分层筛查与监测指南(2020版)[J]. 临床肝胆病杂志, 2021, 37(2): 286-295. DOI: 10.3969/j.issn.1001-5256.2021.02.009.
    [2]
    VANNUCCI L. Stroma as an active player in the development of the tumor microenvironment[J]. Cancer Microenviron, 2015, 8(3): 159-166. DOI: 10.1007/s12307-014-0150-x.
    [3]
    PINNELL SR, MARTIN GR. The cross-linking of collagen and elastin: Enzymatic conversion of lysine in peptide linkage to alpha-aminoadipic-delta-semialdehyde (allysine) by an extract from bone[J]. Proc Natl Acad Sci U S A, 1968, 61(2): 708-716. DOI: 10.1073/pnas.61.2.708.
    [4]
    TENTI P, VANNUCCI L. Lysyl oxidases: Linking structures and immunity in the tumor microenvironment[J]. Cancer Immunol Immunother, 2020, 69(2): 223-235. DOI: 10.1007/s00262-019-02404-x.
    [5]
    JUNG ST, KIM MS, SEO JY, et al. Purification of enzymatically active human lysyl oxidase and lysyl oxidase-like protein from Escherichia coli inclusion bodies[J]. Protein Expr Purif, 2003, 31(2): 240-246. DOI: 10.1016/s1046-5928(03)00217-1.
    [6]
    GRIMSBY JL, LUCERO HA, TRACKMAN PC, et al. Role of lysyl oxidase propeptide in secretion and enzyme activity[J]. J Cell Biochem, 2010, 111(5): 1231-1243. DOI: 10.1002/jcb.22845.
    [7]
    MOLNAR J, FONG KS, HE QP, et al. Structural and functional diversity of lysyl oxidase and the LOX-like proteins[J]. Biochim Biophys Acta, 2003, 1647(1-2): 220-224. DOI: 10.1016/s1570-9639(03)00053-0.
    [8]
    WATERHOUSE A, BERTONI M, BIENERT S, et al. SWISS-MODEL: Homology modelling of protein structures and complexes[J]. Nucleic Acids Res, 2018, 46(W1): w296-w303. DOI: 10.1093/nar/gky427.
    [9]
    BIENERT S, WATERHOUSE A, de BEER TA, et al. The SWISS-MODEL Repository-new features and functionality[J]. Nucleic Acids Res, 2017, 45(D1): d313-d319. DOI: 10.1093/nar/gkw1132.
    [10]
    GUEX N, PEITSCH MC, SCHWEDE T. Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective[J]. Electrophoresis, 2009, 30 Suppl 1: s162-s173. DOI: 10.1002/elps.200900140.
    [11]
    STUDER G, REMPFER C, WATERHOUSE AM, et al. QMEANDisCo-distance constraints applied on model quality estimation[J]. Bioinformatics, 2020, 36(6): 1765-1771. DOI: 10.1093/bioinformatics/btz828.
    [12]
    BERTONI M, KIEFER F, BIASINI M, et al. Modeling protein quaternary structure of homo-and hetero-oligomers beyond binary interactions by homology[J]. Sci Rep, 2017, 7(1): 10480. DOI: 10.1038/s41598-017-09654-8.
    [13]
    ZHU J, HUANG S, WU G, et al. Lysyl oxidase is predictive of unfavorable outcomes and essential for regulation of vascular endothelial growth factor in hepatocellular carcinoma[J]. Dig Dis Sci, 2015, 60(10): 3019-3031. DOI: 10.1007/s10620-015-3734-5.
    [14]
    SALGADO R, BENOY I, BOGERS J, et al. Platelets and vascular endothelial growth factor (VEGF): A morphological and functional study[J]. Angiogenesis, 2001, 4(1): 37-43. DOI: 10.1023/a:1016611230747.
    [15]
    DONG Y, XIE X, WANG Z, et al. Increasing matrix stiffness upregulates vascular endothelial growth factor expression in hepatocellular carcinoma cells mediated by integrin β1[J]. Biochem Biophys Res Commun, 2014, 444(3): 427-432. DOI: 10.1016/j.bbrc.2014.01.079.
    [16]
    WANG Y, ZHANG X, WANG W, et al. Integrin αVβ5/Akt/Sp1 pathway participates in matrix stiffness-mediated effects on VEGFR2 upregulation in vascular endothelial cells[J]. Am J Cancer Res, 2020, 10(8): 2635-2648.
    [17]
    YUAN R, LI Y, YANG B, et al. LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis in ICC[J]. Mol Ther Nucleic Acids, 2021, 23: 797-810. DOI: 10.1016/j.omtn.2021.01.001.
    [18]
    FAN Z, ZHENG W, LI H, et al. LOXL2 upregulates hypoxia-inducible factor-1α signaling through Snail-FBP1 axis in hepatocellular carcinoma cells[J]. Oncol Rep, 2020, 43(5): 1641-1649. DOI: 10.3892/or.2020.7541.
    [19]
    UMANA-DIAZ C, PICHOL-THIEVEND C, MARCHAND MF, et al. Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Like2 regulate endothelial ECM and angiogenesis through non-catalytic scaffolding mechanisms[J]. Matrix Biol, 2020, 88: 33-52. DOI: 10.1016/j.matbio.2019.11.003.
    [20]
    LI R, WANG Y, ZHANG X, et al. Exosome-mediated secretion of LOXL4 promotes hepatocellular carcinoma cell invasion and metastasis[J]. Mol Cancer, 2019, 18(1): 18. DOI: 10.1186/s12943-019-0948-8.
    [21]
    YAN L, XU F, DAI CL. Relationship between epithelial-to-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma[J]. J Exp Clin Cancer Res, 2018, 37(1): 203. DOI: 10.1186/s13046-018-0887-z.
    [22]
    HAPKE RY, HAAKE SM. Hypoxia-induced epithelial to mesenchymal transition in cancer[J]. Cancer Lett, 2020, 487: 10-20. DOI: 10.1016/j.canlet.2020.05.012.
    [23]
    UMEZAKI N, NAKAGAWA S, YAMASHITA YI, et al. Lysyl oxidase induces epithelial-mesenchymal transition and predicts intrahepatic metastasis of hepatocellular carcinoma[J]. Cancer Sci, 2019, 110(6): 2033-2043. DOI: 10.1111/cas.14010.
    [24]
    WANG M, ZHAO X, ZHU D, et al. HIF-1α promoted vasculogenic mimicry formation in hepatocellular carcinoma through LOXL2 up-regulation in hypoxic tumor microenvironment[J]. J Exp Clin Cancer Res, 2017, 36(1): 60. DOI: 10.1186/s13046-017-0533-1.
    [25]
    CUEVAS EP, MORENO-BUENO G, CANESIN G, et al. LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition[J]. Biol Open, 2014, 3(2): 129-137. DOI: 10.1242/bio.20146841.
    [26]
    HU Q, MASUDA T, KURAMITSU S, et al. Potential association of LOXL1 with peritoneal dissemination in gastric cancer possibly via promotion of EMT[J]. PLoS One, 2020, 15(10): e0241140. DOI: 10.1371/journal.pone.0241140.
    [27]
    LAURENTINO TS, SOARES R, MARIE S, et al. LOXL3 function beyond amino oxidase and role in pathologies, including cancer[J]. Int J Mol Sci, 2019, 20(14): 3587. DOI: 10.3390/ijms20143587.
    [28]
    WU Y, GE G. Complexity of type Ⅳ collagens: From network assembly to function[J]. Biol Chem, 2019, 400(5): 565-574. DOI: 10.1515/hsz-2018-0317.
    [29]
    FANG M, PENG CW, YUAN JP, et al. Coevolution of the tumor microenvironment revealed by quantum dot-based multiplexed imaging of hepatocellular carcinoma[J]. Future Oncol, 2013, 9(7): 1029-1037. DOI: 10.2217/fon.13.63.
    [30]
    WONG CC, TSE AP, HUANG YP, et al. Lysyl oxidase-like 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma[J]. Hepatology, 2014, 60(5): 1645-1658. DOI: 10.1002/hep.27320.
    [31]
    BARKER HE, BIRD D, LANG G, et al. Tumor-secreted LOXL2 activates fibroblasts through FAK signaling[J]. Mol Cancer Res, 2013, 11(11): 1425-1436. DOI: 10.1158/1541-7786.MCR-13-0033-T.
    [32]
    XING X, WANG Y, ZHANG X, et al. Matrix stiffness-mediated effects on macrophages polarization and their LOXL2 expression[J]. FEBS J, 2021, 288(11): 3465-3477. DOI: 10.1111/febs.15566.
    [33]
    TAN HY, WANG N, ZHANG C, et al. Lysyl oxidase-like 4 fosters an immunosuppressive microenvironment during hepatocarcinogenesis[J]. Hepatology, 2021, 73(6): 2326-2341. DOI: 10.1002/hep.31600.
    [34]
    BUSNADIEGO O, GONZÁLEZ-SANTAMARÍA J, LAGARES D, et al. LOXL4 is induced by transforming growth factor β1 through Smad and JunB/Fra2 and contributes to vascular matrix remodeling[J]. Mol Cell Biol, 2013, 33(12): 2388-2401. DOI: 10.1128/MCB.00036-13.
    [35]
    CONTENTE S, KENYON K, SRIRAMAN P, et al. Epigenetic inhibition of lysyl oxidase transcription after transformation by ras oncogene[J]. Mol Cell Biochem, 1999, 194(1-2): 79-91. DOI: 10.1023/a:1006913122261.
    [36]
    CSISZAR K, FONG SF, UJFALUSI A, et al. Somatic mutations of the lysyl oxidase gene on chromosome 5q23.1 in colorectal tumors[J]. Int J Cancer, 2002, 97(5): 636-642. DOI: 10.1002/ijc.10035.
    [37]
    KANEDA A, WAKAZONO K, TSUKAMOTO T, et al. Lysyl oxidase is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in human gastric cancers[J]. Cancer Res, 2004, 64(18): 6410-6415. DOI: 10.1158/0008-5472.CAN-04-1543.
    [38]
    NILSSON M, ADAMO H, BERGH A, et al. Inhibition of lysyl oxidase and lysyl oxidase-like enzymes has tumour-promoting and tumour-suppressing roles in experimental prostate cancer[J]. Sci Rep, 2016, 6: 19608. DOI: 10.1038/srep19608.
    [39]
    ZHENG Y, WANG X, WANG H, et al. Expression of the lysyl oxidase propeptide in hepatocellular carcinoma and its clinical relevance[J]. Oncol Rep, 2014, 31(4): 1669-1676. DOI: 10.3892/or.2014.3044.
    [40]
    NARESHKUMAR RN, SULOCHANA KN, CORAL K. Inhibition of angiogenesis in endothelial cells by Human Lysyl oxidase propeptide[J]. Sci Rep, 2018, 8(1): 10426. DOI: 10.1038/s41598-018-28745-8.
    [41]
    WU G, GUO Z, CHANG X, et al. LOXL1 and LOXL4 are epigenetically silenced and can inhibit ras/extracellular signal-regulated kinase signaling pathway in human bladder cancer[J]. Cancer Res, 2007, 67(9): 4123-4129. DOI: 10.1158/0008-5472.CAN-07-0012.
    [42]
    CHOI SK, KIM HS, JIN T, et al. LOXL4 knockdown enhances tumor growth and lung metastasis through collagen-dependent extracellular matrix changes in triple-negative breast cancer[J]. Oncotarget, 2017, 8(7): 11977-11989. DOI: 10.18632/oncotarget.14450.
    [43]
    JOERGER AC, FERSHT AR. The p53 pathway: Origins, inactivation in cancer, and emerging therapeutic approaches[J]. Annu Rev Biochem, 2016, 85: 375-404. DOI: 10.1146/annurev-biochem-060815-014710.
    [44]
    SHAO J, LU J, ZHU W, et al. Derepression of LOXL4 inhibits liver cancer growth by reactivating compromised p53[J]. Cell Death Differ, 2019, 26(11): 2237-2252. DOI: 10.1038/s41418-019-0293-x.
    [45]
    BIE B, SUN J, GUO Y, et al. Baicalein: A review of its anti-cancer effects and mechanisms in Hepatocellular Carcinoma[J]. Biomed Pharmacother, 2017, 93: 1285-1291. DOI: 10.1016/j.biopha.2017.07.068.
    [46]
    NGUYEN LT, SONG YW, CHO SK. Baicalein inhibits epithelial to mesenchymal transition via downregulation of Cyr61 and LOXL-2 in MDA-MB231 breast cancer cells[J]. Mol Cells, 2016, 39(12): 909-914. DOI: 10.14348/molcells.2016.0243.
    [47]
    LI X, LI J, WANG L, et al. The role of metformin and resveratrol in the prevention of hypoxia-inducible factor 1α accumulation and fibrosis in hypoxic adipose tissue[J]. Br J Pharmacol, 2016, 173(12): 2001-2015. DOI: 10.1111/bph.13493.
    [48]
    MOHSENI R, ARAB SADEGHABADI Z, GOODARZI MT, et al. Co-administration of resveratrol and beta-aminopropionitrile attenuates liver fibrosis development via targeting lysyl oxidase in CCl4-induced liver fibrosis in rats[J]. Immunopharmacol Immunotoxicol, 2019, 41(6): 644-651. DOI: 10.1080/08923973.2019.1688829.
    [49]
    LU L, LIU S, DONG Q, et al. Salidroside suppresses the metastasis of hepatocellular carcinoma cells by inhibiting the activation of the Notch1 signaling pathway[J]. Mol Med Rep, 2019, 19(6): 4964-4972. DOI: 10.3892/mmr.2019.10115.
    [50]
    QIN Y, LIU HJ, LI M, et al. Salidroside improves the hypoxic tumor microenvironment and reverses the drug resistance of platinum drugs via HIF-1α signaling pathway[J]. EBioMedicine, 2018, 38: 25-36. DOI: 10.1016/j.ebiom.2018.10.069.
    [51]
    HU Q, YOU SP, LIU T, et al. An investigation on the anti-liver cancer effect of cistanche[J]. Carcinog Teratogenesis Mutagen, 2018, 30(3): 194-199. DOI: 10.3969/j.issn.1004-616x.2018.03.006.

    胡琼, 由淑萍, 刘涛, 等. 肉苁蓉苯乙醇总苷抗肝癌作用的实验研究[J]. 癌变·畸变·突变, 2018, 30(3): 194-199. DOI: 10.3969/j.issn.1004-616x.2018.03.006.
    [52]
    WEN L, HU J, ZHANG J, et al. Phenylethanol glycosides from Herba Cistanche improve the hypoxic tumor microenvironment and enhance the effects of oxaliplatin via the HIF-1α signaling pathway[J]. Mol Med Rep, 2021, 24(1): 517. DOI: 10.3892/mmr.2021.12156.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(5)  / Tables(1)

    Article Metrics

    Article views (891) PDF downloads(70) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return