USP2 in cancer: a double-edged sword and therapeutic target

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Ubiquitin-specific protease 2 (USP2) is a deubiquitinating enzyme with context-dependent roles in cancer.
• USP2's functions are dictated by its stabilization of specific substrate proteins.
• It modulates key signaling pathways like p53, Wnt/β-catenin, PI3K/Akt, and cell cycle regulation.

Purpose of the Study:

• To systematically review the mechanistic roles of USP2 in various cancers.
• To highlight USP2's dual function as a tumor suppressor and oncogene.
• To evaluate emerging USP2 inhibitors and associated therapeutic challenges.

Main Methods:

• Systematic literature review of USP2's mechanistic roles in cancer.
• Analysis of USP2's substrate interactions and their impact on signaling pathways.
• Evaluation of current USP2 inhibitor landscape and therapeutic strategies.

Main Results:

• USP2 influences cancer hallmarks including proliferation, metabolism, metastasis, immune evasion, and therapy resistance.
• USP2's pro- or anti-tumorigenic effects are determined by substrate interactions, tissue type, and microenvironment.
• Emerging USP2 inhibitors show therapeutic potential but face challenges due to USP2's functional duality, substrate promiscuity, and isoform diversity.

Conclusions:

• Targeting USP2 is a promising but complex cancer therapy strategy.
• Future research should focus on patient stratification, combination therapies, and context-specific inhibitors.
• Understanding USP2's substrate-specific functions is crucial for effective therapeutic development.