Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 + 2764 word(s) 2764 2020-12-31 08:01:44 |
2 format correct + 436 word(s) 3200 2021-01-07 05:13:14 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Lin, H. Lysyl Oxidase. Encyclopedia. Available online: (accessed on 25 June 2024).
Lin H. Lysyl Oxidase. Encyclopedia. Available at: Accessed June 25, 2024.
Lin, Hung-Yu. "Lysyl Oxidase" Encyclopedia, (accessed June 25, 2024).
Lin, H. (2021, January 06). Lysyl Oxidase. In Encyclopedia.
Lin, Hung-Yu. "Lysyl Oxidase." Encyclopedia. Web. 06 January, 2021.
Lysyl Oxidase

The lysyl oxidase (LOX) family members are secreted copper-dependent amine oxidases, comprised of five paralogues: LOX and LOX-like l-4 (LOXL1-4), which are characterized by catalytic activity contributing to the remodeling of the cross-linking of the structural extracellular matrix (ECM). ECM remodeling plays a key role in the angiogenesis surrounding tumors, whereby a corrupt tumor microenvironment (TME) takes shape. Primary liver cancer includes hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), ranked as the seventh most common cancer globally, with limited therapeutic options for advanced stages. In recent years, a growing body of evidence has revealed the key roles of LOX family members in the pathogenesis of liver cancer and the shaping of TME, indicating their notable potential as therapeutic targets.

liver cancer hepatocellular carcinoma cholangiocarcinoma lysyl oxidase family members tumor microenvironment

1. Introduction

The lysyl oxidase (LOX) family members are secreted copper-dependent amine oxidases, comprised of five paralogues: LOX and LOX-like l-4 (LOXL1-4) [1]. As shown in Figure 1, LOX family members encoded by the human LOX/LOXLs genes are located at various chromosome sites, including 5q23.1, 15q24.1, 8p21.3, 2p13.1, and 10q24.2 [2][3]. These members structurally consist of a variable N-terminal domain and a highly conserved C-terminal domain (Figure 1). The conserved C- terminal consists of copper binding domain amino acid residues forming lysine tryosylquinone (LTQ), and a cytokine receptor-like (CRL) domain [4]. In the N-terminal domain, LOX and LOXL1 possess a propeptide sequence, whereas LOXL2–4 present four scavenger-receptor cysteine-rich (SRCR) domains in this region [5]. The matured active forms of LOX and LOXL1 are formed by a cleavage process executed by bone morphogenetic protein 1 (BMP-1), which is not a required program for LOXL2, LOXL3, or LOXL4 [6] (Figure 1). LOX family members are characterized by their catalytic activity contributing to structural integrity and increased tensile strength, acting to remodel the cross-linking of the structural extracellular matrix (ECM) of fibrotic organs such as the liver [7][8][9][10], as well as that of the cancer microenvironments [2][4]. A growing body of evidence indicates that the expression of LOX family members increases in invasive and metastatic cancers, and their elevated expression correlates with poor survival [11][12][13]. Their crucial role in tumor proliferation, epithelial–mesenchymal transition (EMT), migration, invasion, formation of pre-metastatic niches, and immunomodulation have been well documented [11][14][15][16][17]. Consistent with these reports, we note that a genomic big data-centric pathway activity analysis reveals their role in the activation of the EMT pathway in cancer (Figure 2).

Figure 1. The structure of lysyl oxidase (LOX) family members. LOX family members encoded by the human LOX/LOXLs genes are located at various chromosome sites, including 5q23.1, 15q24.1, 8p21.3, 2p13.1, and 10q24.2. These members consist of a variable N-terminal domain and a highly conserved C-terminal domain. Sig, signal peptide (Sig); copper binding domain (Cu); lysyl-tyrosyl-quinone (LTQ) co-factor; scavenger receptor cysteine-rich (SRCR) domain; cytokine receptor-like (CRL) domain.

Figure 2. The epithelial–mesenchymal transition (EMT) pathway is activated by LOX, LOXL1, LOXL2, LOXL3, and LOXL4 in genomic big data-centric pathway analysis. Heatmap data demonstrated that LOX, LOXL1, LOXL2, LOXL3, and LOXL4 have activating/inhibiting (red/blue) functions on each cancer-related pathway. Note that LOX, LOXL1, LOXL2, LOXL3, and LOXL4 account for 54%, 47%, 44%, 44%, and 25% of cancers in the EMT-activating pathway, respectively. The pathway activity module was assessed with the GSCALite web server. High-throughput antibody-based technique reverse phase protein array (RPPA) was conduct to determine the expression of The Cancer Genome Atlas (TCGA) samples of at least 5 cancer types. Known cancer-related pathways are included: TSC/mTOR, RTK, RAS/MAPK, PI3K/AKT, hormone ER, hormone AR, EMT, DNA damage response, cell cycle, apoptosis.

Primary liver cancer is ranked as the seventh most common cancer globally, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) [18]. HCC accounts for approximately 90%, while CCA and the combination of HCC and CCA account for 10% of liver cancers [19]. HCC features hepatocellular characteristics at the morphological and molecular levels, whereas CCA exhibits biliary epithelial cell properties. Of note, limited therapeutic options are currently available for the advanced stages of liver cancers. Furthermore, as estimated by the World Health Organization (WHO), more than one million patients are projected to die from liver cancer in the next decade [20]. Growing evidence supports the role of the tumor microenvironment (TME) in the development and progression of HCC. The TME is composed of cellular and non-cellular components. Cellular components include angiogenic endothelial cells, immune system cells, tumor-associated fibroblasts (TAF), and tumor-associated macrophage (TAM); while non-cellular components involve ECM, exosomes, soluble cytokines, and signaling molecules [21].

Mounting evidence in recent years has revealed the key roles of LOX family members in the pathogenesis of liver cancer. Their ECM-remodeling and secretable nature permits the shaping of TME in both the primary organ and distal metastatic sites. More importantly, their potential as therapeutic targets is notably emerging. This expeditious progress prompted us to summarize the prognostic significance of such research, and to review the novel biological roles of LOX family members in tumor cells and the TME of liver cancer. Furthermore, we highlight recent insights into their mechanisms and potential for target therapy approaches.


  1. Barker, H.E.; Cox, T.R.; Erler, J.T. The rationale for targeting the LOX family in cancer. Nat. Rev. Cancer 2012, 12, 540–552.
  2. Ye, M.; Song, Y.; Pan, S.; Chu, M.; Wang, Z.-W.; Zhu, X. Evolving roles of lysyl oxidase family in tumorigenesis and cancer therapy. Pharmacol. Ther. 2020, 215, 107633.
  3. López, B.; González, A.; Hermida, N.; Valencia, F.; De Teresa, E.; Díez, J. Role of lysyl oxidase in myocardial fibrosis: From basic science to clinical aspects. Am. J. Physiol. Circ. Physiol. 2010, 299, H1–H9.
  4. Wang, T.-H.; Hsia, S.-M.; Shieh, T.-M. Lysyl Oxidase and the Tumor Microenvironment. Int. J. Mol. Sci. 2016, 18, 62.
  5. Xiao, Q.; Ge, G. Lysyl Oxidase, Extracellular Matrix Remodeling and Cancer Metastasis. Cancer Microenviron. 2012, 5, 261–273.
  6. Borel, A.; Eichenberger, D.; Farjanel, J.; Kessler, E.; Gleyzal, C.; Hulmes, D.J.S.; Sommer, P.; Font, B. Lysyl Oxidase-like Protein from Bovine Aorta. Isolation and maturation to an active form by bone morphogenetic protein-1. J. Biol. Chem. 2001, 276, 48944–48949.
  7. Zhao, W.; Yang, A.; Chen, W.; Wang, P.; Liu, T.; Cong, M.; Xu, A.; Yan, X.; Jia, J.; You, H. Inhibition of lysyl oxidase-like 1 (LOXL1) expression arrests liver fibrosis progression in cirrhosis by reducing elastin crosslinking. Biochim. Biophys. Acta (BBA) Mol. Basis Dis. 2018, 1864, 1129–1137.
  8. Ikenaga, N.; Peng, Z.-W.; Vaid, K.A.; Liu, S.B.; Yoshida, S.; Sverdlov, D.Y.; Mikels-Vigdal, A.; Smith, V.; Schuppan, D.; Popov, Y.V. Selective targeting of lysyl oxidase-like 2 (LOXL2) suppresses hepatic fibrosis progression and accelerates its reversal. Gut 2017, 66, 1697–1708.
  9. Dongiovanni, P.; Meroni, M.; Baselli, G.A.; Bassani, G.A.; Rametta, R.; Pietrelli, A.; Maggioni, M.; Facciotti, F.; Trunzo, V.; Badiali, S.; et al. Insulin resistance promotes Lysyl Oxidase Like 2 induction and fibrosis accumulation in non-alcoholic fatty liver disease. Clin. Sci. 2017, 131, 1301–1315.
  10. Aumiller, V.; Strobel, B.; Romeike, M.; Schuler, M.; Stierstorfer, B.E.; Kreuz, S. Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis. Sci. Rep. 2017, 7, 1–13.
  11. Miller, B.W.; Morton, J.P.; Pinese, M.; Saturno, G.; Jamieson, N.B.; McGhee, E.; Timpson, P.; Leach, J.; McGarry, L.; Shanks, E.; et al. Targeting the LOX / hypoxia axis reverses many of the features that make pancreatic cancer deadly: Inhibition of LOX abrogates metastasis and enhances drug efficacy. EMBO Mol. Med. 2015, 7, 1063–1076.
  12. Wilgus, M.-L.; Borczuk, A.C.; Stoopler, M.; Ginsburg, M.; Gorenstein, L.; Sonett, J.R.; Powell, C.A. Lysyl oxidase: A lung adenocarcinoma biomarker of invasion and survival. Cancer 2010, 117, 2186–2191.
  13. Erler, J.T.; Bennewith, K.L.; Nicolau, M.; Dornhöfer, N.; Kong, C.; Le, Q.-T.; Chi, J.-T.A.; Jeffrey, S.S.; Giaccia, A.J. Lysyl oxidase is essential for hypoxia-induced metastasis. Nat. Cell Biol. 2006, 440, 1222–1226.
  14. Tenti, P.; Vannucci, L. Lysyl oxidases: Linking structures and immunity in the tumor microenvironment. Cancer Immunol. Immunother. 2019, 69, 223–235.
  15. Tan, H.Y.; Wang, N.; Zhang, C.; Chan, Y.T.; Yuen, M.F.; Feng, Y. LOXL4 Fosters an Immunosuppressive Microenvironment During Hepatocarcinogenesis. Hepatology 2020.
  16. Kasashima, H.; Yashiro, M.; Kinoshita, H.; Fukuoka, T.; Morisaki, T.; Masuda, G.; Sakurai, K.; Kubo, N.; Ohira, M.; Hirakawa, K. Lysyl oxidase is associated with the epithelial–mesenchymal transition of gastric cancer cells in hypoxia. Gastric Cancer 2016, 19, 431–442.
  17. Levental, K.R.; Yu, H.; Kass, L.; Lakins, J.N.; Egeblad, M.; Erler, J.T.; Fong, S.F.; Csiszar, K.; Giaccia, A.; Weninger, W.; et al. Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling. Cell 2009, 139, 891–906.
  18. Global Burden of Disease Cancer Collaboration; Fitzmaurice, C.; Abate, D.; Abbasi, N.; Abbastabar, H.; Abd-Allah, F.; Abdel-Rahman, O.; Abdelalim, A.; Abdoli, A.; Abdollahpour, I.; et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2019, 5, 1749–1768.
  19. Nault, J.; Bioulac–Sage, P.; Zucman–Rossi, J. Hepatocellular Benign Tumors—From Molecular Classification to Personalized Clinical Care. Gastroenterology 2013, 144, 888–902.
  20. World Health Organization. Projections of Mortality and Causes of Death, 2016 to 2060. Available online: (accessed on 4 November 2020).
  21. Tahmasebi-Birgani, M.; Carloni, V. Tumor Microenvironment, a Paradigm in Hepatocellular Carcinoma Progression and Therapy. Int. J. Mol. Sci. 2017, 18, 405.
  22. Zhu, J.; Huang, S.; Wu, G.; Huang, C.; Li, X.; Chen, Z.; Zhao, L.; Zhao, Y. Lysyl Oxidase Is Predictive of Unfavorable Outcomes and Essential for Regulation of Vascular Endothelial Growth Factor in Hepatocellular Carcinoma. Dig. Dis. Sci. 2015, 60, 3019–3031.
  23. Yang, M.; Liu, J.; Wang, F.; Tian, Z.; Ma, B.; Li, Z.; Wang, B.; Zhao, W. Lysyl oxidase assists tumor-initiating cells to enhance angiogenesis in hepatocellular carcinoma. Int. J. Oncol. 2019, 54, 1398–1408.
  24. Umezaki, N.; Nakagawa, S.; Yamashita, Y.; Kitano, Y.; Arima, K.; Miyata, T.; Hiyoshi, Y.; Okabe, H.; Nitta, H.; Hayashi, H.; et al. Lysyl oxidase induces epithelial-mesenchymal transition and predicts intrahepatic metastasis of hepatocellular carcinoma. Cancer Sci. 2019, 110, 2033–2043.
  25. Erler, J.T.; Giaccia, A.J. Lysyl Oxidase Mediates Hypoxic Control of Metastasis: Figure 1. Cancer Res. 2006, 66, 10238–10241.
  26. Triantafyllou, E.-A.; Mylonis, I.; Simos, G.; Paraskeva, E. Hypoxia Induces Pro-Fibrotic and Fibrosis Marker Genes in Hepatocellular Carcinoma Cells Independently of Inflammatory Stimulation and the NF-κΒ Pathway. Hypoxia 2019, 7, 87–91.
  27. Wang, V.; Davis, D.A.; Yarchoan, R. Identification of functional hypoxia inducible factor response elements in the human lysyl oxidase gene promoter. Biochem. Biophys. Res. Commun. 2017, 490, 480–485.
  28. Wang, V.; Davis, D.A.; Haque, M.; Huang, L.E.; Yarchoan, R. Differential Gene Up-Regulation by Hypoxia-Inducible Factor-1α and Hypoxia-Inducible Factor-2α in HEK293T Cells. Cancer Res. 2005, 65, 3299–3306.
  29. Tse, A.P.-W.; Sze, K.M.-F.; Shea, Q.T.-K.; Chiu, E.Y.-T.; Tsang, F.H.-C.; Chiu, D.K.-C.; Zhang, M.S.; Lee, D.; Xu, I.M.-J.; Chan, C.Y.-K.; et al. Hepatitis transactivator protein X promotes extracellular matrix modification through HIF/LOX pathway in liver cancer. Oncogenesis 2018, 7, 44.
  30. Huang, C.-S.; Ho, C.-T.; Tu, S.-H.; Pan, M.-H.; Chang, H.-W.; Wu, C.-H.; Ho, Y.-S.; Chang, C.-H.; Chuang, C.-H. Long-Term Ethanol Exposure-Induced Hepatocellular Carcinoma Cell Migration and Invasion through Lysyl Oxidase Activation Are Attenuated by Combined Treatment with Pterostilbene and Curcumin Analogues. J. Agric. Food Chem. 2013, 61, 4326–4335.
  31. Zheng, Y.; Wang, X.; Wang, H.; Yan, W.; Zhang, Q.; Chang, X. Expression of the lysyl oxidase propeptide in hepatocellular carcinoma and its clinical relevance. Oncol. Rep. 2014, 31, 1669–1676.
  32. Chakraborty, S.; Njah, K.; Hong, W. Agrin Mediates Angiogenesis in the Tumor Microenvironment. Trends Cancer 2020, 6, 81–85.
  33. Hecht, J.R.; Benson, A.B.; Vyushkov, D.; Yang, Y.; Bendell, J.; Verma, U. A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab in Combination with FOLFIRI for the Second-Line Treatment of Metastatic KRAS Mutant Colorectal Adenocarcinoma. Oncologist 2017, 22, 243.
  34. Benson, A.B.; Wainberg, Z.A.; Hecht, J.R.; Vyushkov, D.; Dong, H.; Bendell, J.; Kudrik, F. A Phase II Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab or Placebo in Combination with Gemcitabine for the First-Line Treatment of Pancreatic Adenocarcinoma. Oncologist 2017, 22, 241.
  35. Bondareva, A.; Downey, C.M.; Ayres, F.; Liu, W.; Boyd, S.K.; Hallgrímsson, B.; Jirik, F.R. The Lysyl Oxidase Inhibitor, β-Aminopropionitrile, Diminishes the Metastatic Colonization Potential of Circulating Breast Cancer Cells. PLoS ONE 2009, 4, e5620.
  36. Yang, X.; Li, S.; Li, W.; Chen, J.; Xiao, X.; Wang, Y.; Yan, G.; Chen, L. Inactivation of lysyl oxidase by β-aminopropionitrile inhibits hypoxia-induced invasion and migration of cervical cancer cells. Oncol. Rep. 2012, 29, 541–548.
  37. Shi, L.; Zhang, N.; Liu, H.; Zhao, L.; Liu, J.; Wan, J.; Wu, W.; Lei, H.; Liu, R.; Han, M. Lysyl oxidase inhibition via β-aminoproprionitrile hampers human umbilical vein endothelial cell angiogenesis and migration in vitro. Mol. Med. Rep. 2018, 17, 5029–5036.
  38. Nilsson, M.; Adamo, H.; Bergh, A.; Bergström, S.H. Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer. Sci. Rep. 2016, 6, 19608.
  39. Li, Q.; Zhu, C.-C.; Ni, B.; Zhang, Z.-Z.; Jiang, S.-H.; Hu, L.-P.; Wang, X.; Zhang, X.-X.; Huang, P.-Q.; Yang, Q.; et al. Lysyl oxidase promotes liver metastasis of gastric cancer via facilitating the reciprocal interactions between tumor cells and cancer associated fibroblasts. EBioMedicine 2019, 49, 157–171.
  40. Ninomiya, G.; Yamada, S.; Hayashi, M.; Takeda, S.; Suenaga, M.; Takami, H.; Kanda, M.; Iwata, N.; Niwa, Y.; Tanaka, C.; et al. Significance of Lysyl oxidase-like 2 gene expression on the epithelial-mesenchymal status of hepatocellular carcinoma. Oncol. Rep. 2018, 39, 2664–2672.
  41. Liu, S.B.; Ikenaga, N.; Peng, Z.; Sverdlov, D.Y.; Greenstein, A.; Smith, V.; Schuppan, D.; Popov, Y.V. Lysyl oxidase activity contributes to collagen stabilization during liver fibrosis progression and limits spontaneous fibrosis reversal in mice. FASEB J. 2015, 30, 1599–1609.
  42. Wang, X.; Huang, W.; Liu, G.; Cai, W.; Millard, R.W.; Wang, Y.; Chang, J.; Peng, T.; Fan, G.-C. Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. J. Mol. Cell. Cardiol. 2014, 74, 139–150.
  43. Li, J.; Liu, K.; Liu, Y.; Xu, Y.; Zhang, F.; Yang, H.; Liu, J.; Pan, T.; Chen, J.; Wu, M.; et al. Exosomes mediate the cell-to-cell transmission of IFN-α-induced antiviral activity. Nat. Immunol. 2013, 14, 793–803.
  44. Kulshreshtha, A.; Ahmad, T.; Agrawal, A.; Ghosh, B. Proinflammatory role of epithelial cell–derived exosomes in allergic airway inflammation. J. Allergy Clin. Immunol. 2013, 131, 1194–1203.e14.
  45. Kosaka, N.; Iguchi, H.; Yoshioka, Y.; Takeshita, F.; Matsuki, Y.; Ochiya, T. Secretory mechanisms and intercellular transfer of MicroRNAs in living cells. J. Biol. Chem. 2010, 285, 17442–17452.
  46. Li, R.; Wang, Y.; Zhang, X.; Feng, M.; Ma, J.; Li, J.; Yang, X.; Fang, F.; Xia, Q.; Zhang, Z.; et al. Exosome-mediated secretion of LOXL4 promotes hepatocellular carcinoma cell invasion and metastasis. Mol. Cancer 2019, 18, 1–19.
  47. Shao, J.; Lu, J.; Zhu, W.; Yu, H.; Jing, X.; Wang, Y.; Wang, X.; Wang, X. Derepression of LOXL4 inhibits liver cancer growth by reactivating compromised p53. Cell Death Differ. 2019, 26, 2237–2252.
  48. Rodriguez, H.M.; Vaysberg, M.; Mikels, A.; McCauley, S.; Velayo, A.C.; Garcia, C.; Smith, V. Modulation of Lysyl Oxidase-like 2 Enzymatic Activity by an Allosteric Antibody Inhibitor. J. Biol. Chem. 2010, 285, 20964–20974.
  49. Barry-Hamilton, V.; Spangler, R.; Marshall, D.; McCauley, S.A.; Rodriguez, H.M.; Oyasu, M.; Mikels, A.; Vaysberg, M.; Ghermazien, H.; Wai, C.; et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat. Med. 2010, 16, 1009–1017.
  50. Muir, A.J.; Levy, C.; Janssen, H.L.; Montano-Loza, A.J.; Shiffman, M.L.; Caldwell, S.; Luketic, V.; Ding, D.; Jia, C.; McColgan, B.J.; et al. Simtuzumab for Primary Sclerosing Cholangitis: Phase 2 Study Results With Insights on the Natural History of the Disease. Hepatology 2019, 69, 684–698.
  51. Schilter, H.C.; Findlay, A.D.; Perryman, L.; Yow, T.T.; Moses, J.; Zahoor, A.; Turner, C.I.; Deodhar, M.; Foot, J.S.; Zhou, W.; et al. The lysyl oxidase like 2/3 enzymatic inhibitor, PXS-5153A, reduces crosslinks and ameliorates fibrosis. J. Cell. Mol. Med. 2018, 23, 1759–1770.
  52. Hutchinson, J.H.; Rowbottom, M.W.; Lonergan, D.; Darlington, J.; Prodanovich, P.; King, C.D.; Evans, J.F.; Bain, G. Small Molecule Lysyl Oxidase-like 2 (LOXL2) Inhibitors: The Identification of an Inhibitor Selective for LOXL2 over LOX. ACS Med. Chem. Lett. 2017, 8, 423–427.
  53. Fan, Z.; Zheng, W.; Li, H.; Wu, W.; Liu, X.; Sun, Z.; Hu, H.; Du, L.; Jia, Q.; Liu, Q. LOXL2 upregulates hypoxia-inducible factor-1α signaling through Snail-FBP1 axis in hepatocellular carcinoma cells. Oncol. Rep. 2020, 43, 1641–1649.
  54. Leung, L.M.H.; Niculescu-Duvaz, D.; Smithen, D.; Lopes, F.; Callens, C.; McLeary, R.; Saturno, G.; Davies, L.; Aljarah, M.; Brown, M.; et al. Anti-metastatic Inhibitors of Lysyl Oxidase (LOX): Design and Structure-Activity Relationships. J. Med. Chem. 2019, 62, 5863–5884.
  55. Smithen, D.A.; Leung, L.M.H.; Challinor, M.; Lawrence, R.; Tang, H.; Niculescu-Duvaz, D.; Pearce, S.P.; McLeary, R.; Lopes, F.; Aljarah, M.; et al. 2-Aminomethylene-5-sulfonylthiazole Inhibitors of Lysyl Oxidase (LOX) and LOXL2 Show Significant Efficacy in Delaying Tumor Growth. J. Med. Chem. 2019, 63, 2308–2324.
  56. Xu, Y.; Wang, X.; Huang, Y.; Ma, Y.; Jin, X.; Wang, H.; Wang, J. Inhibition of lysyl oxidase expression by dextran sulfate affects invasion and migration of gastric cancer cells. Int. J. Mol. Med. 2018, 42, 2737–2749.
  57. Chen, X.; Kou, Y.; Lu, Y.; Pu, Y. Salidroside ameliorated hypoxia-induced tumorigenesis of BxPC-3 cells via downregulating hypoxia-inducible factor (HIF)-1α and LOXL2. J. Cell. Biochem. 2019, 121, 165–173.
  58. Wang, Y.; Xu, X.; Zhao, P.; Tong, B.; Wei, Z.; Dai, Y. Escin Ia suppresses the metastasis of triple-negative breast cancer by inhibiting epithelial-mesenchymal transition via down-regulating LOXL2 expression. Oncotarget 2016, 7, 23684–23699.
  59. Morisawa, A.; Okui, T.; Shimo, T.; Ibaragi, S.; Okusha, Y.; Ono, M.; Nguyen, T.T.H.; Hassan, N.M.M.; Sasaki, A. Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma. Int. J. Oncol. 2018, 52, 989–999.
  60. Lou, W.; Liu, J.; Gao, Y.; Zhong, G.; Ding, B.; Xu, L.; Fan, W. MicroRNA regulation of liver cancer stem cells. Am. J. Cancer Res. 2018, 8, 1126–1141.
  61. Wong, C.C.-L.; Tse, A.P.-W.; Huang, Y.-P.; Zhu, Y.-T.; Chiu, D.K.-C.; Lai, R.K.-H.; Au, S.L.-K.; Kai, A.K.-L.; Lee, J.M.-F.; Wei, L.L.; et al. Lysyl oxidase-like 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma. Hepatology 2014, 60, 1645–1658.
  62. Fukumoto, I.; Kikkawa, N.; Matsushita, R.; Kato, M.; Kurozumi, A.; Nishikawa, R.; Goto, Y.; Koshizuka, K.; Hanazawa, T.; Enokida, H.; et al. Tumor-suppressive microRNAs (miR-26a/b, miR-29a/b/c and miR-218) concertedly suppressed metastasis-promoting LOXL2 in head and neck squamous cell carcinoma. J. Hum. Genet. 2016, 61, 109–118.
  63. Kato, M.; Kurozumi, A.; Goto, Y.; Matsushita, R.; Okato, A.; Nishikawa, R.; Fukumoto, I.; Koshizuka, K.; Ichikawa, T.; Seki, N. Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer. J. Hum. Genet. 2016, 62, 123–132.
  64. Kurozumi, A.; Kato, M.; Goto, Y.; Matsushita, R.; Nishikawa, R.; Okato, A.; Fukumoto, I.; Ichikawa, T.; Seki, N. Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma. Int. J. Oncol. 2016, 48, 1837–1846.
  65. Saatci, O.; Kaymak, A.; Raza, U.; Ersan, P.G.; Akbulut, O.; Banister, C.E.; Sikirzhytski, V.; Tokat, U.M.; Aykut, G.; Ansari, S.A.; et al. Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer. Nat. Commun. 2020, 11, 1–17.
  66. Boufraqech, M.; Nilubol, N.; Zhang, L.; Gara, S.K.; Sadowski, S.M.; Mehta, A.; He, M.; Davis, S.; Dreiling, J.; Copland, J.A.; et al. miR30a Inhibits LOX Expression and Anaplastic Thyroid Cancer Progression. Cancer Res. 2015, 75, 367–377.
  67. Mizuno, K.; Seki, N.; Mataki, H.; Matsushita, R.; Kamikawaji, K.; Kumamoto, T.; Takagi, K.; Goto, Y.; Nishikawa, R.; Kato, M.; et al. Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma. Int. J. Oncol. 2016, 48, 450–460.
  68. Kamikawaji, K.; Seki, N.; Watanabe, M.; Mataki, H.; Kumamoto, T.; Takagi, K.; Mizuno, K.; Inoue, H. Regulation of LOXL2 and SERPINH1 by antitumor microRNA-29a in lung cancer with idiopathic pulmonary fibrosis. J. Hum. Genet. 2016, 61, 985–993.
  69. Ye, M.-F.; Zhang, J.-G.; Guo, T.-X.; Pan, X.-J. MiR-504 inhibits cell proliferation and invasion by targeting LOXL2 in non small cell lung cancer. Biomed. Pharmacother. 2018, 97, 1289–1295.
  70. Duan, Z.; Li, L.; Li, Y. Involvement of miR-30b in kynurenine-mediated lysyl oxidase expression. J. Physiol. Biochem. 2019, 75, 135–142.
  71. Zhang, Y.; Jiang, W.; Yang, J.; Huang, J.; Kang, G.; Hu, H.; Xie, S. Downregulation of lysyl oxidase-like 4 LOXL4 by miR-135a-5p promotes lung cancer progression in vitro and in vivo. J. Cell. Physiol. 2019, 234, 18679–18687.
  72. Xie, S.; Liu, G.; Huang, J.; Hu, H.; Jiang, W. miR-210 promotes lung adenocarcinoma proliferation, migration, and invasion by targeting lysyl oxidase-like 4. J. Cell. Physiol. 2019, 234, 14050–14057.
Subjects: Others
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to :
View Times: 547
Revisions: 2 times (View History)
Update Date: 07 Jan 2021
Video Production Service