Diverse molecular functions of aspartate β‑hydroxylase in cancer (Review)

Oncol Rep. 2020 Dec;44(6):2364-2372. doi: 10.3892/or.2020.7792. Epub 2020 Oct 6.

Abstract

Aspartate/asparagine β‑hydroxylase (AspH) is a type II transmembrane protein that catalyzes the post‑translational hydroxylation of definite aspartyl and asparaginyl residues in epidermal growth factor‑like domains of substrates. In the last few decades, accumulating evidence has indicated that AspH expression is upregulated in numerous types of human malignant cancer and is associated with poor survival and prognosis. The AspH protein aggregates on the surface of tumor cells, which contributes to inducing tumor cell migration, infiltration and metastasis. However, small‑molecule inhibitors targeting hydroxylase activity can markedly block these processes, both in vitro and in vivo. Immunization of tumor‑bearing mice with a phage vaccine fused with the AspH protein can substantially delay tumor growth and progression. Additionally, AspH antigen‑specific CD4+ and CD8+ T cells were identified in the spleen of tumor‑bearing mice. Therefore, these agents may be used as novel strategies for cancer treatment. The present review summarizes the current progress on the underlying mechanisms of AspH expression in cancer development.

Keywords: aspartate β-hydroxylase; tumor; small-molecule inhibitors; Notch pathway; PI3K pathway; immunotherapy.

Publication types

  • Review

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Calcium-Binding Proteins / antagonists & inhibitors
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / immunology
  • Calcium-Binding Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Furans / pharmacology
  • Furans / therapeutic use
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics*
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / immunology
  • Mixed Function Oxygenases / metabolism
  • Muscle Proteins / antagonists & inhibitors
  • Muscle Proteins / genetics*
  • Muscle Proteins / immunology
  • Muscle Proteins / metabolism
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / immunology
  • Neoplasm Invasiveness / pathology
  • Neoplasms / genetics*
  • Neoplasms / immunology
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Prognosis
  • Sulfonic Acids / pharmacology
  • Sulfonic Acids / therapeutic use
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Calcium-Binding Proteins
  • Furans
  • MO-I-1100
  • Membrane Proteins
  • Muscle Proteins
  • Sulfonic Acids
  • Mixed Function Oxygenases
  • ASPH protein, human