Roles of Lysyl Oxidase Family Members in the Tumor Microenvironment and Progression of Liver Cancer

Int J Mol Sci. 2020 Dec 21;21(24):9751. doi: 10.3390/ijms21249751.


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. We herein review the clinical value and novel biological roles of LOX family members in tumor progression and the TME of liver cancers. In addition, we highlight recent insights into their mechanisms and their potential involvement in the development of target therapy for liver cancer.

Keywords: cholangiocarcinoma; hepatocellular carcinoma; liver cancer; lysyl oxidase family members; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Progression
  • Humans
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology*
  • Protein-Lysine 6-Oxidase / classification
  • Protein-Lysine 6-Oxidase / metabolism*
  • Tumor Microenvironment / immunology*


  • Protein-Lysine 6-Oxidase