2. Academic Validation
  3. USP13 depletion sensitizes colorectal cancer cells to necroptosis by destabilizing cIAP2 proteins

USP13 depletion sensitizes colorectal cancer cells to necroptosis by destabilizing cIAP2 proteins

  • Cell Death Differ. 2025 Oct 22. doi: 10.1038/s41418-025-01595-4.
Yeon Jung Kim # 1,  Tanuza Das # 2,  Jinyoung Park 3 4,  Inah Hwang 1 5,  Eunice EunKyeong Kim 2,  Eun Joo Song 6 7
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.
  • 2 Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
  • 3 Center for Advanced Biomolecular Recognition, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
  • 4 Division of Bio-Medical Science and Technology, KIST-School, University of Science and Technology (UST), Seoul, Republic of Korea.
  • 5 Graduate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul, Republic of Korea.
  • 6 Graduate School of Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea. esong@ewha.ac.kr.
  • 7 Graduate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul, Republic of Korea. esong@ewha.ac.kr.
  • # Contributed equally.
PMID: 41125793 DOI: 10.1038/s41418-025-01595-4
Abstract

Ubiquitin removal by deubiquitinating Enzymes (DUBs) is a crucial cellular process. Among the DUBs, Ubiquitin-Specific Protease 13 (USP13) is overexpressed in multiple cancers and is associated with tumorigenesis and poor prognosis. However, its involvement in the cell death pathway is poorly understood. Thus, we describe the novel function of USP13 as a crucial regulator of Necroptosis. USP13 interacts with cellular IAP2 (cIAP2), stabilizing cIAP2 proteins in colorectal Cancer (CRC) cells. The TCGA-COAD and GEO databases revealed USP13 upregulation in CRC patients and its association with poor clinical outcomes. The loss of USP13 significantly potentiates TNF-α/SMAC mimetic birinapant/pan-caspase inhibitor Z-VAD-FMK (TBZ)-induced Necroptosis in CRC cells and diminishes tumor growth in a xenograft model. Thereby, USP13 may serve as a potential therapeutic target for Anticancer treatment of CRC.

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