TY - JOUR
T1 - USP13 depletion sensitizes colorectal cancer cells to necroptosis by destabilizing cIAP2 proteins
AU - Kim, Yeon Jung
AU - Das, Tanuza
AU - Park, Jinyoung
AU - Hwang, Inah
AU - Kim, Eunice Eun Kyeong
AU - Song, Eun Joo
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare 2025.
PY - 2025
Y1 - 2025
N2 - 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. (Figure presented.)
AB - 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. (Figure presented.)
UR - https://www.scopus.com/pages/publications/105019625754
U2 - 10.1038/s41418-025-01595-4
DO - 10.1038/s41418-025-01595-4
M3 - Article
AN - SCOPUS:105019625754
SN - 1350-9047
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
ER -
