Authors
Peng Hao, Jiale Wan, Zhangyu Guo, Zhenge Zhang, Guoyun Hu, Yongkang Liu, Hu Lei, Yingli Wu, Hao Luo
Published in
Biochimica et biophysica acta. Reviews on cancer. Pages 189689. Aug 18, 2026. Epub Aug 18, 2026.
Abstract
Ubiquitin-specific protease 2 (USP2), a pivotal member of the deubiquitinating enzyme family, has emerged as a critical but context-dependent regulator in cancer, exhibiting paradoxical tumor-suppressive and oncogenic functions. This duality is governed by its ability to stabilize specific substrate proteins, thereby modulating central signaling hubs including the p53, Wnt/β-catenin, PI3K/Akt, and cell cycle networks. Through these axes, USP2 profoundly influences hallmark cancer phenotypes such as sustained proliferation, metabolic reprogramming, metastatic progression, immune evasion, and therapy resistance. This review systematically synthesizes the mechanistic roles of USP2 across various cancers, highlighting its function as a double-edged sword. We detail how specific interactions between USP2 and its substrates dictate its pro-tumorigenic or anti-tumorigenic outcomes, depending on the tissue and microenvironment. Furthermore, we comprehensively evaluate the landscape of emerging USP2 inhibitors, discussing their therapeutic potential and the significant challenges posed by USP2's functional duality, substrate promiscuity, and isoform diversity. Targeting USP2 presents a promising yet intricate avenue for cancer therapy, necessitating future research focused on patient stratification, combination strategies, and the development of context-specific inhibitors.
PMID:
42612736
Bibliographic data and abstract were imported from PubMed on 19 Aug 2026.
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