Emerging potential of ubiquitin-specific proteases and ubiquitin-specific proteases inhibitors in breast cancer treatment

Abstract

Breast cancer is the most frequently diagnosed cancer in women, accounting for 30% of new diagnosing female cancers. Emerging evidence suggests that ubiquitin and ubiquitination played a role in a number of breast cancer etiology and progression processes. As the primary deubiquitinases in the family, ubiquitin-specific peptidases (USPs) are thought to represent potential therapeutic targets. The role of ubiquitin and ubiquitination in breast cancer, as well as the classification and involvement of USPs are discussed in this review, such as USP1, USP4, USP7, USP9X, USP14, USP18, USP20, USP22, USP25, USP37, and USP39. The reported USPs inhibitors investigated in breast cancer were also summarized, along with the signaling pathways involved in the investigation and its study phase. Despite no USP inhibitor has yet been approved for clinical use, the biological efficacy indicated their potential in breast cancer treatment. With the improvements in phenotypic discovery, we will know more about USPs and USPs inhibitors, developing more potent and selective clinical candidates for breast cancer.

Keywords: Breast cancer; Review; USPs inhibitors; Ubiquitin-specific proteases.

Figure 1

Graphaic figure of the review. USPs: Ubiquitin-specific peptidases.

Figure 2

Crystal structure of ubiquitin-specific peptidases. A: Ubiquitin-specific peptidases (USP) 7 in complex with a novel inhibitor; B: Crystal structure of the catalytic domain of human USP9X; C: Structure of USP14; D: Structure of human USP25.

Figure 3

Ubiquitin-specific peptidases inhibitors. USPs: Ubiquitin-specific peptidases; 6-TG: 6-thioguanine.