Table 1.
Summary of USP family members and corresponding mechanisms
| USP Family Member | Related Signaling Pathway/Axis | Substrate/Downstream Molecule | Effect/Outcome | Experimental Methods/Key Findings |
|---|---|---|---|---|
| USP7(Su et al. 2024) | p53 stabilization | p53 | Inhibit tumorigenesis | Removal of p53 ubiquitin chains |
| Stabilization of other oncoproteins | Oncoproteins | Promote tumor progression | - | |
| USP22(Ning et al. 2022; Li et al. 2022) | Regulation of protein stability | Multiple targets | Influence cancer stem cell properties | - |
| - | ABCC1 | Sorafenib resistance | USP22 knockout reduces ABCC1 expression; IHC shows positive correlation in resistant samples | |
| - | E2F6 | Activate PKB, promote HCC progression | USP22 knockout upregulates DUSP1, inhibits PKB activity | |
| USP28(Sun et al. 2022) | Wnt signaling pathway | TCF7L2 | Promote tumorigenesis | Inhibitor treatment in xenograft model reduces tumor size and TCF7L2 protein |
| USP10(Yuan et al. 2020) | TGF-β pathway | Smad4 | Promote HCC cell migration | Inhibits Smad4 ubiquitination and degradation |
| USP14(Xu et al. 2024) | PAK1-ERK1/2 axis | CIB1 | Maintain lenvatinib resistance | USP14 knockout alters CIB1 expression; AAV-shCIB1 restores drug sensitivity |
| USP20(Park et al. 2013) | HIF-1α pathway | HIF-1α | Promote tumor angiogenesis | Inhibits HIF-1α ubiquitination and degradation |
| USP8(Tang et al. 2023a) | Wnt/β-catenin/GPX4 axis | β-catenin | Inhibit ferroptosis | Knockout increases ROS, decreases GSH and GPX4 |
| - | OGT, SLC7A11 | Inhibit ferroptosis | Stabilizes OGT and SLC7A11, enhances cystine uptake, reduces lipid ROS | |
| USP1(Wang et al. 2022a) | - | c-Kit | Promote HCC progression, enhance lenvatinib toxicity | Knockout of c-Kit reverses USP1 oncogenicity |
| USP2a(Xiong et al. 2021) | - | RAB1A | Promote proliferation, migration, invasion | Inhibits RAB1A degradation |
| USP27(Zou et al. 2022) | - | SETD3 | Promote migration and invasion | Inhibits SETD3 degradation |
| USP40(Wu et al. 2024) | - | CLDN1 | Promote proliferation, migration, stemness | Inhibits CLDN1 ubiquitination |
| USP11(Qiao et al. 2021) | - | KLF4 (K63-linked) | Promote proliferation and tumorigenesis | Disrupts K63 chains, leading to KLF4 degradation |
| E2F1-USP11 positive feedback loop | E2F1 | Inhibit autophagy, promote HCC progression | Stabilizes E2F1, activates ERK/mTOR pathway | |
| CYLD (Regamey et al. 2003; Minderman et al. 2023) | NF-κB pathway | TRAF2, TRAF6, TRIP, TAK1 | Inhibit NF-κB activation | Interacts with TRIP and TRAF2 to stabilize TRIP, suppress NF-κB hyperactivation |