Diverse molecular functions of aspartate β-hydroxylase in cancer

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.