Work

Dual faces of USP10 in breast cancer: Oncogenic driver, tumor suppressor, and emerging therapeutic target

Year: 2025

Type: article

Abstract: Ubiquitin-specific protease 10 (USP10) has emerged as a pivotal yet paradoxical regulator in breast cancer (BC) pathogenesis, exhibiting context-dependent duality as both an oncogenic driver and tumor suppressor. This review synthesizes recent advances in elucidating USP10's mechanistic roles in modulating oncogenic signaling, tumor immunity, and therapeutic resistance, with a central focus on its paradoxical dual regulation. USP10 stabilizes tumor-promoting substrates to drive the malignant phenotypes, while also exerting tumor-suppressive effects. Clinically, USP10 overexpression correlates with aggressive phenotypes and poor prognosis. Therapeutically, USP10 inhibition synergizes with Poly ADP-ribose polymerase (PARP) inhibitors and antibody-drug conjugates (ADCs), effectively suppressing tumor growth in preclinical models. Key challenges include resolving USP10's functional dichotomy across BC subtypes, developing isoform-selective inhibitors, and overcoming resistance mechanisms. Future directions emphasize spatial proteomics to map USP10 interactomes in metastatic niches and genetically engineered models for validating synthetic lethality approaches. Collectively, USP10 represents a promising therapeutic target in BC. Its complex, context-dependent role underscores the need for targeted strategies to exploit its functions for precision oncology. • USP10 exhibits context-dependent oncogenic/tumor-suppressive roles in breast cancer via substrate deubiquitination. • USP10 modulates proliferation, metastasis, and immune evasion by targeting key pathways. • USP10 inhibition synergizes with PARP inhibitors, ADCs, and chemotherapy in preclinical breast cancer models. • USP10 represents a promising precision oncology target requiring subtype-specific strategies.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2025.118916

Authors: Cong Fan, Jiajia Wang, Jianing Sun, Mengxuan Li, Jiajun Ding, Haoyi Zi, Shuai Wang, Jian Zhang, Ting Wang

Institutions: Xijing Hospital, Air Force Medical University, Xi'an Honghui Hospital, Xi'an Jiaotong University

Language: English

Topic: Ubiquitin and proteasome pathways

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,610