Emerging roles of the HECT E3 ubiquitin ligases in gastric cancer

Gastric cancer (GC) is one of the most pernicious gastrointestinal tumors with extraordinarily high incidence and mortality. Ubiquitination modification of cellular signaling proteins has been shown to play important roles in GC tumorigenesis, progression, and prognosis. The E3 ubiquitin ligase is the crucial enzyme in the ubiquitination reaction and determines the specificity of ubiquitination substrates, and thus, the cellular effects. The HECT E3 ligases are the second largest E3 ubiquitin ligase family characterized by containing a HECT domain that has E3 ubiquitin ligase activity. The HECT E3 ubiquitin ligases have been found to engage in GC progression. However, whether HECT E3 ligases function as tumor promoters or tumor suppressors in GC remains controversial. In this review, we will focus on recent discoveries about the role of the HECT E3 ubiquitin ligases, especially members of the NEDD4 and other HECT E3 ligase subfamilies, in GC.

Automated summary

Gastric cancer is a highly malignant gastrointestinal tumor with high incidence and mortality. Ubiquitination modification of cellular signaling proteins plays an important role in gastric cancer tumorigenesis, progression, and prognosis. The HECT E3 ubiquitin ligases have been found to be involved in gastric cancer progression, but their role as tumor promoters or tumor suppressors in gastric cancer is controversial. This review focuses on recent discoveries about the role of HECT E3 ubiquitin ligases, especially members of the NEDD4 and other HECT E3 ligase subfamilies, in gastric cancer.